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

Novartis

Status and phase: Completed; Phase 2

Conditions: Sjögren Syndrome

Treatments: Drug: CFZ533; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03905525

CCFZ533B2201

2018-004476-35 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 273 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

273 participants in 8 patient groups, including a placebo group

Cohort 1 /Arm A

Experimental group

Description:

CFZ533 dose 1

Treatment:

Drug: CFZ533

Cohort 1/Arm B

Experimental group

Description:

CFZ533 dose 2

Treatment:

Drug: CFZ533

Cohort 1/Arm C

Experimental group

Description:

CFZ533 dose 3

Treatment:

Drug: CFZ533

Cohort 1/Arm D

Placebo Comparator group

Description:

Placebo dose (up to week 24)

Treatment:

Other: Placebo

Cohort 1/Arm D1

Experimental group

Description:

CFZ533 dose 1 (from week 24)

Treatment:

Drug: CFZ533

Cohort 2/Arm E

Experimental group

Description:

CFZ533 dose 1

Treatment:

Drug: CFZ533

Cohort 2/Arm F

Placebo Comparator group

Description:

Placebo dose (up to week 24)

Treatment:

Other: Placebo

Cohort 2/Arm F1

Experimental group

Description:

CFZ533 dose 2 (from week 24)

Treatment:

Drug: CFZ533