A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of the Safety, Tolerability, Pharmacokinetics, and Therapeutic Efficacy of SAR441344 in Adult Patients With Primary Sjögren's Syndrome (pSjS)
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 84
- Locations
- 36
- Primary Endpoint
- Change From Baseline to Week 12 in ESSDAI Score
Overview
Brief Summary
Primary Objective:
To evaluate the therapeutic efficacy of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with primary Sjögren's syndrome (pSjS), assessed by the change of the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI)
Secondary Objectives:
- To evaluate the therapeutic efficacy of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS
- To evaluate the therapeutic efficacy on fatigue of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS
- To evaluate the pharmacokinetic (PK) exposure of one dose level of SAR441344 over 12 weeks in adult patients with pSjS
- To evaluate the safety and tolerability of one dose level of SAR441344 versus placebo in adult patients with pSjS as determined by adverse events (AEs)
- To evaluate the local tolerability of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS
- To evaluate the safety and tolerability of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS determined by electrocardiogram, vital signs, and laboratory evaluations
- To measure the immunogenicity of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS
This is a multicenter, randomized, double blind, placebo controlled, parallel group proof of concept Phase 2 study to evaluate the therapeutic efficacy of SAR441344 in adult patients with primary Sjögren's syndrome (pSjS), as well as safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD).
- Study visit frequency: every 2 weeks in the treatment period and every 4 weeks in the follow-up period.
- The total duration of the study will be 24 weeks (28 weeks including maximum screening duration) for each participant, including a 12-week treatment period and a 12-week follow-up period.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent.
- •Diagnosis of pSjS according to the American College of Rheumatology/EULAR 2016 criteria at Screening.
- •Disease duration since first diagnosis of pSjS ≤15 years based on medical history.
- •Participants with moderate to severe disease activity set with ESSDAI total score ≥5, based on the following domains at Screening: glandular, articular, muscular, hematological, biological, and constitutional, lymphadenopathy.
- •Seropositive for anti-Ro/SSA antibodies.
- •IgG \> lower limit of normal (ULN) at Screening.
- •Stimulated salivary flow rate of ≥0.1 mL/min at Screening or Baseline.
- •Body weight within 45 to 120 kg (inclusive) and body mass index within the range of 18.0 to 35.0 kg/m2 (inclusive) at Screening.
- •Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Capable of giving signed informed consent.
Exclusion Criteria
- •Any autoimmune disease (except pSjS and Hashimoto thyroiditis) with or without secondary SjS.
- •History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphospholipid syndrome and any participants requiring antithrombotic treatment.
- •Active life threatening or organ threatening complications of pSjS disease at the time of Screening based on treating physician evaluation including but not restricted to:
- •Vasculitis with renal, digestive, cardiac, pulmonary, or CNS involvement characterized as severe,
- •Active central nervous system (CNS) or peripheral nervous system (PNS) involvement requiring high dose steroids,
- •Severe renal involvement defined by objective measures,
- •Lymphoma.
- •Cardiac heart failure Stage III or IV according to the New York Heart Association.
- •Severe pulmonary impairment documented by an abnormal pulmonary function test.
- •Serious systemic viral, bacterial or fungal infection (eg, pneumonia, pyelonephritis), infection requiring hospitalization or IV antibiotics or significant chronic viral (including history of recurrent or active herpes zoster), bacterial, or fungal infection (eg, osteomyelitis) 30 days before and during Screening.
Arms & Interventions
SAR441344
SAR441344 single intravenous (IV) loading dose on Day 1 followed by a single subcutaneous (SC) dose administered once every 2 weeks from Week 2 to Week 10 (5 administrations)
Intervention: SAR441344 (Drug)
Placebo
Matching placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change From Baseline to Week 12 in ESSDAI Score
Time Frame: Baseline (Day 1) to Week 12
ESSDAI is validated and established outcome measurement for therapeutic efficacy in Sjögren's syndrome, evaluating disease activity mainly on extra-glandular manifestations. This score consists of 12 organ-specific domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, muscular, peripheral and central nervous system, hematological, biological), which are scored based on organ-specific items in 3 to 4 different severity grades (no, low, moderate, high; with 0=no and 3=high). These scores are summed up over all 12 domains in weighted way (severity grades are multiplied with weights ranging 1-6 depending on domain) to summarize into total score(0-123). Higher scores indicates worse outcome. Negative change from baseline indicates improvement. Baseline=Day 1 assessment value. Least squares (LS) mean is calculated using mixed models for repeated measures (MMRM). Observed values after occurrence of intercurrent events are excluded.
Secondary Outcomes
- Change From Baseline to Week 12 in European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI) Score(Baseline (Day 1) to Week 12)
- Change From Baseline to Week 12 in Multidimensional Fatigue Inventory (MFI) General Fatigue Subscale and Other Subscales Score(Baseline (Day 1) to Week 12)
- Mean Plasma Concentration of SAR441344(At end of infusion and 4 hours post-infusion on Day 1; pre-dose at Weeks 2, 4, 6, 8, 10, and at Week 12)
- Median Plasma Concentration of SAR441344(At end of infusion and 4 hours post-infusion on Day 1; pre-dose at Weeks 2, 4, 6, 8, 10, and at Week 12)
- Maximum Plasma Concentration (Cmax) of SAR441344(After the last SC dose on Week 10 up to 336 hours post-dose)
- Time to Maximum Plasma Concentration (Tmax) of SAR441344(After the last SC dose on Week 10 up to 336 hours post-dose)
- Area Under the Curve Over the Dosing Interval (AUC0-tau) of SAR441344(After the last SC dose on Week 10 up to 336 hours post-dose)
- Terminal Half-life (t1/2z) of SAR441344(Week 10 to Week 12)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events of Special Interest (AESI)(From first dose of IMP (Day 1) up to end of follow-up period (Week 24))
- Number of Participants With Treatment Discontinuation and Withdrawals Due to TEAEs(From first dose of IMP (Day 1) up to end of follow-up period (Week 24))
- Number of Participants With Increase in Pain Intensity Compared to Pre-dose Pain Intensity at Injection Site by Verbal Descriptor Scale (VDS)(Pre-dose (within 24 hours prior IMP dosing), post-dose (up to 15 minutes after dosing) and 2 hours post-dose at Weeks 2, 4, 6, 8 and 10)
- Number of Participants With AEs Related to Local Tolerability Findings(Baseline (Day 1) to Week 10)
- Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs(Baseline (Day 1) to Week 24)
- Number of Participants With PCSA in Electrocardiogram(Baseline (Day 1) to Week 24)
- Number of Participants With PCSA in Hematology Parameters(Baseline (Day 1) to Week 24)
- Number of Participants With PCSA in Clinical Chemistry Parameters(Baseline (Day 1) to Week 24)
- Number of Participants With PCSA in Urinalysis Parameters(Baseline (Day 1) to Week 24)
- Number of Participants With Anti-drug Antibodies (ADA) to SAR441344(Baseline, Week 4, Week 8, Week 12, and Week 24)