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

NCT03905525 | Completed Phase 2 Results DMC FDA Drug

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

Brief Summary

This study was to evaluate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple doses of CFZ533 (iscalimab) in patients with Sjögren's Syndrome (SjS).

Conditions

Sjögren Syndrome

Keywords

Sjögren Syndrome (SjS); sicca syndrome; dryness; fatigue; autoimmune disease; European League Against Rheumatism (EULAR); EULAR Sjögren syndrome disease activity index (ESSDAI); EULAR Sjögren syndrome patient reported index (ESSPRI); monoclonal antibody; anti-CD40; iscalimab (CFZ533); TWINSS

Outcome Measures

Primary Outcomes (2)

• Cohort 1: Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) Score From Baseline at 24 Weeks as Compared to Placebo

  ESSDAI is a validated disease outcome measure for SjS that contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The domains (weights) are as follows: constitutional (3), lymphadenopathy (4), glandular (2), articular (2), cutaneous (3), pulmonary (5), renal (5), muscular (6), peripheral nervous system (PNS) (5), central nervous system (CNS) (5), hematological (2) and biological (1). The total score may vary between 0-123. It is considered low activity an ESSDAI \< 5; moderate activity 5-13, and high activity if ESSDAI is \>= 14.

  Baseline, Week 24

• Cohort 2: Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) Score From Baseline at 24 Weeks as Compared to Placebo.

  The ESSPRI is a self-evaluation index for measuring symptoms including pain, fatigue and dryness. Each symptom was measured with a single 0 (no symptoms) to 10 (severe symptoms) numerical scale and the final ESSPRI score is calculated by averaging these domains with a maximum severity score of 10.

  Baseline, Week 24

Secondary Outcomes (19)

• Cohort 1: Change From Baseline in ESSPRI at Week 24

  Baseline, Week 24

• Cohort 1: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24

  Baseline, 24 weeks

• Cohort 1: Change From Baseline in Physician Global Assessment (PhGA) at Week 24

  Baseline, 24 weeks

• Cohort 2: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24

  Baseline, 24 weeks

• Cohort 2: Change From Baseline in Physician Global Assessment (PhGA) at Week 24

  Baseline, 24 weeks

Study Arms (8)

Cohort 1 / Arm A

EXPERIMENTAL

3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Weeks 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

Drug: CFZ533

Cohort 1 / Arm B

EXPERIMENTAL

3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 300 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 300 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

Drug: CFZ533

Cohort 1 / Arm C

EXPERIMENTAL

3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 150 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 150 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

Drug: CFZ533

Cohort 1 / Arm D (Period 1)

PLACEBO COMPARATOR

Placebo treatment is administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.

Other: Placebo

Cohort 1 / Arm D1 (Period 2)

EXPERIMENTAL

Period 2: 3 weekly subcutaneous (s.c.) loading doses of 600 mg iscalimab on Week 24, 25 and 26. After Week 26 and up to Week 46 (last dose), iscalimab was administered bi-weekly at 600 mg.

Drug: CFZ533

Cohort 2 / Arm E

EXPERIMENTAL

3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

Drug: CFZ533

Cohort 2 / Arm F (Period 1)

PLACEBO COMPARATOR

Placebo treatment was administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.

Other: Placebo

Cohort 2 / Arm F1 (Period 2)

EXPERIMENTAL

Period 2: 3 weekly subcutaneous (s.c.) loading doses of iscalimab: 600 mg on Week 24, and 300 mg on Week 25 and Week 26. After Week 26, iscalimab was administered s.c. bi-weekly at 300 mg.

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 (Period 2); Cohort 2 / Arm E; Cohort 2 / Arm F1 (Period 2)

Placebo OTHER

liquid placebo for injections

Cohort 1 / Arm D (Period 1); Cohort 2 / Arm F (Period 1)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Both cohorts must have met all the following criteria:
• Signed informed consent must be obtained prior to participation in the study
• Male or female patient \>= 18 years of age
• Classification of Sjögren's Syndrome according to ACR/EULAR 2016 criteria (Shiboski et al 2016)
• Seropositive for anti-Ro/SSA antibodies
• Stimulated whole salivary flow rate of \>= 0.1 mL/min
• Able to communicate well with the Investigator to understand and comply with the requirements of the study
• Screening ESSDAI value \>= 5 within the following 8 organ domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematologic and biologic
• Patients with involvement of one or more of the remaining 4 domains are eligible but scores of these domains will not contribute to the assessment for eligibility for Cohort 1
• At selected sites participating in Cohort 2, patients who based on the above criterion 7, do not qualify for Cohort 1, should be further evaluated for Cohort 2
• Screening ESSPRI score of \>= 5
• Screening ESSPRI fatigue subscore \>= 5 or ESSPRI dryness subscore \>= 5
• Hypergammaglobulinemia defined by IgG greater than upper limit of normal (ULN) or lymphocytopenia (less than lower limit of normal (LLN)) or hypocomplementemia (low C3, or low C4 - when considered due to disease activity and not due to genetic factors)
• Score of \>= 30 on IDEEL symptom bother questionnaire at Screening

You may not qualify if:

• Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principal illness
• Use of other investigational drugs within 5 half-lives of enrollment or within 30 days whichever is longer, or longer if required by local regulations
• Prior treatment with any of the following within 6 months prior to randomization:
• B-cell depletors (e.g. rituximab, ianalumab) unless CD19+ B cell count have returned to ≥ 50 cells/µL
• abatacept
• anti-tumor necrosis factor alpha monoclonal anti-body
• intravenous/subcutaneous Ig; plasmapheresis; i.v. or oral cyclophosphamide
• i.v. or oral cyclosporine A
• any other immunosuppressants unless explicitly allowed in criterion #5
• Use of steroids (predniso(lo)ne or equivalent corticosteroid) at dose \> 10 mg/day
• Use of steroids and synthetic DMARDS at inconsistent dose and within 3 months prior to randomization

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (71)

North GA Rheumatology Group PC

Suwanee, Georgia, 30024, United States

Location

Indiana Univ School of Dentistry

Indianapolis, Indiana, 46202, United States

Location

Ochsner Health System

Baton Rouge, Louisiana, 70809, United States

Location

The John Hopkins Jerome L Greene Sjogren

Baltimore, Maryland, 21224, United States

Location

Tufts School of Dental Medicine

Boston, Massachusetts, 02111, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Uni Wisconsin School Med Pub Health

Madison, Wisconsin, 53792, United States

Location

Novartis Investigative Site

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, G9A 3Y2, Canada

Location

Novartis Investigative Site

Valdivia, Los Ríos Region, 5110683, Chile

Location

Novartis Investigative Site

Santiago, RM, 7500588, Chile

Location

Novartis Investigative Site

Santiago, Santiago Metropolitan, 7500571, Chile

Location

Novartis Investigative Site

Santiago, Santiago Metropolitan, 7500710, Chile

Location

Novartis Investigative Site

Concepción, 6740, 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, 59037, France

Location

Novartis Investigative Site

Paris, 75014, France

Location

Novartis Investigative Site

Strasbourg, 67000, France

Location

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Novartis Investigative Site

Würzburg, Bavaria, 97080, Germany

Location

Novartis Investigative Site

Dresden, Saxony, 01307, Germany

Location

Novartis Investigative Site

Bonn, 53105, 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, 3104802, Israel

Location

Novartis Investigative Site

Kfar Saba, 4428164, Israel

Location

Novartis Investigative Site

Ramat Gan, 5265601, Israel

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Pisa, PI, 56126, 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, 857-1195, Japan

Location

Novartis Investigative Site

Kurashiki, Okayama-ken, 710-0824, 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

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

Almada, 2805-267, 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, Yenimahalle, 06500, 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; Autoimmune Diseases

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; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

1 862 778 8300

Study Officials

• Study Director Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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, were blinded 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 were screened and enrolled into one of the 2 study Cohorts: Cohort 1: At baseline subjects were 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 were 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 continued 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: May 18, 2026
• Results First Posted: May 18, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

NL (2); CA (3); CL (5); BR (3); 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); JP (5)