A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase 2A Study to Assess the Efficacy of RO5459072 in Patients With Primary Sjogren's Syndrome

Source: Publicly Available
Added: 16 Jun 2026
Contributor: System
Produced by: USDM Template v12 12.0.0

Phase II Trial Interventional Study v1.0 USDM v4.0.0

Sponsor: Sponsor Organization
Protocol ID: BP30037
Identifier: NCT02701985

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Synopsis

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase 2A Study to Assess the Efficacy of RO5459072 in Patients With Primary Sjogren's Syndrome

Study

Study type: Interventional Study
Phase: Phase II Trial
Therapeutic area: Rheumatology
Protocol version: 1.0

Design

Design: Not stated
Model: Single Group Study
Blinding: Open Label Study
Intent: Treatment Study
Arms: 1
Epochs: 3

Participants

Population: Study population
Planned enrolment: 70
Sex: Both
Age: 18 Year to 75 Year
Healthy participants: Patients only

Key dates

Protocol Approval: 01 Jan 2024

Objectives and endpoints

Primary

To investigate the effects of RO5459072 treatment on disease activity and symptoms of primary Sjögren’s syndrome.

Primary
Proportion of patients showing a clinically relevant decrease in ESSDAI score from baseline after 12 weeks.

Secondary

To investigate the effects of RO5459072 treatment on:quality of life measures.auto-antibody concentrations.pharmacodynamic measures of exocrine gland function.

Secondary
Proportion of individuals showing a clinically relevant decrease in ESSPRI score after 12 weeks where a clinically relevant decrease in ESSPRI score is defined as a decrease of ≥ 1 point.
Secondary
Change from baseline in ESSDAI, ESSPRI and SF-36 scores after 12 weeks.
Secondary
Change from baseline in each of the individual components of the ESSPRI (dryness, fatigue and pain) after 12 weeks.

Secondary

To collect samples for population modelling of RO5459072 pharmacokinetics.

Secondary
RO5459072 plasma concentration data will be pooled with data from other studies (Study WP29542 and Study BP29772) for population pharmacokinetic modelling. The modelling results will be reported separately.

Secondary

To investigate the safety and tolerability of RO5459072 treatment.

Secondary
The incidence and severity of AEs.
Secondary
The incidence of SAEs or withdrawals because of AEs.
Secondary
The incidence of out-of-reference-range values for vital signs and ECGs, and laboratory tests.
Secondary
Change from baseline in vital signs and ECGs, and laboratory tests by visit.

Exploratory

To investigate the effects of RO5459072 treatment on:cathepsin S enzyme mass and activity.sub-populations of circulating white blood cells.biomarkers connected to Sjögren’s syndrome.biomarkers of extracellular matrix degradation.

Exploratory
Comparisons of the performance of alternative composite endpoints (e.g., Sjögren’s response index [SSRI-30]) as predictive markers of drug treatment response.

Exploratory

To explore the influence of covariates on the effects of RO5459072 treatment.

Exploratory
Change from Week 12 to follow-up for ESSDAI, ESSPRI and SF-36 scores in each treatment group.

Exploratory

To explore alternative composite endpoints as measures for evaluating effects of drug treatment.

Exploratory
Comparisons of drug treatment effects between genotypes.

Exploratory

To explore the effects of RO5459072 treatment on the use of concomitant medications.

Exploratory
Patterns of use of selected concomitant medications.

Exploratory

To explore the occurrence of acute rebound phenomena on disease activity and symptoms following discontinuation of study drug treatment.

Exploratory
Change from Week 12 to follow-up for ESSDAI, ESSPRI and SF-36 scores in each treatment group.

Eligibility

Inclusion 7

1
Males and females 18 to 75 years of age, inclusive.
2
Patient willing to give written informed consent and to comply with the study procedures and restrictions.
3
Primary Sjögren's syndrome diagnosed previously according to the revised American-European Consensus Group (AECG) criteria.
4
European League against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) score ≥ 5.
5
EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score ≥ 5.
6
Elevated serum titers at screening of anti-Sjögren's-syndrome-related antigen A (anti-SSA) and/or anti-SSB antibodies at screening.
7
Negative pregnancy test at screening and baseline (women only), and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation

Exclusion 15

8
A diagnosis of secondary Sjögren's syndrome according to the revised AECG criteria.
9
Severe complications of Sjögren's syndrome, such as vasculitis with renal, neurologic or cardiac involvement; interstitial lung disease and severe myositis,
10
Systemic immunosuppressant therapy (e.g., abatacept, azathioprine, ciclosporin, etanercept, tofacitinib), cyclophosphamide or B cell depleting therapy (e.g., rituximab anti-CD20 therapy) within 6...
11
Corticosteroid therapy exceeding 7.5 mg prednisone equivalents per day.
12
Mechanically stimulated whole salivary flow rate at baseline of < 0.1 mL/min.
13
A positive test result for hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV), or tuberculosis, or any other active viral, fungal, yeast or bacterial infection at the...
14
A history of recurring or chronic infections, any other indication of reduced immune function considered to be clinically significant by the Investigator, or any other underlying conditions which...
15
A history of lymphoma, myeloma (monoclonal hypergammaglobulinemia) or monoclonal gammopathy of unknown significance (MGUS), or any other malignancies within the past 5 years (except basal cell or...
16
A diagnosis of fibromyalgia, or a diagnosis of significant depression or anxiety that in the opinion of the investigator would confound the interpretation of the study results.
17
Severe renal impairment (e.g., estimated glomerular filtration rate < 30 mL/min), moderate or severe hepatic impairment (e.g., Child-Pugh B or C) or other clinically significant hepatic disease...
18
Current or a history of severe, progressive or uncontrolled hematologic, gastrointestinal, endocrine, pulmonary, cardiac, or neurologic disease, or any other concomitant disease or condition or...
19
Participation in an investigational drug or device study within 3 months prior to screening.
20
Inability to comply with the study protocol for any other reason.
21
Women who are lactating, breastfeeding or planning to nurse.
22
Using other prohibited medication (moderate or potent inhibitors of CYP3A4; strong inducers of CYP3A4; strong inhibitors of the transporter P-glycoprotein [P-gp]; sensitive substrates of CYP3A4...

No order is declared for these criteria, which USDM permits. Grouped by inclusion and exclusion, then by criterion number.

Study design

What each arm receives in each epoch of the study.
Arm	Screening & Baseline Screening	Treatment	Follow Up
Main Protocol Treatment Arm	—	—	—

Interventions

Intervention 1

RO5459072 100mg (Route: Oral)

Placebo

Placebo (Route: Oral)

Schedule of Activities

8 visits 56 activities Entry: Subject enrolled in study arm

Schedule of Activities — 8 visits

Activities by visit. A dot marks a visit at which the activity takes place.
Activity	Screening & Baseline		Treatment				Follow Up
Visit	8 Main Day 42	1 Main Day 1	14 Main Day 8	42 Main Day 63	63 Main Day 5	84 Main Day 14	14 Main Day 14	Unknown Main Day 84
From previous visit	◆ Screening & Baseline Day -1.0		+1 day	+1 day	+1 day	+1 day	+1 day	+1 day
Sjogrens Syndrome-B ENA [Unit/Vol] by Immunoassay, Serum	Sjogrens Syndrome-B ENA [Unit/Vol] by Immunoassay, Serum at 8	Sjogrens Syndrome-B ENA [Unit/Vol] by Immunoassay, Serum at 1		Sjogrens Syndrome-B ENA [Unit/Vol] by Immunoassay, Serum at 42		Sjogrens Syndrome-B ENA [Unit/Vol] by Immunoassay, Serum at 84	Sjogrens Syndrome-B ENA [Unit/Vol] by Immunoassay, Serum at 14	Sjogrens Syndrome-B ENA [Unit/Vol] by Immunoassay, Serum at Unknown
Medical History, General (Lifetime)	Medical History, General (Lifetime) at 8
Cryoglobulin IgA+IgG+IgM+C3 Panel, Serum	Cryoglobulin IgA+IgG+IgM+C3 Panel, Serum at 8	Cryoglobulin IgA+IgG+IgM+C3 Panel, Serum at 1		Cryoglobulin IgA+IgG+IgM+C3 Panel, Serum at 42		Cryoglobulin IgA+IgG+IgM+C3 Panel, Serum at 84	Cryoglobulin IgA+IgG+IgM+C3 Panel, Serum at 14	Cryoglobulin IgA+IgG+IgM+C3 Panel, Serum at Unknown
IRT-Eligibility Checklist	IRT-Eligibility Checklist at 8	IRT-Eligibility Checklist at 1
C Reactive Protein [Mass/Vol] by HSM, Serum or Plasma	C Reactive Protein [Mass/Vol] by HSM, Serum or Plasma at 8	C Reactive Protein [Mass/Vol] by HSM, Serum or Plasma at 1	C Reactive Protein [Mass/Vol] by HSM, Serum or Plasma at 14	C Reactive Protein [Mass/Vol] by HSM, Serum or Plasma at 42	C Reactive Protein [Mass/Vol] by HSM, Serum or Plasma at 63	C Reactive Protein [Mass/Vol] by HSM, Serum or Plasma at 84	C Reactive Protein [Mass/Vol] by HSM, Serum or Plasma at 14	C Reactive Protein [Mass/Vol] by HSM, Serum or Plasma at Unknown
Rheumatoid Factor [Presence], Serum	Rheumatoid Factor [Presence], Serum at 8	Rheumatoid Factor [Presence], Serum at 1		Rheumatoid Factor [Presence], Serum at 42		Rheumatoid Factor [Presence], Serum at 84	Rheumatoid Factor [Presence], Serum at 14	Rheumatoid Factor [Presence], Serum at Unknown
Nuclear Ab [Presence], Serum	Nuclear Ab [Presence], Serum at 8	Nuclear Ab [Presence], Serum at 1		Nuclear Ab [Presence], Serum at 42		Nuclear Ab [Presence], Serum at 84	Nuclear Ab [Presence], Serum at 14	Nuclear Ab [Presence], Serum at Unknown
Erythrocyte Sedimentation Rate, Blood		Erythrocyte Sedimentation Rate, Blood at 1	Erythrocyte Sedimentation Rate, Blood at 14	Erythrocyte Sedimentation Rate, Blood at 42		Erythrocyte Sedimentation Rate, Blood at 84
IgG [Mass/Vol], Serum	IgG [Mass/Vol], Serum at 8	IgG [Mass/Vol], Serum at 1		IgG [Mass/Vol], Serum at 42		IgG [Mass/Vol], Serum at 84	IgG [Mass/Vol], Serum at 14	IgG [Mass/Vol], Serum at Unknown
HIV 1+2 Ab [Presence], Serum	HIV 1+2 Ab [Presence], Serum at 8
Sjogrens Syndrome-A ENA [Unit/Vol] by Immunoassay, Serum	Sjogrens Syndrome-A ENA [Unit/Vol] by Immunoassay, Serum at 8	Sjogrens Syndrome-A ENA [Unit/Vol] by Immunoassay, Serum at 1		Sjogrens Syndrome-A ENA [Unit/Vol] by Immunoassay, Serum at 42		Sjogrens Syndrome-A ENA [Unit/Vol] by Immunoassay, Serum at 84	Sjogrens Syndrome-A ENA [Unit/Vol] by Immunoassay, Serum at 14	Sjogrens Syndrome-A ENA [Unit/Vol] by Immunoassay, Serum at Unknown
Prior/Concomitant Medications	Prior/Concomitant Medications at 8
IRT-Randomization		IRT-Randomization at 1
4-β-hydroxycholesterol/Cholesterol [Mass/Vol], Plasma		4-β-hydroxycholesterol/Cholesterol [Mass/Vol], Plasma at 1	4-β-hydroxycholesterol/Cholesterol [Mass/Vol], Plasma at 14	4-β-hydroxycholesterol/Cholesterol [Mass/Vol], Plasma at 42		4-β-hydroxycholesterol/Cholesterol [Mass/Vol], Plasma at 84
12 Lead ECG (Triplicate)	12 Lead ECG (Triplicate) at 8	12 Lead ECG (Triplicate) at 1	12 Lead ECG (Triplicate) at 14	12 Lead ECG (Triplicate) at 42	12 Lead ECG (Triplicate) at 63	12 Lead ECG (Triplicate) at 84	12 Lead ECG (Triplicate) at 14	12 Lead ECG (Triplicate) at Unknown
CBC W Differential Panel by Unspecified Method, Blood	CBC W Differential Panel by Unspecified Method, Blood at 8	CBC W Differential Panel by Unspecified Method, Blood at 1	CBC W Differential Panel by Unspecified Method, Blood at 14	CBC W Differential Panel by Unspecified Method, Blood at 42	CBC W Differential Panel by Unspecified Method, Blood at 63	CBC W Differential Panel by Unspecified Method, Blood at 84	CBC W Differential Panel by Unspecified Method, Blood at 14	CBC W Differential Panel by Unspecified Method, Blood at Unknown
Stimulated Salivary Flow Test		Stimulated Salivary Flow Test at 1	Stimulated Salivary Flow Test at 14	Stimulated Salivary Flow Test at 42		Stimulated Salivary Flow Test at 84
IRT-Investigational Product Dispensation		IRT-Investigational Product Dispensation at 1	IRT-Investigational Product Dispensation at 14	IRT-Investigational Product Dispensation at 42
Desmosine [Mass/Vol], Plasma		Desmosine [Mass/Vol], Plasma at 1	Desmosine [Mass/Vol], Plasma at 14	Desmosine [Mass/Vol], Plasma at 42		Desmosine [Mass/Vol], Plasma at 84
Cytokines Panel, Plasma		Cytokines Panel, Plasma at 1	Cytokines Panel, Plasma at 14	Cytokines Panel, Plasma at 42		Cytokines Panel, Plasma at 84
HCG Beta Subunit (Pregnancy Test) [Presence], Serum	HCG Beta Subunit (Pregnancy Test) [Presence], Serum at 8	HCG Beta Subunit (Pregnancy Test) [Presence], Serum at 1	HCG Beta Subunit (Pregnancy Test) [Presence], Serum at 14	HCG Beta Subunit (Pregnancy Test) [Presence], Serum at 42	HCG Beta Subunit (Pregnancy Test) [Presence], Serum at 63	HCG Beta Subunit (Pregnancy Test) [Presence], Serum at 84	HCG Beta Subunit (Pregnancy Test) [Presence], Serum at 14	HCG Beta Subunit (Pregnancy Test) [Presence], Serum at Unknown
Vital Signs	Vital Signs at 8	Vital Signs at 1	Vital Signs at 14	Vital Signs at 42	Vital Signs at 63	Vital Signs at 84	Vital Signs at 14	Vital Signs at Unknown
Adverse Events	Adverse Events at 8	Adverse Events at 1	Adverse Events at 14	Adverse Events at 42	Adverse Events at 63	Adverse Events at 84	Adverse Events at 14	Adverse Events at Unknown
QuantiFERON-TB Gold Test, Blood	QuantiFERON-TB Gold Test, Blood at 8
HCG Beta Subunit (Pregnancy Test) [Presence], Urine		HCG Beta Subunit (Pregnancy Test) [Presence], Urine at 1	HCG Beta Subunit (Pregnancy Test) [Presence], Urine at 14	HCG Beta Subunit (Pregnancy Test) [Presence], Urine at 42	HCG Beta Subunit (Pregnancy Test) [Presence], Urine at 63	HCG Beta Subunit (Pregnancy Test) [Presence], Urine at 84	HCG Beta Subunit (Pregnancy Test) [Presence], Urine at 14	HCG Beta Subunit (Pregnancy Test) [Presence], Urine at Unknown
EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)	EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at 8	EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at 1	EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at 14	EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at 42	EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at 63	EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at 84	EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at 14	EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at Unknown
36-Item Short Form Survey (SF-36)		36-Item Short Form Survey (SF-36) at 1		36-Item Short Form Survey (SF-36) at 42		36-Item Short Form Survey (SF-36) at 84
EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI)	EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at 8	EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at 1		EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at 42		EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at 84	EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at 14	EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at Unknown
Whole mRNA Transcriptome Sequence Analysis, Blood		Whole mRNA Transcriptome Sequence Analysis, Blood at 1	Whole mRNA Transcriptome Sequence Analysis, Blood at 14	Whole mRNA Transcriptome Sequence Analysis, Blood at 42		Whole mRNA Transcriptome Sequence Analysis, Blood at 84
Creatine Kinase [Act/Vol], Serum or Plasma	Creatine Kinase [Act/Vol], Serum or Plasma at 8	Creatine Kinase [Act/Vol], Serum or Plasma at 1	Creatine Kinase [Act/Vol], Serum or Plasma at 14	Creatine Kinase [Act/Vol], Serum or Plasma at 42	Creatine Kinase [Act/Vol], Serum or Plasma at 63	Creatine Kinase [Act/Vol], Serum or Plasma at 84	Creatine Kinase [Act/Vol], Serum or Plasma at 14	Creatine Kinase [Act/Vol], Serum or Plasma at Unknown
Complement C3 and C4 Panel [Mass/Vol], Serum or Plasma	Complement C3 and C4 Panel [Mass/Vol], Serum or Plasma at 8	Complement C3 and C4 Panel [Mass/Vol], Serum or Plasma at 1	Complement C3 and C4 Panel [Mass/Vol], Serum or Plasma at 14	Complement C3 and C4 Panel [Mass/Vol], Serum or Plasma at 42	Complement C3 and C4 Panel [Mass/Vol], Serum or Plasma at 63	Complement C3 and C4 Panel [Mass/Vol], Serum or Plasma at 84	Complement C3 and C4 Panel [Mass/Vol], Serum or Plasma at 14	Complement C3 and C4 Panel [Mass/Vol], Serum or Plasma at Unknown
Body Weight	Body Weight at 8						Body Weight at 14	Body Weight at Unknown
Concomitant Medications		Concomitant Medications at 1	Concomitant Medications at 14	Concomitant Medications at 42	Concomitant Medications at 63	Concomitant Medications at 84	Concomitant Medications at 14	Concomitant Medications at Unknown
Investigational Product Return				Investigational Product Return at 42		Investigational Product Return at 84		Investigational Product Return at Unknown
BAFF-R Cells/100 CD19 Cells, Blood		BAFF-R Cells/100 CD19 Cells, Blood at 1	BAFF-R Cells/100 CD19 Cells, Blood at 14	BAFF-R Cells/100 CD19 Cells, Blood at 42		BAFF-R Cells/100 CD19 Cells, Blood at 84
Physical Exam	Physical Exam at 8						Physical Exam at 14	Physical Exam at Unknown
Archived Sample, Saliva		Archived Sample, Saliva at 1	Archived Sample, Saliva at 14	Archived Sample, Saliva at 42		Archived Sample, Saliva at 84
Coagulation Panel (PT/INR, aPTT), Platelet poor plasma	Coagulation Panel (PT/INR, aPTT), Platelet poor plasma at 8	Coagulation Panel (PT/INR, aPTT), Platelet poor plasma at 1	Coagulation Panel (PT/INR, aPTT), Platelet poor plasma at 14	Coagulation Panel (PT/INR, aPTT), Platelet poor plasma at 42	Coagulation Panel (PT/INR, aPTT), Platelet poor plasma at 63	Coagulation Panel (PT/INR, aPTT), Platelet poor plasma at 84	Coagulation Panel (PT/INR, aPTT), Platelet poor plasma at 14	Coagulation Panel (PT/INR, aPTT), Platelet poor plasma at Unknown
PK Sampling, Plasma			PK Sampling, Plasma at 14	PK Sampling, Plasma at 42		PK Sampling, Plasma at 84
Troponin I Cardiac [Mass/Vol], Serum or Plasma	Troponin I Cardiac [Mass/Vol], Serum or Plasma at 8	Troponin I Cardiac [Mass/Vol], Serum or Plasma at 1	Troponin I Cardiac [Mass/Vol], Serum or Plasma at 14	Troponin I Cardiac [Mass/Vol], Serum or Plasma at 42	Troponin I Cardiac [Mass/Vol], Serum or Plasma at 63	Troponin I Cardiac [Mass/Vol], Serum or Plasma at 84	Troponin I Cardiac [Mass/Vol], Serum or Plasma at 14	Troponin I Cardiac [Mass/Vol], Serum or Plasma at Unknown
Lipid Panel (CHEM), Serum or Plasma	Lipid Panel (CHEM), Serum or Plasma at 8	Lipid Panel (CHEM), Serum or Plasma at 1	Lipid Panel (CHEM), Serum or Plasma at 14	Lipid Panel (CHEM), Serum or Plasma at 42	Lipid Panel (CHEM), Serum or Plasma at 63	Lipid Panel (CHEM), Serum or Plasma at 84	Lipid Panel (CHEM), Serum or Plasma at 14	Lipid Panel (CHEM), Serum or Plasma at Unknown
Cathepsin S [Mass/Vol], Serum or Plasma		Cathepsin S [Mass/Vol], Serum or Plasma at 1	Cathepsin S [Mass/Vol], Serum or Plasma at 14	Cathepsin S [Mass/Vol], Serum or Plasma at 42		Cathepsin S [Mass/Vol], Serum or Plasma at 84
Urinalysis Macro Panel by Dipstick, Urine	Urinalysis Macro Panel by Dipstick, Urine at 8	Urinalysis Macro Panel by Dipstick, Urine at 1	Urinalysis Macro Panel by Dipstick, Urine at 14	Urinalysis Macro Panel by Dipstick, Urine at 42	Urinalysis Macro Panel by Dipstick, Urine at 63	Urinalysis Macro Panel by Dipstick, Urine at 84	Urinalysis Macro Panel by Dipstick, Urine at 14	Urinalysis Macro Panel by Dipstick, Urine at Unknown
Beta-2-Microglobulin [Mass/Vol], Plasma		Beta-2-Microglobulin [Mass/Vol], Plasma at 1	Beta-2-Microglobulin [Mass/Vol], Plasma at 14	Beta-2-Microglobulin [Mass/Vol], Plasma at 42		Beta-2-Microglobulin [Mass/Vol], Plasma at 84
HBV and HCV Screening and Diagnosis, Serum	HBV and HCV Screening and Diagnosis, Serum at 8
DNA, Blood		DNA, Blood at 1
Archived Sample, Tear		Archived Sample, Tear at 1	Archived Sample, Tear at 14	Archived Sample, Tear at 42		Archived Sample, Tear at 84
Biopsy, Salivary Gland		Biopsy, Salivary Gland at 1				Biopsy, Salivary Gland at 84
Phosphate [Mass/Vol], Serum or Plasma	Phosphate [Mass/Vol], Serum or Plasma at 8	Phosphate [Mass/Vol], Serum or Plasma at 1	Phosphate [Mass/Vol], Serum or Plasma at 14	Phosphate [Mass/Vol], Serum or Plasma at 42	Phosphate [Mass/Vol], Serum or Plasma at 63	Phosphate [Mass/Vol], Serum or Plasma at 84	Phosphate [Mass/Vol], Serum or Plasma at 14	Phosphate [Mass/Vol], Serum or Plasma at Unknown
Chemistry Panel (CHEM-14), Serum or Plasma	Chemistry Panel (CHEM-14), Serum or Plasma at 8	Chemistry Panel (CHEM-14), Serum or Plasma at 1	Chemistry Panel (CHEM-14), Serum or Plasma at 14	Chemistry Panel (CHEM-14), Serum or Plasma at 42	Chemistry Panel (CHEM-14), Serum or Plasma at 63	Chemistry Panel (CHEM-14), Serum or Plasma at 84	Chemistry Panel (CHEM-14), Serum or Plasma at 14	Chemistry Panel (CHEM-14), Serum or Plasma at Unknown
Gamma Glutamyl Transferase [Act/Vol], Serum or Plasma	Gamma Glutamyl Transferase [Act/Vol], Serum or Plasma at 8	Gamma Glutamyl Transferase [Act/Vol], Serum or Plasma at 1	Gamma Glutamyl Transferase [Act/Vol], Serum or Plasma at 14	Gamma Glutamyl Transferase [Act/Vol], Serum or Plasma at 42	Gamma Glutamyl Transferase [Act/Vol], Serum or Plasma at 63	Gamma Glutamyl Transferase [Act/Vol], Serum or Plasma at 84	Gamma Glutamyl Transferase [Act/Vol], Serum or Plasma at 14	Gamma Glutamyl Transferase [Act/Vol], Serum or Plasma at Unknown
IgM [Mass/Vol], Serum	IgM [Mass/Vol], Serum at 8	IgM [Mass/Vol], Serum at 1		IgM [Mass/Vol], Serum at 42		IgM [Mass/Vol], Serum at 84	IgM [Mass/Vol], Serum at 14	IgM [Mass/Vol], Serum at Unknown
Lymphocyte T-Cell, B-Cell and NK Subsets Panel, Blood		Lymphocyte T-Cell, B-Cell and NK Subsets Panel, Blood at 1	Lymphocyte T-Cell, B-Cell and NK Subsets Panel, Blood at 14	Lymphocyte T-Cell, B-Cell and NK Subsets Panel, Blood at 42		Lymphocyte T-Cell, B-Cell and NK Subsets Panel, Blood at 84
Demographics	Demographics at 8
Informed Consent Obtained	Informed Consent Obtained at 8
Schirmer Test		Schirmer Test at 1	Schirmer Test at 14	Schirmer Test at 42		Schirmer Test at 84

◆ marks the fixed reference the other visits are timed from. Study days are not shown: the timings in this schedule do not connect every visit to it.

No entry point is declared, which USDM requires. The first visit is inferred as the only one nothing else leads to.

Conformance CDISC CORE CDISC Open Rules Engine 22 rules reported issues 207 rules 132 passed 17 with errors 4 with warnings 1 unrated 53 not evaluated 576 issues, most against Activity, Estimand and Location Engine 0.15.0 USDM v4.0 rules Run 16 Jun 2026

CDISC CORE

CDISC Open Rules Engine

22 rules reported issues 207 rules 132 passed 17 with errors 4 with warnings 1 unrated 53 not evaluated 576 issues, most against Activity, Estimand and Location Engine 0.15.0 USDM v4.0 rules Run 16 Jun 2026

JSON report Excel report

Partially executable: CDISC notes this rule may report issues that are not present. Engine wording: “partially executable - possible overreporting”.

In this document

Object	Location in the file	Values
Code Code_501	/study/versions/0/studyDesigns/0/objectives/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98772 decode Primary Objective
Code Code_601	/study/versions/0/studyDesigns/0/objectives/0/endpoints/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98772 decode Primary Endpoint
Code Code_502	/study/versions/0/studyDesigns/0/objectives/1/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Objective
Code Code_601	/study/versions/0/studyDesigns/0/objectives/1/endpoints/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Endpoint
Code Code_602	/study/versions/0/studyDesigns/0/objectives/1/endpoints/1/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Endpoint
Code Code_603	/study/versions/0/studyDesigns/0/objectives/1/endpoints/2/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Endpoint
Code Code_503	/study/versions/0/studyDesigns/0/objectives/2/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Objective
Code Code_601	/study/versions/0/studyDesigns/0/objectives/2/endpoints/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Endpoint
Code Code_504	/study/versions/0/studyDesigns/0/objectives/3/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Objective
Code Code_601	/study/versions/0/studyDesigns/0/objectives/3/endpoints/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Endpoint
Code Code_602	/study/versions/0/studyDesigns/0/objectives/3/endpoints/1/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Endpoint
Code Code_603	/study/versions/0/studyDesigns/0/objectives/3/endpoints/2/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Endpoint
Code Code_604	/study/versions/0/studyDesigns/0/objectives/3/endpoints/3/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98781 decode Secondary Endpoint
Code Code_505	/study/versions/0/studyDesigns/0/objectives/4/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Objective
Code Code_601	/study/versions/0/studyDesigns/0/objectives/4/endpoints/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Endpoint
Code Code_506	/study/versions/0/studyDesigns/0/objectives/5/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Objective
Code Code_601	/study/versions/0/studyDesigns/0/objectives/5/endpoints/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Endpoint
Code Code_507	/study/versions/0/studyDesigns/0/objectives/6/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Objective
Code Code_601	/study/versions/0/studyDesigns/0/objectives/6/endpoints/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Endpoint
Code Code_508	/study/versions/0/studyDesigns/0/objectives/7/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Objective
Code Code_601	/study/versions/0/studyDesigns/0/objectives/7/endpoints/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Endpoint
Code Code_509	/study/versions/0/studyDesigns/0/objectives/8/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Objective
Code Code_601	/study/versions/0/studyDesigns/0/objectives/8/endpoints/0/level	codeSystem http://www.cdisc.org codeSystemVersion 2025-09-26 code C98783 decode Exploratory Endpoint

Not evaluated 53

48 skipped · 5 engine errors 53 rules

DDF00084 Engine error There is not exactly one objective with a level of 'Primary Objective' within the study design. Failed to execute rule operation. Operation: distinct, Target: text, Domain: Objective, Error: 'Column not found: text'
DDF00107 Engine error The scheduled activity instance has a sub-timeline that is not defined within the same study design. Failed to execute rule operation. Operation: distinct, Target: parent_id, Domain: ScheduleTimeline, Error: 'timelineId'
DDF00114 Engine error The specified context of the condition is not a valid instance of either the Activity or ScheduledActivityInstance class (the value of the condition's contextIds attribute either matches the id of an instance that is not an Activity or ScheduledActivityInstance, or it does not match the id of any class instance). Failed to execute rule operation. Operation: record_count, Target: None, Domain: Condition, Error: Failed to execute rule operation. Domain Condition does not exist. Operation: record_count, Target: None, Core ID: CORE-000878
DDF00181 Engine error The study definition document version has more than one governance date with the same type and geographic scope. Cannot perform 'rand_' with a dtyped [float64] array and scalar of type [bool]
DDF00247 Engine error The text attribute contains non-conformant XHTML. Failed to execute rule operation. Operation: get_xhtml_errors, Target: text, Domain: Objective, Error: 'text'
DDF00006 Skipped One or more of the window attributes (windowLabel, windowLower, windowUpper) is missing.
DDF00013 Skipped A required biomedical concept property (isRequired=true) is not enabled (isEnabled is not true), or a disabled biomedical concept property (isEnabled=false) is required (isRequired is not false).
DDF00014 Skipped The biomedical concept category does not have any members or children.
DDF00020 Skipped Population of otherReason is not consistent with code - code.code is C17649 ('Other') but otherReason is blank, or otherReason is present but code.code is not C17649 ('Other').
DDF00024 Skipped The epoch references a previous or next epoch that is not specified within the same study design.
DDF00025 Skipped One or more of the window attributes (windowLabel, windowLower, windowUpper) contains a value for a Fixed Reference timing (type.code=C201358).
DDF00026 Skipped The scheduled activity instance is referencing its parent timeline as its sub-timeline.
DDF00028 Skipped The activity references a previous or next activity that is not specified within the same study design.
DDF00029 Skipped The encounter references a previous or next encounter that is not specified within the same study design.
DDF00034 Skipped The duration will vary (durationWillVary is not 'false' or reasonDurationWillVary is populated), but it is not fully defined (durationWillVary is not 'true' or reasonDurationWillVary is missing).
DDF00038 Skipped The scheduled decision instance does not refer to a default condition.
DDF00040 Skipped The study element is not referenced by any study cell.
DDF00044 Skipped The condition assignment's target is the same as its parent.
DDF00047 Skipped The study element is referenced by a study cell but was not defined within the same study design as the study cell: the parent_id of the study element ($parent_of_study_element) is not the same as parent_id of the study cell (parent_id.StudyCell).
DDF00061 Skipped The lower limit of the timing window (windowLower) is not a non-negative duration in ISO 8601 format.
DDF00062 Skipped The upper limit of the timing window (windowUpper) is not a non-negative duration in ISO 8601 format.
DDF00071 Skipped The study cell references an arm that is not defined within the same study design as the study cell.
DDF00072 Skipped The study cell references an epoch that is not defined within the same study design as the study cell.
DDF00090 Skipped The biomedical concept category is referenced more than once from the same activity.
DDF00102 Skipped The scheduled activity instance references a timeline exit that is not defined within the same schedule timeline as the scheduled activity instance.
DDF00112 Skipped The study intervention's role is not specified using the study intervention role (C207417) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive), and/or neither code nor decode is found in the codelist.
DDF00128 Skipped The study intervention's type is not specified using the Intervention Type Response (C99078) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive), and/or neither code nor decode is found in the codelist.
DDF00137 Skipped The reference is not a fixed value (it contains "usdm:ref") but it is not specified in the correct format.
DDF00143 Skipped The study amendment reason is not coded using the study amendment reason (C207415) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00152 Skipped The activity references a timeline that is not specified within the same study design.
DDF00175 Skipped The administration's frequency is not specified according to the extensible Frequency (C71113) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00176 Skipped The administration's route is not specified according to the extensible Route of Administration Response (C66729) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00179 Skipped The administrable dose form is not specified according to the extensible Pharmaceutical Dosage Form (C66726) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00180 Skipped The administrable product property type is not specified according to the extensible administrable product property type (C215479) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00183 Skipped The reference identifier type is not specified according to the extensible reference identifier type (C215478) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00187 Skipped The narrative content item text contains non-conformant XHTML.
DDF00199 Skipped The study impact type is not specified according to the extensible study amendment impact type (C215481) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00207 Skipped The medical device identifier type is not specified according to the extensible medical device identifier type (C215484) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00208 Skipped The administrable product sourcing is not specified according to the extensible administrable product sourcing (C215483) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00209 Skipped The medical device sourcing is not specified according to the extensible medical device sourcing (C215482) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00210 Skipped The administrable product's product designation is not specified using the product designation (C207418) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive), and/or neither code nor decode is found in the codelist.
DDF00214 Skipped The interventional study design's intent type is not specified according to the extensible Trial Intent Type Response (C66736) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00215 Skipped The interventional study design's sub type is not specified according to the extensible Trial Type Response (C66739) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00216 Skipped The study design's intervention model is not specified according to the extensible Intervention Model Response (C99076) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00217 Skipped The study design's blinding schema is not specified according to the extensible Trial Blinding Schema Response (C66735) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00218 Skipped The study design's characteristic is not specified according to the extensible study design characteristics (C207416) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00223 Skipped The study design's observational model is not specified according to the extensible Observational Study Model (C127259) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00224 Skipped The observational study design's time perspective is not specified according to the extensible Observational Study Time Perspective (C127261) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00225 Skipped The observational study design's sampling method is not specified according to the extensible Observational Study Sampling Method (C127260) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00226 Skipped The observational study design's sub type is not specified according to the extensible observational study design subtype (C215486) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00229 Skipped The study design's study phase is not specified according to the extensible Trial Phase Response (C66737) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
DDF00230 Skipped The study design's study type is not specified using the Study Type Response (C99077) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive), and/or neither code nor decode is found in the codelist.
DDF00259 Skipped The study role code is not specified using to the extensible study role code (C215480) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).

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