PD of VAY736 in Patients With Primary Sjögren's Syndrome

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

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.

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