The purpose of this trial is to- determine the dose-response of iscalimab in a population of patients with moderate-to-severe Sjögren*s Syndrome (SjS), defined by ESSDAI >=5and ESSPRI >=5 (Cohort 1)- evaluate the preliminary efficacy and…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objectives of the study are defined separately for each cohort.
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) 600 mg s.c. on the change in
ESSPRI at Week 24.
Secondary outcome
Cohort 1
To demonstrate a dose response of iscalimab based on change in ESSPRI from
baseline at Week 24
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.
Cohort 2
To estimate the effects of iscalimab based on changes in
- FACIT-F from baseline at Week 24
- Physician's global assessments from baseline at Week 24
- ESSDAI from baseline at Week 24
To evaluate the efficacy of iscalimab in improving the dry eye
symptoms measured by IDEEL 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.
Cohort 1 & 2
To assess
- safety and tolerability of iscalimab
- immunogenicity of iscalimab
- the pharmacokinetics and dose-exposure relationship of iscalimab
To measure soluble CD40 in plasma
Background summary
Sjögren*s Syndrome (SjS) is a chronic autoimmune disease of unknown etiology,
characterized by lymphoid
infiltration and progressive destruction of exocrine glands. Current
standard-of-care (SoC) treatment for SjS patients is
limited to symptomatic care for the mucosal signs and symptoms (dryness).
Steroids and conventional disease
modifying antirheumatic drugs (DMARDs), although used in selected patients,
have not been proven efficacious, and
no pharmacologic intervention is effective against the severe, disabling
fatigue. Hence, there are no approved
treatments available for active, systemic disease.
The therapeutic hypothesis was successfully tested in a first proof-of-concept
(PoC) study of
iscalimab in patients with primary Sjögren's Syndrome. Briefly, in this
randomized controlled
trial, the primary endpoint of European Sjögren*s Syndrome Disease Activity
Index (ESSDAI)
improvement was met, along with improvements in patient reported outcomes (PRO)
including
fatigue. The overall risk/benefit profile was favorable, warranting continued
development in this indication.
Study objective
The purpose of this trial is to
- determine the dose-response of iscalimab in a population of patients with
moderate-to-severe Sjögren*s Syndrome (SjS), defined by ESSDAI >=5
and ESSPRI >=5 (Cohort 1)
- evaluate the preliminary efficacy and safety of iscalimab administered in a
population of patients with low ESSDAI (<5) but high symptom burden
(Cohort 2) defined by: ESSPRI fatigue >=5 or ESSPRI dryness >=5 and moderate
ocular disease burden as measured by the Impact of Dry Eye on Everyday Life
(IDEEL) questionnaire.
Study design
Study CFZ533B2201 (TWINSS) is a double-blind, randomized, placebocontrolled,
multicenter study to evaluate the safety, efficacy, PK and PD of
multiple doses of CFZ533 in 2 distinct populations of patients with 1)
moderate-to-severe SjS (systemic and symptomatic involvement) and 2)
low systemic involvement but high symptom burden.
Intervention
CFZ533 or placebo
Study burden and risks
Minimum of 31 visits, duration vary from 1-4 hours per visit, total study time
minimal 66 weeks.
Physical examination: Cohort 1: 15 times Cohort 2: 16 times
ECG: Cohort 1:one time, Cohort 2: One time
Schirmer test: Cohort 1: 6 times, Cohort 2: 6 times
Salivary flow rate (unstimulated ) cohort 1: 5 times and cohort 2: 5 times
Stimulated Cohort 1: 9 times Cohort 2: 9 times
Salivary gland biopsy (optional): Cohort 1 and Cohort 2: 2 times
Questionnaires: Cohort1:25 times Cohort 2: 25 times
Patient diary: cohort 1: 27 times, cohort 2: 27 times
Arm- worn wearable device: To measure physical activity (optional): cohort 1
and 2: 8 times
Cognitive assessments: cohort 1: 4 times cohort 2: 4 times
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
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 #7 Cohort 1;
•ESSPRI fatigue subscore >= 5 or ESSPRI dryness subscore >= 5;
Other protocol-defined inclusion criteria may apply.
Exclusion criteria
•Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic
disease constitutes the principle illness;
•Use of other investigational drugs;
•Use of B cell depleting therapies within 6 months prior to randomization,
abatacept or any other immunosuppressants unless specifically allowed in 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, during treatment and for at least 14 weeks thereafter;
•Chronic infection with hepatitis B (HBV) or hepatitis C (HCV);
- Evidence of active CMV infection in the form of a positive serology for
CMV IgM (in the absence or presence of positive CMV IgG) and/or
quantifiable CMV DNA by PCR at screening.
•Evidence of active tuberculosis (TB) infection.
Other protocol-defined exclusion criteria may apply.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-004476-35-NL |
| ClinicalTrials.gov | NCT03905525 |
| CCMO | NL69847.078.19 |