Clinical trial NCT03905525: Study of Safety and Efficacy of Multiple Doses of CFZ533 in Two Distinct Populations of Patients With Sjogren's Syndrome
Official title: A 48-week, 6-arm, Randomized, Double-blind, Placebo-controlled Multicenter Trial to Assess the Safety and Efficacy of Multiple CFZ533 Doses Administered Subcutaneously in Two Distinct Populations of Patients With Sjogren's Syndrome (TWINSS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sjögren Syndrome
Keywords: Sjögren
fatigue
dryness
anti-CD40
CFZ533
iscalimab
TWINSS
autoimmune
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-04-05
Enrollment: 273
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be screened and enrolled into one of the 2 study Cohorts:

Cohort 1: At baseline subjects will be randomized in ratio 1:1:1:1 into one of three CFZ533 (iscalimab) arms (A, B or C) or to placebo (Arm D). After completion of 24 weeks of treatment (Period 1) placebo patients (Arm D) will be switched to active treatment (Arm D1) for the subsequent 24 weeks (Period 2).

Cohort 2: At baseline subjects will be randomized in ratio 1:1 to iscalimab (Arm E) or to placebo (Arm F). After completion of 24 weeks of treatment (Period 1), placebo patients (Arm F) will be switched to iscalimab active treatment (Arm F1) for the subsequent 24 weeks (Period 2).

All patients treated with iscalimab (Arms A,B,C,and E) in Period 1 will continue the same study treatment in Period 2.
Primary purpose: TREATMENT

Brief summary: This study will evaluate safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple doses of CFZ533 (iscalimab) in patients with Sjögren's Syndrome.

Detailed description: This is a double-blind, randomized, placebo-controlled, multicenter study of CFZ533 in 2 distinct populations (cohorts) of patients with Sjögren's Syndrome: 1) moderate-to-severe disease (systemic and symptomatic involvement) and; 2) low systemic involvement but high symptom burden.

The study includes up to 6 weeks screening period, 48 weeks of treatment (divided into treatment periods of 24 weeks each) and 12 weeks follow up. Study treatment will be administered as bi-weekly subcutaneous injections.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Male or female patient ≥ 18 years of age
* Classification of Sjögren's Syndrome according to ACR/EULAR 2016 criteria (Shiboski et al 2017)
* Seropositive for anti-Ro/SSA antibodies
* Stimulated whole salivary flow rate of ≥ 0.1 mL/min

Inclusion criteria specific for Cohort 1:

* ESSDAI ≥ 5 within the 8 predefined organ domains
* ESSPRI score of ≥5

Inclusion criteria specific for Cohort 2:

* ESSDAI \< 5 within 8 domains scored for inclusion criterion for Cohort 1
* ESSPRI fatigue subscore ≥ 5 or ESSPRI dryness subscore ≥ 5

Exclusion Criteria:

* Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principle illness
* Use of other investigational drugs
* Prior use of B cell depleting therapies, abatacept or any other immunosuppressants unless specifically allowed be the protocol.
* Use of steroids at dose \>10 mg/day.
* Uncontrolled ocular rosacea (affecting the eye adnexa), posterior blepharitis or Meibomian gland disease (this criterion applies only to patients considered for Cohort 2)
* Active viral, bacterial or other infections requiring systemic treatment
* Receipt of live/attenuated vaccine within a 2-month period prior to randomization.
* Chronic infection with hepatitis B (HBV) or hepatitis C (HCV).
* Evidence of active tuberculosis (TB) infection.

Primary outcomes:
measure: Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo
timeFrame: 24 weeks
measure: Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score from baseline at 24 weeks as compared to placebo.
timeFrame: 24 weeks
Secondary outcomes:
measure: Change from baseline in ESSPRI at Week 24
timeFrame: 24 weeks
measure: Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24
timeFrame: 24 weeks
measure: Change from baseline in Physician Global Assessment (PhGA) at Week 24
timeFrame: 24 weeks
measure: Change from baseline in ESSDAI at Week 24
timeFrame: 24 weeks
measure: Proportion of subjects with at least 12 points improvement measured by score of Impact of Dry Eye on Everyday Life (IDEEL) questionnaire symptom bother module at Week 24.
timeFrame: 24 weeks
measure: Incidence of adverse events (AEs), serious adverse events (SAEs) from baseline to Week 24 and from week 24 to the end of study
timeFrame: 60 weeks
measure: Serum Free Light Chain (FLC) levels at analysis visit up to end of study
timeFrame: 60 weeks
measure: Immunoglobulin IgG and IgM levels at analysis visits up to end of study
timeFrame: 60 weeks
measure: Percent change from baseline in plasma CXCL-13 levels at analysis visits up to end of study
timeFrame: 60 weeks
Other outcomes:
Locations:
city: Duluth
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Baton Rouge
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Mineola
country: United States
facility: Novartis Investigative Site
state: New York
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Madison
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Vitoria
country: Brazil
facility: Novartis Investigative Site
state: ES
city: Juiz de Fora
country: Brazil
facility: Novartis Investigative Site
state: MG
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Rimouski
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Trois Rivieres
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Valdivia
country: Chile
facility: Novartis Investigative Site
state: Los Rios
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: RM
city: Concepcion
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
state: Atlantico
city: Cali
country: Colombia
facility: Novartis Investigative Site
state: Valle Del Cauca
city: Brest
country: France
facility: Novartis Investigative Site
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Szekesfehervar
country: Hungary
facility: Novartis Investigative Site
state: Fejer
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
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: Kurashiki
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
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: Ponte de Lima
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: Kazan
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: Tomsk
country: Russian Federation
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
state: SE
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Doncaster
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Study Director Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: