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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Autoimmune Haemolytic Anaemia
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 45147
    • Investigational Site Number : 2760001
• Italy
  • Milano, Italy, 20122
    • Investigational Site Number : 3800001
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Investigational Site Number : 5280001
• Norway
  • Bergen, Norway, 5021
    • Investigational Site Number : 5780001
• United Kingdom
  • London, City Of
    • London, London, City Of, United Kingdom, NW1 2PG
      • Investigational Site Number : 8260001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR445088; Repeat dose of SAR445088	Drug: SAR445088; Pharmaceutical form: solution for injection Route of administration: IV and SC (Part 1) IV (Part 2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Mean change from baseline in hemoglobin over time	Assessment of hemoglobin	Day 1 or Day 1-IV to end of study, approximately 6 years
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
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
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
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
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
PK parameter: Cmax	Maximum observed concentration (Cmax) of SAR445088 in plasma will be assessed	Day 1 or Day 1-IV to Week 48-IV
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
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

Collaborators and Investigators

• Sponsor: Bioverativ, a Sanofi company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Estimated): January 23, 2026
• Study Completion (Estimated): January 23, 2026

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 17, 2021

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: LTS16637; 2019-004423-21 (EudraCT Number); U1111-1244-0808 (Registry Identifier: ICTRP); 2023-510210-68 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes