Study of Safety and Efficacy of Multiple Doses of CFZ533 in Two Distinct Populations of Patients With Sjogren's Syndrome

NCT03905525 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: CCFZ533B22012018-004476-35
• Study Type: interventional
• Target: 273
• Locations: 22 countries
• Sites: 69

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.

Conditions

Sjögren Syndrome

Keywords

Sjögren; fatigue; dryness; anti-CD40; CFZ533; iscalimab; TWINSS; autoimmune

Outcome Measures

Primary Outcomes (2)

• Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo

  Cohort 1 - Efficacy

  24 weeks

• Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score from baseline at 24 weeks as compared to placebo.

  Cohort 2 - Efficacy

  24 weeks

Secondary Outcomes (9)

• Change from baseline in ESSPRI at Week 24

  24 weeks

• Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24

  24 weeks

• Change from baseline in Physician Global Assessment (PhGA) at Week 24

  24 weeks

• Change from baseline in ESSDAI at Week 24

  24 weeks

• 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.

  24 weeks

Study Arms (8)

Cohort 1 /Arm A

EXPERIMENTAL

CFZ533 dose 1

Drug: CFZ533

Cohort 1/Arm B

EXPERIMENTAL

CFZ533 dose 2

Drug: CFZ533

Cohort 1/Arm C

EXPERIMENTAL

CFZ533 dose 3

Drug: CFZ533

Cohort 1/Arm D

PLACEBO COMPARATOR

Placebo dose (up to week 24)

Other: Placebo

Cohort 1/Arm D1

EXPERIMENTAL

CFZ533 dose 1 (from week 24)

Drug: CFZ533

Cohort 2/Arm E

EXPERIMENTAL

CFZ533 dose 1

Drug: CFZ533

Cohort 2/Arm F

PLACEBO COMPARATOR

Placebo dose (up to week 24)

Other: Placebo

Cohort 2/Arm F1

EXPERIMENTAL

CFZ533 dose 2 (from week 24)

Drug: CFZ533

Interventions

CFZ533 DRUG

Biological

Also known as: iscalimab

Cohort 1 /Arm A; Cohort 1/Arm B; Cohort 1/Arm C; Cohort 1/Arm D1; Cohort 2/Arm E; Cohort 2/Arm F1

Placebo OTHER

liquid placebo for injections

Cohort 1/Arm D; Cohort 2/Arm F

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ESSDAI ≥ 5 within the 8 predefined organ domains
• ESSPRI score of ≥5
• ESSPRI fatigue subscore ≥ 5 or ESSPRI dryness subscore ≥ 5

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (71)

Novartis Investigative Site

Duluth, Georgia, 30096, United States

Location

Novartis Investigative Site

Indianapolis, Indiana, 46202, United States

Location

Novartis Investigative Site

Baton Rouge, Louisiana, 70809, United States

Location

Novartis Investigative Site

Baltimore, Maryland, 21224, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02111, United States

Location

Novartis Investigative Site

Mineola, New York, 11501, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19104, United States

Location

Novartis Investigative Site

Madison, Wisconsin, 53792, United States

Location

Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, C1055AAF, Argentina

Location

Novartis Investigative Site

CABA, 1426, Argentina

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Graz, 8036, Austria

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Vitória, Espírito Santo, 29055 450, Brazil

Location

Novartis Investigative Site

Juiz de Fora, Minas Gerais, 36010 570, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01244-030, Brazil

Location

Novartis Investigative Site

Toronto, Ontario, M5T 2S8, Canada

Location

Novartis Investigative Site

Rimouski, Quebec, G5L 5T1, Canada

Location

Novartis Investigative Site

Trois-Rivières, Quebec, G8Z 1Y2, Canada

Location

Novartis Investigative Site

Valdivia, Los Ríos Region, 5110683, Chile

Location

Novartis Investigative Site

Santiago, RM, 7500588, Chile

Location

Novartis Investigative Site

Concepción, 6740, Chile

Location

Novartis Investigative Site

Santiago, 7500571, Chile

Location

Novartis Investigative Site

Santiago, 7500710, Chile

Location

Novartis Investigative Site

Medellín, Antioquia, 050001, Colombia

Location

Novartis Investigative Site

Barranquilla, Atlántico, 080002, Colombia

Location

Novartis Investigative Site

Cali, Valle del Cauca Department, 760012, Colombia

Location

Novartis Investigative Site

Brest, 29200, France

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

Location

Novartis Investigative Site

Lille, 59000, France

Location

Novartis Investigative Site

Paris, 75014, France

Location

Novartis Investigative Site

Strasbourg, 67000, France

Location

Novartis Investigative Site

Bonn, 53105, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Athens, 115 27, Greece

Location

Novartis Investigative Site

Székesfehérvár, Fejér, 8000, Hungary

Location

Novartis Investigative Site

Budapest, 1023, Hungary

Location

Novartis Investigative Site

Szeged, 6720, Hungary

Location

Novartis Investigative Site

Haifa, 3339419, Israel

Location

Novartis Investigative Site

Kfar Saba, 44281, Israel

Location

Novartis Investigative Site

Ramat Gan, 52621, Israel

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Pisa, PI, 56124, Italy

Location

Novartis Investigative Site

Udine, UD, 33100, Italy

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 457 8510, Japan

Location

Novartis Investigative Site

Sasebo, Nagasaki, 857-1165, Japan

Location

Novartis Investigative Site

Kurashiki, Okayama-ken, 710-8522, Japan

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104-8560, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 160 8582, Japan

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

Location

Novartis Investigative Site

Almada, 2801 951, Portugal

Location

Novartis Investigative Site

Lisbon, 1050-034, Portugal

Location

Novartis Investigative Site

Lisbon, 1649-035, Portugal

Location

Novartis Investigative Site

Ponte de Lima, 4990 041, Portugal

Location

Novartis Investigative Site

Brasov, 500283, Romania

Location

Novartis Investigative Site

Cluj-Napoca, 400006, Romania

Location

Novartis Investigative Site

Kazan', 420097, Russia

Location

Novartis Investigative Site

Moscow, 115522, Russia

Location

Novartis Investigative Site

Orenburg, 460000, Russia

Location

Novartis Investigative Site

Saint Petersburg, 195257, Russia

Location

Novartis Investigative Site

Tomsk, 634009, Russia

Location

Novartis Investigative Site

Yekaterinburg, 620028, Russia

Location

Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

Location

Novartis Investigative Site

Stockholm, SE, 113 65, Sweden

Location

Novartis Investigative Site

Ankara, 06560, Turkey (Türkiye)

Location

Novartis Investigative Site

Birmingham, B15 2TH, United Kingdom

Location

Novartis Investigative Site

Doncaster, DN2 5LT, United Kingdom

Location

Novartis Investigative Site

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• Fisher BA, Mariette X, Papas A, Grader-Beck T, Bootsma H, Ng WF, van Daele PLA, Finzel S, Noaiseh G, Elgueta S, Hermann J, McCoy SS, Akpek E, Bookman A, Sopala M, Montecchi-Palmer M, Luo WL, Scheurer C, Hueber W; TWINSS study group. Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sjogren's disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study. Lancet. 2024 Aug 10;404(10452):540-553. doi: 10.1016/S0140-6736(24)01211-X. Epub 2024 Jul 31.

  PMID: 39096929 DERIVED

MeSH Terms

Conditions

Sjogren's Syndrome; Fatigue

Interventions

iscalimab

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Study Director Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients, investigator staff, persons performing the assessments, will remain blind to the identity of the treatment within each cohort from the time of randomization until end of the study visit (week 60)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: April 5, 2019
• Study Start: October 1, 2019
• Primary Completion: September 28, 2022
• Study Completion: June 6, 2023
• Last Updated: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share

Locations

NL (2); CA (3); CL (5); BR (3); JP (5); FR (5); AU (1); IL (3); PT (4); KR (1); RU (6); CO (3); SE (1); GR (1); IT (3); RO (2); US (8); HU (3); DE (4); GB (3); TU (1); AR (2)