The primary objective of this study is to evaluate the safety and tolerability of iscalimab at two dose levels (600 mg and 300 mg) in patients withSjögren*s Syndrome, who participated in the TWINSS core study,CCFZ533B2201.Secondary…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Incidence of Treatment-emergent adverse events (TEAEs)/ serious adverse
events (SAEs)
- Routine hematology and clinical chemistry laboratory test results at analysis
visits up to end of study
- Vital signs at analysis visits up to end of study
Secondary outcome
- Free iscalimab concentration in plasma during the treatment (Ctrough) and
follow-up (up to end of study) periods
- Incidence of anti-iscalimab antibodies in plasma at analysis visits up to end
of study
- The full list of exploratory endpoints to be included in the Clinical Study
Report (CSR) and corresponding analysis methods will be
detailed in the Statistical Analysis Plan (SAP)
- Biomarker levels during the treatment and follow-up (up to end of study)
periods
- Free or total soluble CD40 in the absence or presence of iscalimab,
respectively, at analysis visits up to end of study
-Biomarker levels during the treatment and follow-up (up to end of study)
periods
- Physical activity and vital sign parameters levels as measured with wearable
device during the treatment and follow-up (up to end of study) periods
Patient Health Questionnaire-2 (PHQ-2) total score and cognitive tests scores
as measured with smartphone application during the treatment and follow-up (up
to end of study) periods
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.
Limited safety data are currently available for iscalimab in any indication
that is under investigation. This extension study (CCFZ533B2201E1) will allow
us to demonstrate the additional safety and tolerability of two doses (600 mg
and 300 mg) of treatment with iscalimab in patients with Sjögren's Syndrome
(SjS).
Study objective
The primary objective of this study is to evaluate the safety and tolerability
of iscalimab at two dose levels (600 mg and 300 mg) in patients with
Sjögren*s Syndrome, who participated in the TWINSS core study,CCFZ533B2201.
Secondary Objectives
Objective 1: To assess the pharmacokinetics (PK trough levels) and dose
exposure relationship of iscalimab
Objective 2: To assess immunogenicity of iscalimab
Study design
Study CCFZ533B2201E1 is a multicenter extension study. Study blinding for the
extension study will be maintained until final database lock of the
core study, CCFZ533B2201, upon which the participants and Investigators will be
unblinded, making it an open-label study through Week 120 (end of
study visit).
Intervention
CFZ533
Study burden and risks
Minimum of 28 visits, duration vary from 1-3 hours per visit, total study time
30 months.
Physical examination: 15 times
ECG: 1 time
Questionnaires: 7 times
Patient diary: completion every week
Arm- worn wearable device: To measure physical activity (optional): 7 times
Cognitive assessments: 7 times
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
1. Participants must have participated in the TWINSS core study, CCFZ533B2201,
and must have completed the entire treatment period up to Week 48 and the
follow-up period up to Week 60
2. Signed informed consent must be obtained prior to participation in the
extension study (i.e. before commencement of the Week 60 assessments of the
core study)
3. In the judgement of the Investigator, participants must be expected to
clinically benefit from continued iscalimab therapy
Exclusion criteria
1. Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic
disease constitutes the principle illness, specifically:
Moderate-to-severe active systemic lupus erythematosus (SLE) with anti-dsDNA
positivity and renal involvement, or other organ involvement that impedes on
ability to score ESSDAI domains
- Active rheumatoid arthritis (RA) that impedes on the ability to score the
ESSDAI articular domain
- Systemic sclerosis
- Any other concurrent connective tissue disease (e.g., lupus nephritis (LN),
large vessel vasculitis (LVV), Sharp syndrome (mixed connective tissue disease)
that is active and requires immunosuppressive treatment outside the scope of
this trial and would impede on Sjögren's Syndrome organ domain assessments
2. Use of other investigational drugs other than iscalimab during the core study
3. Active uncontrolled viral, bacterial or other infections requiring systemic
treatment at the time of enrollment, or history of recurrent clinically
significant infection or of bacterial infections with encapsulated organisms
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 | EUCTR2020-001942-20-NL |
| ClinicalTrials.gov | NCT04541589 |
| CCMO | NL77019.078.21 |