Safety and Tolerability Study in Adults With Cold Agglutinin Disease Previously Treated With SAR445088 or Never Treated With SAR445088
- Registration Number
- NCT04802057
- Lead Sponsor
- Bioverativ, a Sanofi company
- Brief Summary
Primary Objective:
To assess the long-term safety and tolerability in patients with cold agglutinin disease (CAD), after multiple doses of SAR445088
Secondary Objective:
To assess, in patients with cold agglutinin disease (CAD), after multiple doses of SAR445088:
* The long-term effect of SAR445088 on complement mediated hemolysis
* The long-term pharmacodynamics (PD) effect of SAR445088 relating to complement inhibition
* The long-term pharmacokinetic (PK) profile of SAR445088
* The long-term immunogenicity of SAR445088
- Detailed Description
The screening period for this study is up to 6 weeks. The treatment period for this study will continue for 2 years after last participant entered Part 2 (either having switched from Part 1 or as a SAR445088-naïve participant), or until SAR445088 development is discontinued, whichever comes first.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 9
-
Male and female adult patients ≥18 years of age with CAD who were previously treated with SAR445088 and met criteria the below criteria for entry into Part 1:
- met the eligibility criteria of a previous study evaluating SAR445088;
- successfully enrolled and completed dosing in a previous study evaluating SAR445088;
- successfully completed end of study procedures in a previous study evaluating SAR445088; and
- per Investigator judgement, had a favorable benefit-to-risk profile after receiving SAR445088.
-
OR were never treated with SAR445088 before entering Part 2, and met the below criteria to establish CAD diagnosis:
- chronic hemolysis;
- polyspecific direct antiglobulin test (DAT) positive status;
- monospecific DAT strongly positive for C3d;
- cold agglutinin [CAg] titer ≥64 at 4°C;
- IgG DAT ≤1+;
- hemoglobin level ≤10 g/dL;
- elevated bilirubin not attributable to liver disease;
-
Documented vaccinations against encapsulated bacterial pathogens given within five years of enrollment and at least 14 days prior to dosing (vaccinations have to be initiated at least 14 days prior to dosing and completed before Week 5 of Part 2).
-
Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
-
Having given written informed consent prior to undertaking any study-related procedure.
- Cold agglutinin syndrome secondary to infection, rheumatologic disease, or known high-grade hematologic malignancy, or known solid organ tumor.
- Clinically relevant infection within 1 month of enrollment.
- Clinical diagnosis of systemic lupus erythematosus (SLE).
- Treatment with anti-CD20 monotherapy within 3 months or anti-CD20 combination therapies within 6 months prior to screening.
- Concurrent treatment with systemic immunosuppressive agents targeting B- or T-cell function and/or cytotoxic agents within 3 months prior to screening. Concurrent treatment with other systemic immunosuppressants within 5.5 half-lives of the drug prior to screening.
- Any specific complement system inhibitor other than SAR445088 (eg, eculizumab) within 3 months prior to screening.
- Concurrent treatment with systemic corticosteroids other than a stable daily dose equivalent to ≤10 mg/day prednisone within 3 months prior to screening.
- History of hypersensitivity to SAR445088 or any of its components.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SAR445088 SAR445088 Repeat dose of SAR445088
- Primary Outcome Measures
Name Time Method Number of participants with treatment-emergent adverse events (TEAE) Day 1 or Day 1-IV to end of study, approximately 6 years The number of participants experiencing TEAEs will be reported for the overall safety population.
- Secondary Outcome Measures
Name Time Method Mean change from baseline in total bilirubin over time Day 1 or Day 1-IV to end of study, approximately 6 years Assessment of total bilirubin
Mean change from baseline in hemoglobin over time Day 1 or Day 1-IV to end of study, approximately 6 years Assessment of hemoglobin
Mean change from baseline in lactate dehydrogenase over time Day 1 or Day 1-IV to end of study, approximately 6 years Assessment of lactate dehydrogenase
Mean change from baseline in reticulocyte count over time Day 1 or Day 1-IV to end of study, approximately 6 years Assessment of reticulocyte count
Total Complement Factor C4 Levels Day 1 or Day 1-IV to end of study, approximately 6 years Total C4 Levels will be assessed in plasma using complement assays
PK parameter: Cmax Day 1 or Day 1-IV to Week 48-IV Maximum observed concentration (Cmax) of SAR445088 in plasma will be assessed
Complement System Classical Pathway Levels as Measured by WIESLAB Assay Day 1 or Day 1-IV to Week 48-IV Inhibition by SAR445088 of the complement system classical pathway measured by the WIESLAB assay.
Complement System Alternative Pathway Levels as Measured by WIESLAB Assay Day 1 to Week 24 Part 1: Effect of SAR445088 on the complement system alternative pathway measured by the WIESLAB assay.
Number of participants with anti-SAR445088 antibodies Day 1 or Day 1-IV to end of study, approximately 6 years The immunogenicity for SAR445088 will be assessed by summarizing the number of participants with anti-SAR445088 antibodies (ADA)
Mean change in CH50 over time Day 1 or Day 1-IV to end of study, approximately 6 years Complement CH50 is a blood test that helps us determine whether protein abnormalities and deficiencies in the complement system are responsible for any increase in autoimmune activity. It will be assessed using complement assays.
PK Parameter: AUC Day 1 or Day 1-IV to Week 48-IV Area under the plasma concentration versus time curve calculated using the trapezoidal method at steady state
Trial Locations
- Locations (5)
Investigational Site Number : 8260001
🇬🇧London, London, City Of, United Kingdom
Investigational Site Number : 5780001
🇳🇴Bergen, Norway
Investigational Site Number : 3800001
🇮🇹Milano, Italy
Investigational Site Number : 2760001
🇩🇪Essen, Germany
Investigational Site Number : 5280001
🇳🇱Amsterdam, Netherlands