Clinical trial NCT02962895: Safety and Efficacy of VAY736 in Patients With Primary Sjogren's Syndrome (pSS)
Official title: Study of Safety and Efficacy of Multiple VAY736 Doses in Patients With Moderate to Severe Primary Sjogren's Syndrome (pSS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Sjogren Syndrome
Keywords: Sjogren
VAY736
ianalumab
pSS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-11-15
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group trial which planned to enroll approximately 180 patients with moderate to severe primary Sjögren's syndrome. The study was divided into 4 study periods:

Period 1: 4-week Screening to assess patient eligibility.

Period 2: 24-week Blinded treatment period.

Period 3: An extended blinded treatment period of 28 weeks. After Week 24 assessments, patients in the ianalumab 300 mg arm were re-randomized in a 1:1 ratio to either continue on ianalumab 300 mg s.c. q4w or switch to matching placebo up to Week 52.

Period 4: Post-treatment safety follow-up period. Patients who prematurely discontinued the study treatment at any time point or completed the treatment as planned entered the safety follow-up period.
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to determine the dose-response relationship of VAY736 for key efficacy and safety parameters

Detailed description: This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group trial that was divided into 4 study periods.

Period 1: A screening period of 4 weeks to assess patient eligibility. Patients could be re-screened only once, and no study-related re-screening procedure could be performed prior to written re-consent by the patient.

Period 2: A blinded treatment period of 24 weeks. At baseline, eligible patients were randomized to one of three ianalumab dose arms (VAY736 5 mg, 50 mg or 300 mg s.c.) or a placebo arm (placebo s.c.). Blinded study drug was administered every four weeks (q4w) for a 24-week period.

Except for Japan, randomization was stratified by baseline ESSDAI score (\<10 or ≥10 based on weighted scores). Separate blocks of randomization numbers were generated for patients in Japan versus the other countries participating to ensure that Japanese patients were equally distributed across all treatment groups in the study.

The primary endpoint was assessed at the end of Period 2 (Week 24). Treatment assignment in Period 2 remained double-blinded until the end of Period 3.

Period 3: An extended blinded treatment period of 28 weeks. After Week 24 assessments, patients in the ianalumab 300 mg arm were re-randomized in a 1:1 ratio to either continue on ianalumab 300 mg s.c. q4w or switch to matching placebo up to Week 52. Patients who received placebo during Period 2 were switched to ianalumab 150 mg s.c q4w up to Week 52. Patients who received 5 mg and 50 mg s.c. in Period 2 proceeded directly to safety follow-up (Period 4). Treatment assignment in Period 3 remained double-blinded.

Period 4: A post-treatment safety follow-up period. Patients who prematurely discontinued the study treatment at any time point or completed the treatment as planned entered the safety follow-up period. The minimum required duration of follow-up in the study was 20 weeks from the last administration of the study treatment (mandatory follow-up). The maximum duration of the follow-up was 2 years from the last dose of the study treatment, and it was defined by the level of recovery of CD19+ B-cells: conditional follow up (with reduced visit frequency) until CD19+ B-cell levels return to at least 80% of baseline or 50 cells/µL, whichever occurred first. Patients who had not yet recovered their B-cell counts two years after last ianalumab dosing were discharged from the study and had undergone their End of Study (EoS) visit. Patients who were treated with another immunomodulatory or immunosuppressive treatment (e.g., azathioprine, cyclophosphamide, high dose glucocorticosteroids) after completion of the minimum 20-week safety follow-up period were excluded from further safety follow-up.

Eligibility criteria: Inclusion Criteria:

* Fulfilled revised American European Consensus Group criteria for pSS
* Seropositive at screening for anti-Ro/SSA antibodies
* Screening ESSDAI value \>=6 scored from 7 domains: articular, cutaneous, glandular, lymphoadenopathy, constitutional, biologic and hematologic.

Exclusion Criteria:

* Secondary Sjogren's syndrome
* Use of other investigational drugs
* Active viral, bacterial or other infections
* Positive hepatitis B, hepatitis C, HIV or tuberculosis test results at screening

Primary outcomes:
measure: Least Squares Mean Change From Baseline in ESSDAI Score at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Least Squares Mean Change From Baseline in ESSDAI Score at Weeks 4, 8, 12, and 16
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Least Squares Mean Change From Baseline in ESSPRI Score at Week 24
timeFrame: Baseline, Week 24
measure: Least Squares Mean Change From Baseline in ESSPRI Score at Weeks 4, 8, 12 and 16
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16
measure: Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score Over 24 Weeks
timeFrame: Baseline, Week 24
measure: Least Squares Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) Score at Weeks 4, 8, 12 and 16
timeFrame: Baseline, Weeks 4, 8, 12 and 16
measure: Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) Over 24 Weeks
timeFrame: Baseline, Week 24
measure: Least Squares Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component (PCS) and Mental Component (MCS) at Weeks 4, 8, 12 and 16
timeFrame: Baseline, Weeks 4, 8, 12 and 16
measure: Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) Over 24 Weeks
timeFrame: Baseline, 24 weeks
measure: Least Squares Mean Change From Baseline in Physician's Global Assessment (PhGA) of Patient's Overall Disease Activity Using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16
timeFrame: Baseline, Weeks 4, 8, 12 and 16
measure: Patient's Global Assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24
timeFrame: Weeks 4, 8, 12, 16 and 24
measure: Least Squares Mean Change From Baseline in Salivary Flow Rate at Week 24
timeFrame: Baseline, 24 weeks
measure: Percent Change From Baseline in Whole Blood CD19+ B-cell Counts.
timeFrame: Baseline, Week 24, Week 28
measure: Kaplan-Meier Analysis for Time to Recovery to Baseline Like Values for B-cell Counts
timeFrame: Up to two years from last dose patient received.
measure: Peak Serum Concentration of VAY736
timeFrame: baseline to week 24, then week 28
Other outcomes:
Locations:
city: Plantation
country: United States
facility: Integral Rheumatology and Immunology Specialists IRIS
state: Florida
city: Indianapolis
country: United States
facility: Indiana Univ School of Dentistry
state: Indiana
city: Baltimore
country: United States
facility: The John Hopkins Jerome L Greene Sjogren
state: Maryland
city: Boston
country: United States
facility: Tufts School of Dental Medicine
state: Massachusetts
city: Rochester
country: United States
facility: AAIR Research Center
state: New York
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Wexford
country: United States
facility: Advanced Rheumatology and Arthritis Wellness Center
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College Of Medicine
state: Texas
city: San Antonio
country: United States
facility: First Outpatient Research Unit
state: Texas
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Brest
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Udine
country: Italy
facility: Novartis Investigative Site
state: UD
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Sasebo-city
country: Japan
facility: Novartis Investigative Site
state: Nagasaki
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
state: Zuid Holland
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Almada
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Orenburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Vigo
country: Spain
facility: Novartis Investigative Site
state: Pontevedra
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz De Tenerife
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: Southend
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Bowman SJ, Fox R, Dorner T, Mariette X, Papas A, Grader-Beck T, Fisher BA, Barcelos F, De Vita S, Schulze-Koops H, Moots RJ, Junge G, Woznicki JN, Sopala MA, Luo WL, Hueber W. Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjogren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet. 2022 Jan 8;399(10320):161-171. doi: 10.1016/S0140-6736(21)02251-0. Epub 2021 Nov 30.