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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bioverativ USA Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

26 May 2021 → 4 Mar 2025

Decision date (initial)

2024-02-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-510210-68-00

EudraCT number

2019-004423-21

WHO UTN

U1111-1244-0808

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy, Pharmacodynamic, Pharmacokinetic

To assess the long-term safety and tolerability in patients with cold agglutinin disease (CAD), after multiple doses of SAR445088

Secondary objectives 1

1. 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

Conditions and MedDRA coding

Autoimmune haemolytic anaemia

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002903-PIP02-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 1

1. Participants are excluded from the study if any of the following criteria apply: 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of participants with treatment-emergent adverse events (TEAE)

Secondary endpoints 11

1. Mean change from baseline in total bilirubin over time
2. Mean change from baseline in hemoglobin over time
3. Mean change from baseline in lactate dehydrogenase over time
4. Mean change from baseline in reticulocyte count over time
5. Complement System Classical Pathway Levels as Measured by WIESLAB Assay
6. Complement System Alternative Pathway Levels as Measured by WIESLAB Assay
7. Mean change in CH50 over time
8. Total Complement Factor C4 Levels
9. PK parameter: Cmax
10. PK Parameter: AUC
11. Number of participants with anti-SAR445088 antibodies

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bioverativ USA Inc.

Sponsor organisation

Bioverativ USA Inc.

Address

225 Second Avenue

City

Waltham

Postcode

02451-1122

Country

United States

Scientific contact point

Organisation

Bioverativ USA Inc.

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Bioverativ USA Inc.

Contact name

Clinical Sciences and Operations

Third parties 3

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications