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

• ClinicalTrials.gov Identifier: NCT04802057
• Recruitment Status: Active, not recruiting
• First Posted: March 17, 2021
• Last Update Posted: August 24, 2023
• Sponsor: Bioverativ, a Sanofi company
• Information provided by (Responsible Party): Sanofi ( Bioverativ, a Sanofi company )

Study Description

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

Condition or disease	Intervention/treatment	Phase
Autoimmune Haemolytic Anaemia	Drug: SAR445088	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 22, 2021
• Estimated Primary Completion Date: June 16, 2028
• Estimated Study Completion Date: June 16, 2028

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-emergent adverse events (TEAE) [ Time Frame: 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 :

1. Mean change from baseline in total bilirubin over time [ Time Frame: Day 1 or Day 1-IV to end of study, approximately 6 years ]
   Assessment of total bilirubin
2. Mean change from baseline in hemoglobin over time [ Time Frame: Day 1 or Day 1-IV to end of study, approximately 6 years ]
   Assessment of hemoglobin
3. Mean change from baseline in lactate dehydrogenase over time [ Time Frame: Day 1 or Day 1-IV to end of study, approximately 6 years ]
   Assessment of lactate dehydrogenase
4. Mean change from baseline in reticulocyte count over time [ Time Frame: Day 1 or Day 1-IV to end of study, approximately 6 years ]
   Assessment of reticulocyte count
5. Complement System Classical Pathway Levels as Measured by WIESLAB Assay [ Time Frame: Day 1 or Day 1-IV to Week 48-IV ]
   Inhibition by SAR445088 of the complement system classical pathway measured by the WIESLAB assay.
6. Complement System Alternative Pathway Levels as Measured by WIESLAB Assay [ Time Frame: Day 1 to Week 24 ]
   Part 1: Effect of SAR445088 on the complement system alternative pathway measured by the WIESLAB assay.
7. Mean change in CH50 over time [ Time Frame: 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.
8. Total Complement Factor C4 Levels [ Time Frame: Day 1 or Day 1-IV to end of study, approximately 6 years ]
   Total C4 Levels will be assessed in plasma using complement assays
9. PK parameter: Cmax [ Time Frame: Day 1 or Day 1-IV to Week 48-IV ]
   Maximum observed concentration (Cmax) of SAR445088 in plasma will be assessed
10. PK Parameter: AUC [ Time Frame: 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
11. Number of participants with anti-SAR445088 antibodies [ Time Frame: 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)

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Germany

Investigational Site Number :2760001

Essen, Germany, 45147

Italy

Investigational Site Number :3800001

Milano, Italy, 20122

Netherlands

Investigational Site Number :5280001

Amsterdam, Netherlands, 1105AZ

Norway

Investigational Site Number :5780001

Bergen, Norway, 5021

United Kingdom

Investigational Site Number :8260001

London, London, City Of, United Kingdom, NW1 2PG

Sponsors and Collaborators

Bioverativ, a Sanofi company

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Bioverativ, a Sanofi company
• ClinicalTrials.gov Identifier: NCT04802057
• Other Study ID Numbers: LTS16637; 2019-004423-21 ( EudraCT Number ); U1111-1244-0808 ( Registry Identifier: UTN )
• First Posted: March 17, 2021
• Last Update Posted: August 24, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• 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

Additional relevant MeSH terms:

Anemia, Hemolytic, Autoimmune; Anemia, Hemolytic; Anemia; Hematologic Diseases; Autoimmune Diseases; Immune System Diseases