PD of VAY736 in Patients With Primary Sjögren's Syndrome

Novartis Pharmaceuticals27 enrolled

Overview

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

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

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Primary Sjögren's Syndrome

Interventions

VAY736DRUG

PlaceboDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (1)

Novartis Investigative Site

Berlin, Germany

Outcomes

Primary Outcomes

Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)

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.

Time frame: Baseline, week 12

Overall Incidence of Adverse Events

Number of subjects with Adverse Events during the double blind treatment period.

Time frame: Baseline to Week 24

Secondary Outcomes

Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)

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.

Time frame: Baseline, week 12

Change in Short Form (36) Health Survey (SF-36)

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.

Time frame: Baseline, week 12

Change in Multidimensional Fatigue Inventory (MFI)

Data from ClinicalTrials.gov

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