Clinical trial NCT04541589: Study of Safety and Tolerability of CFZ533 in Patients With Sjögren's Syndrome
Official title: A TWINSS Extension Trial to Evaluate the Safety and Tolerability of CFZ533 (Iscalimab) at Two Dose Levels Administered Subcutaneously in Patients With Sjögren's Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sjogren's Syndrome
Keywords: Sjogren's Syndrome
autoimmune
ESSDAI
ESSPRI
anti-CD40
CFZ533
iscalimab
TWINSS Extension
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-09-09
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Upon completion of the core study (NCT03905525), Investigators will use their clinical judgment including responder definitions to decide if it is beneficial for participants to continue with the Extension study based upon response to therapy at the end of the treatment period of the core study.

Participants will be re-assigned to one of the following two treatment arms:

* Arm 1 - Iscalimab Dose 1 s.c. Q2W
* Arm 2 - Iscalimab Dose 2 s.c. Q2W and Placebo

At Week 60 of the TWINSS core study (NCT03905525), all eligible participants from the core study can opt to be enrolled in the extension study
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and tolerability of iscalimab at two dose levels in patients with Sjögren's Syndrome, who participated in the TWINSS core study, CCFZ533B2201(NCT03905525). Additionally, this Extension study will further explore the pharmacokinetics (PK) and efficacy of iscalimab at two dose level.

Detailed description: This Extension study is a 48-week treatment study, with a safety follow-up period of 12 weeks. This study will evaluate the safety and tolerability of iscalimab at two dose levels in patients with Sjögren's Syndrome, who must have participated in the TWINSS core study, CCFZ533B2201 (NCT03905525) and must have completed the entire treatment period up to Week 48 and the follow-up period up to Week 60.

Study treatment will be administered as bi-weekly subcutaneous injections (Q2W s.c.) via prefilled syringes (PFS).

Eligibility criteria: Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

1. Participants must have participated in the TWINSS core study, CCFZ533B2201 (NCT03905525), and must have completed the entire treatment period up to Week 48 and the follow-up period up to Week 60
2. Signed informed consent must be obtained prior to participation in the Extension study (i.e. before commencement of the Week 60 assessments of the core study)
3. In the judgement of the Investigator, participants must be expected to clinically benefit from continued iscalimab therapy

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study.

1. Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principle illness, specifically:

   * Moderate-to-severe active systemic lupus erythematosus (SLE) with anti-dsDNA positivity and renal involvement, or other organ involvement that impedes on ability to score ESSDAI domains
   * Active rheumatoid arthritis (RA) that impedes on the ability to score the ESSDAI articular domain
   * Systemic sclerosis
   * Any other concurrent connective tissue disease (e.g., lupus nephritis (LN), large vessel vasculitis (LVV), Sharp syndrome (mixed connective tissue disease) that is active and requires immunosuppressive treatment outside the scope of this trial and would impede on Sjögren's Syndrome organ domain assessments
2. Use of other investigational drugs other than iscalimab during the core study
3. Active uncontrolled viral, bacterial or other infections requiring systemic treatment at the time of enrollment, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms
4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test
5. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 14 weeks after stopping of investigational drug.
6. Missing ESSDAI (Cohort 1 and Cohort 2) or ESSPRI (Cohort 2) scores in the core study at Weeks 0 and 4 or Weeks 40 and 48.

Primary outcomes:
measure: Incidence of Treatment-emergent adverse events (TEAEs)
timeFrame: 60 weeks
Secondary outcomes:
measure: Free iscalimab concentration in plasma during the treatment (Ctrough) and follow-up (up to end of study) periods
timeFrame: 60 weeks
measure: Incidence of anti-iscalimab antibodies in plasma at analysis visits up to end of study
timeFrame: 60 weeks
Other outcomes:
Locations:
city: Duluth
country: United States
facility: North GA Rheumatology Group PC CAIN457FUS01
state: Georgia
city: Baton Rouge
country: United States
facility: Ochsner Health System Research Department
state: Louisiana
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: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Philadelphia
country: United States
facility: Perelman School of Medicine
state: Pennsylvania
city: Madison
country: United States
facility: Uni Wisconsin School Med Pub Health .
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: Sao 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: 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: 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: 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: 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: 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: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
state: Zuid Holland
city: Groningen
country: Netherlands
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: 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: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: