PD of VAY736 in Patients With Primary Sjögren's Syndrome

Phase 2

Completed

Conditions: Primary Sjögren's Syndrome

Interventions: Drug: VAY736
Drug: Placebo

Registration Number: NCT02149420

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This study was designed to evaluate the safety, tolerability, pharmacokinetics and therapeutic efficacy of a single intravenous infusion of VAY7346 monoclonal antibody in pSS patients

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VAY736 3 mg/kg	VAY736	single dose iv of VAY736 at a dose of 3mg/kg
VAY736 10 mg/kg	VAY736	single dose iv of VAY736 at a dose of 10mg/kg
Placebo	Placebo	single dose iv of Placebo. At Week 24 patients were offered to receive open label VAY736 10 mg/kg.

Primary Outcome Measures

Name	Time	Method
Overall Incidence of Adverse Events	Baseline to Week 24	Number of subjects with Adverse Events during the double blind treatment period.
Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	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.

Secondary Outcome Measures

Name	Time	Method
Change in Short Form (36) Health Survey (SF-36)	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.
VAY736 Serum Concentration - AUCinf	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 infinity \[mass × time / volume\]. The concentration of VAY736 was measured in the serum.
VAY736 Serum Concentration - Tmax	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The time to reach the maximum concentration after drug administration \[time\]. The concentration of VAY736 was measured in the serum.
Change in Multidimensional Fatigue Inventory (MFI)	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.
VAY736 Serum Concentration - CL	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The systemic (or total body) clearance from serum following intravenous administration \[volume / time\]. The concentration of VAY736 was measured in the serum.
Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)	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.
Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	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).
Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)	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).
VAY736 Serum Concentration - Vz	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The volume of distribution during the terminal elimination phase following intravenous administration \[volume\]. The concentration of VAY736 was measured in the serum.
VAY736 Serum Concentration - AUClast	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.
VAY736 Serum Concentration - Cmax	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	The observed maximum serum concentration following drug administration \[mass / volume\]. The concentration of VAY736 was measured in the serum.
VAY736 Serum Concentration - T1/2	0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.	Apparent terminal half-life, determined as the ln2/lambda_z or 0.693/lambda_z. The concentration of VAY736 was measured in the serum.