Clinical trial NCT04802057: Safety and Tolerability Study in Adults With Cold Agglutinin Disease Previously Treated With SAR445088 or Never Treated With SAR445088
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Autoimmune Haemolytic Anaemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-03-17
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAE)
timeFrame: Day 1 or Day 1-IV to end of study, approximately 6 years
Secondary outcomes:
measure: Mean change from baseline in total bilirubin over time
timeFrame: Day 1 or Day 1-IV to end of study, approximately 6 years
measure: Mean change from baseline in hemoglobin over time
timeFrame: Day 1 or Day 1-IV to end of study, approximately 6 years
measure: Mean change from baseline in lactate dehydrogenase over time
timeFrame: Day 1 or Day 1-IV to end of study, approximately 6 years
measure: Mean change from baseline in reticulocyte count over time
timeFrame: Day 1 or Day 1-IV to end of study, approximately 6 years
measure: Complement System Classical Pathway Levels as Measured by WIESLAB Assay
timeFrame: Day 1 or Day 1-IV to Week 48-IV
measure: Complement System Alternative Pathway Levels as Measured by WIESLAB Assay
timeFrame: Day 1 to Week 24
measure: Mean change in CH50 over time
timeFrame: Day 1 or Day 1-IV to end of study, approximately 6 years
measure: Total Complement Factor C4 Levels
timeFrame: Day 1 or Day 1-IV to end of study, approximately 6 years
measure: PK parameter: Cmax
timeFrame: Day 1 or Day 1-IV to Week 48-IV
measure: PK Parameter: AUC
timeFrame: Day 1 or Day 1-IV to Week 48-IV
measure: Number of participants with anti-SAR445088 antibodies
timeFrame: Day 1 or Day 1-IV to end of study, approximately 6 years
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Investigational Site Number : 2760001
city: Milano
country: Italy
facility: Investigational Site Number : 3800001
city: Amsterdam
country: Netherlands
facility: Investigational Site Number : 5280001
city: Bergen
country: Norway
facility: Investigational Site Number : 5780001
city: London
country: United Kingdom
facility: Investigational Site Number : 8260001
state: London, City Of
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: