PD of VAY736 in Patients With Primary Sjögren's Syndrome (CVAY736X2201)

Novartis

Status and phase: Completed; Phase 2

Conditions: Primary Sjögren's Syndrome

Treatments: Drug: Placebo; Drug: VAY736

Study type: Interventional

Funder types: Industry

Identifiers

NCT02149420

2013-000250-22 (EudraCT Number)

CVAY736X2201

Details and patient eligibility

About

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

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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27 participants in 3 patient groups, including a placebo group

VAY736 3 mg/kg

Experimental group

Description:

single dose iv of VAY736 at a dose of 3mg/kg

Treatment:

Drug: VAY736

VAY736 10 mg/kg

Experimental group

Description:

single dose iv of VAY736 at a dose of 10mg/kg

Treatment:

Drug: VAY736

Placebo

Placebo Comparator group

Description:

single dose iv of Placebo. At Week 24 patients were offered to receive open label VAY736 10 mg/kg.

Treatment:

Drug: Placebo