Study of safety and efficacy of multiple doses of CFZ533 in two distinct populations of patients with Sjögren’s Syndrome

• Register: EUCTR
• Last refreshed on: 2 May 2022
• Main ID: EUCTR2018-004476-35-RO
• Date of registration: 27/04/2022
• Prospective Registration: No
• Primary sponsor: Novartis Pharma AG
• Public title: Study of safety and efficacy of multiple doses of CFZ533 in two distinct populations of patients with Sjögren’s Syndrome
• Scientific 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 Sjögren’s Syndrome (TWINSS) - TWINSS
• Date of first enrolment: 11/08/2020
• Target sample size: 260
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004476-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 6
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Brazil, Canada, Chile, Colombia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Portugal, Romania, Russian Federation, Slovenia, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: Simona Nedelcovici
• Affiliation: Novartis Pharma Services Romania S.R.L.

• Name: Simona Nedelcovici
• Affiliation: Novartis Pharma Services Romania S.R.L.

Key inclusion & exclusion 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

Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 221
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 39

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 allowe 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.

Other protocol-defined exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Sjögren syndrome
MedDRA version: 21.0 Level: PT Classification code 10040767 Term: Sjogren's syndrome System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: iscalimab
Product Code: CFZ533
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: iscalimab
Current Sponsor code: CFZ533
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: Cohort 1
To demonstrate a dose-response of CFZ533 (iscalimab) based on change in ESSDAI from baseline at Week 24.

Cohort 2
To estimate the effect of CFZ533 (iscalimab) on the change in ESSPRI at Week 24.

Primary end point(s): 1) Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo [ Time Frame: 24 weeks ]
Cohort 1 - Efficacy

2) Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score from baseline at 24 weeks as compared to placebo. [ Time Frame: 24 weeks ]
Cohort 2 - Efficacy

Timepoint(s) of evaluation of this end point: 1) at Baseline and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 40, 48, 52, 56, 60
2) at Baseline and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 40, 48

Secondary Objective: Cohort 1
To demonstrate a dose response of iscalimab based on change in ESSPRI from baseline at Week 24

Cohort 2
To estimate the effects of iscalimab based on changes in ESSDAI from baseline at Week 24
To evaluate the efficacy of iscalimab in improving the dry eye symptoms measured by IDEEL at Week 24

Cohort 1 & 2
To estimate the effects of iscalimab based on:
- change in FACIT-F from baseline at Week 24
- change in physician's global assessment (PhGA) from baseline at Week 24
To assess:
- the effect of iscalimab in the serum Free Light Chains (FLC) levels over time
- the changes in IgG and IgM levels over time after iscalimab treatment
- the effect of iscalimab on plasma CXCL-13 over time
To assess:
- safety and tolerability of iscalimab
- immunogenicity of iscalimab
- the pharmacokinetics and dose-exposure relationship of iscalimab
To measure soluble CD40 in plasma

Secondary Outcome(s)

Secondary end point(s): 1) Change from baseline in ESSPRI at Week 24 [ Time Frame: 24 weeks ]
Cohort 1 - Efficacy (Patient Reported Outcomes)

2) Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24 [ Time Frame: 24 weeks ]
Cohort 1&2 - Efficacy (Patient Reported Outcomes)

3) Change from baseline in Physician Global Assessment (PhGA) at Week 24 [ Time Frame: 24 weeks ]
Cohort 1&2 - Efficacy (Clinical Outcome Measures)

4) Change from baseline in ESSDAI at Week 24 [ Time Frame: 24 weeks ]
Cohort 2 - Efficacy (Clinical Outcome Measures)

5) 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. [ Time Frame: 24 weeks ]
Cohort 2 - Efficacy (Patient Reported Outcomes)

6) Incidence of adverse events (AEs), serious adverse events (SAEs) from baseline to Week 24 and from week 24 to the end of study [ Time Frame: 60 weeks ]
Cohort 1&2 - Safety

7) Serum Free Light Chain (FLC) levels at analysis visit up to end of study [ Time Frame: 60 weeks ]
Cohort 1&2 - Biomarkers (1)

8) Immunoglobulin IgG and IgM levels at analysis visits up to end of study [ Time Frame: 60 weeks ]
Cohort 1&2 - Biomarkers (2)

9) Percent change from baseline in plasma CXCL-13 levels at analysis visits up to end of study [ Time Frame: 60 weeks ]
Cohort 1&2 - Biomarkers (3)

Timepoint(s) of evaluation of this end point: 1), 2), 3), 4) at Baseline and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 40, 48
5), 8), 9) at Baseline and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 40, 48, 52, 56, 60
6) at baseline and repeatedly until study completion
7) at Baseline and at Weeks 4, 12, 24, 32, 48, 56, 60

Secondary ID(s)

2018-004476-35-PT

CCFZ533B2201

NCT03905525

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 27/04/2020
Contact: