Clinical trial NCT02149420: PD of VAY736 in Patients With Primary Sjögren's Syndrome
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Sjögren's Syndrome
Keywords: primary Sjögren's syndrome, pharmacodynamics
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-05-29
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)
timeFrame: Baseline, week 12
measure: Overall Incidence of Adverse Events
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)
timeFrame: Baseline, week 12
measure: Change in Short Form (36) Health Survey (SF-36)
timeFrame: Baseline, week 12
measure: Change in Multidimensional Fatigue Inventory (MFI)
timeFrame: Baseline, week 12
measure: Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)
timeFrame: Baseline, week 12
measure: Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)
timeFrame: Baseline, week 12
measure: VAY736 Serum Concentration - AUCinf
timeFrame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
measure: VAY736 Serum Concentration - AUClast
timeFrame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
measure: VAY736 Serum Concentration - CL
timeFrame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
measure: VAY736 Serum Concentration - Cmax
timeFrame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
measure: VAY736 Serum Concentration - T1/2
timeFrame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
measure: VAY736 Serum Concentration - Tmax
timeFrame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
measure: VAY736 Serum Concentration - Vz
timeFrame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: