- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02149420
PD of VAY736 in Patients With Primary Sjögren's Syndrome (CVAY736X2201)
A Single Dose, Double-blind, Placebo-controlled, Parallel Study to Assess the Pharmacodynamics, Pharmacokinetics and Safety and Tolerability of VAY736 in Patients With Primary Sjögren's Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients were enrolled in 2 sequential cohorts:
Cohort 1: 6 patients received 3 mg/kg or Placebo (2:1 ratio) Cohort 2: 21 patients received 10 mg/kg, 3 mg/kg or Placebo (6:1:3 ratio)
At week 24 the blind was broken to assess continuation in the trial:
- If a patient received VAY736 and their B cell recovery was demonstrated at Week 24, then patients completed the trial.
- If a patient received VAY736 and their B cell recovery was NOT demonstrated at Week 24, then patients were followed up until B cell recovery was demonstrated
- If a patient received placebo, they were offered the option of receiving open-label VAY736 (10 mg/kg) in a separate treatment arm.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Berlin, Germany, 10117
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA:
- Fulfilled revised European US consensus criteria for pSS
- ESSDAI value ≥ 6
- Elevated serum titers at screening of ANA (≥ 1:160)
- Seropositive at screening for anti-SSA and/or anti-SSB antibodies
- Stimulated whole salivary flow rate at screening of > 0 mL/min
EXCLUSION CRITERIA:
- Prior or previous use of (specific dosages and intervals prior to study start may apply): B-cell depleting therapy (e.g., rituximab), Prednisone, anti-BAFF mAb, CTLA4-Fc Ig (abatacept), anti-TNF-α mAb, cyclophosphamide, azathioprine and medications known to cause dry mouth.
Hydroxychloroquine or methotrexate in a consistent dose for ≥ 3 months prior to randomization is allowed
- Active or recent history of clinically significant infection
- Vaccination within 2 month prior to study
- History of primary or secondary immunodeficiency
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: VAY736 3 mg/kg
single dose iv of VAY736 at a dose of 3mg/kg
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Experimental: VAY736 10 mg/kg
single dose iv of VAY736 at a dose of 10mg/kg
|
|
Placebo Comparator: Placebo
single dose iv of Placebo.
At Week 24 patients were offered to receive open label VAY736 10 mg/kg.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)
Time Frame: Baseline, week 12
|
The effect of VAY736 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12.
The instrument contains 12 organ-specific domains contributing to disease activity.
For each domain, features of disease activity are scored in 3 or 4 levels according to their severity.
These scores are then summed across the 12 domains in a weighted manner to provide the total score (range 0-123).
A reduction from baseline indicates improvement in patients.
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Baseline, week 12
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Overall Incidence of Adverse Events
Time Frame: Baseline to Week 24
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Number of subjects with Adverse Events during the double blind treatment period.
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Baseline to Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)
Time Frame: Baseline, week 12
|
The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue and mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely severe).
The final ESSPRI score is the average of three: dryness, pain and fatigue.
A reduction from baseline indicates the improvement of symptoms.
During the study all individual scores were reported as 1 to 10 instead.
A linear transformation was reported to map the scores to the range of 0-10.
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Baseline, week 12
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Change in Short Form (36) Health Survey (SF-36)
Time Frame: Baseline, week 12
|
The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health.
The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100.
An increase from baseline in either component summary score indicates reduced disease burden.
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Baseline, week 12
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Change in Multidimensional Fatigue Inventory (MFI)
Time Frame: Baseline, week 12
|
The MFI is a patient self-reported outcome measure (questionnaires) to assess fatigue covering the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity.
Each dimension has a posible range from 4-20.
A reduction from baseline in MFI indicates improvement.
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Baseline, week 12
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Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)
Time Frame: Baseline, week 12
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The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).
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Baseline, week 12
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Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)
Time Frame: Baseline, week 12
|
The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).
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Baseline, week 12
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VAY736 Serum Concentration - AUCinf
Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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The area under the serum concentration-time curve from time zero to infinity [mass × time / volume].
The concentration of VAY736 was measured in the serum.
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0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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VAY736 Serum Concentration - AUClast
Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
|
The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration [mass × time / volume].
The concentration of VAY736 was measured in the serum.
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0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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VAY736 Serum Concentration - CL
Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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The systemic (or total body) clearance from serum following intravenous administration [volume / time].
The concentration of VAY736 was measured in the serum.
|
0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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VAY736 Serum Concentration - Cmax
Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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The observed maximum serum concentration following drug administration [mass / volume].
The concentration of VAY736 was measured in the serum.
|
0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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VAY736 Serum Concentration - T1/2
Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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Apparent terminal half-life, determined as the ln2/lambda_z or 0.693/lambda_z.
The concentration of VAY736 was measured in the serum.
|
0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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VAY736 Serum Concentration - Tmax
Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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The time to reach the maximum concentration after drug administration [time].
The concentration of VAY736 was measured in the serum.
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0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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VAY736 Serum Concentration - Vz
Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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The volume of distribution during the terminal elimination phase following intravenous administration [volume].
The concentration of VAY736 was measured in the serum.
|
0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Eye Diseases
- Disease
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Stomatognathic Diseases
- Mouth Diseases
- Lacrimal Apparatus Diseases
- Arthritis, Rheumatoid
- Xerostomia
- Salivary Gland Diseases
- Dry Eye Syndromes
- Syndrome
- Sjogren's Syndrome
Other Study ID Numbers
- CVAY736X2201
- 2013-000250-22 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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