Safety and Tolerability Study in Adults With Cold Agglutinin Disease Previously Treated With SAR445088 or Never Treated With SAR445088

Autoimmune Haemolytic Anaemia Clinical Trial

Official title:

An Open-label, Long-term, Safety and Tolerability Study of SAR445088 in Participants With Cold Agglutinin Disease Previously Treated With SAR445088 or Never Treated With SAR445088

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04802057
• Other study ID #: LTS16637
• Secondary ID: U1111-1244-08082
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 22, 2021
• Est. completion date: January 23, 2026

Study information

• Verified date: February 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 9
• Est. completion date: January 23, 2026
• Est. primary completion date: January 23, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Autoimmune Haemolytic Anaemia

Intervention

Drug:
• SAR445088
Pharmaceutical form: solution for injection Route of administration: IV and SC (Part 1) IV (Part 2)

Locations

Country	Name	City	State
Germany	Investigational Site Number : 2760001	Essen
Italy	Investigational Site Number : 3800001	Milano
Netherlands	Investigational Site Number : 5280001	Amsterdam
Norway	Investigational Site Number : 5780001	Bergen
United Kingdom	Investigational Site Number : 8260001	London	London, City Of

Sponsors (1)

Lead Sponsor	Collaborator
Bioverativ, a Sanofi company

Countries where clinical trial is conducted

Germany,  Italy,  Netherlands,  Norway,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-emergent adverse events (TEAE)	The number of participants experiencing TEAEs will be reported for the overall safety population.	Day 1 or Day 1-IV to end of study, approximately 6 years
Secondary	Mean change from baseline in total bilirubin over time	Assessment of total bilirubin	Day 1 or Day 1-IV to end of study, approximately 6 years
Secondary	Mean change from baseline in hemoglobin over time	Assessment of hemoglobin	Day 1 or Day 1-IV to end of study, approximately 6 years
Secondary	Mean change from baseline in lactate dehydrogenase over time	Assessment of lactate dehydrogenase	Day 1 or Day 1-IV to end of study, approximately 6 years
Secondary	Mean change from baseline in reticulocyte count over time	Assessment of reticulocyte count	Day 1 or Day 1-IV to end of study, approximately 6 years
Secondary	Complement System Classical Pathway Levels as Measured by WIESLAB Assay	Inhibition by SAR445088 of the complement system classical pathway measured by the WIESLAB assay.	Day 1 or Day 1-IV to Week 48-IV
Secondary	Complement System Alternative Pathway Levels as Measured by WIESLAB Assay	Part 1: Effect of SAR445088 on the complement system alternative pathway measured by the WIESLAB assay.	Day 1 to Week 24
Secondary	Mean change in CH50 over time	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.	Day 1 or Day 1-IV to end of study, approximately 6 years
Secondary	Total Complement Factor C4 Levels	Total C4 Levels will be assessed in plasma using complement assays	Day 1 or Day 1-IV to end of study, approximately 6 years
Secondary	PK parameter: Cmax	Maximum observed concentration (Cmax) of SAR445088 in plasma will be assessed	Day 1 or Day 1-IV to Week 48-IV
Secondary	PK Parameter: AUC	Area under the plasma concentration versus time curve calculated using the trapezoidal method at steady state	Day 1 or Day 1-IV to Week 48-IV
Secondary	Number of participants with anti-SAR445088 antibodies	The immunogenicity for SAR445088 will be assessed by summarizing the number of participants with anti-SAR445088 antibodies (ADA)	Day 1 or Day 1-IV to end of study, approximately 6 years