A Safety and Tolerability Study of BIVV020 in Adults With Cold Agglutinin Disease

Autoimmune Haemolytic Anaemia Clinical Trial

Official title:

A Multicenter, Phase 1b, Open Label, Nonrandomized, Single Dose Study Evaluating the Safety, Tolerability and Activity of BIVV020 in Adults With Cold Agglutinin Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04269551
• Other study ID #: PDY16370
• Secondary ID: 2019-001844-22U1
• Status: Completed
• Phase: Phase 1
• Start date: June 15, 2020
• Est. completion date: January 6, 2022

Study information

• Verified date: April 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective: To assess the safety and tolerability in participants with cold agglutinin disease (CAD), after a single dose of intravenous (IV) BIVV020 Secondary Objectives: To assess, in participants with cold agglutinin disease, after a single dose of intravenous (IV) BIVV020: - The effect of BIVV020 on complement mediated hemolysis - The pharmacodynamics (PD) of BIVV020 relating to complement inhibition - The pharmacokinetics (PK) of BIVV020 - The immunogenicity of BIVV020

Description:

Up to 23 weeks (screening period up to 8 weeks, treatment period 15 weeks)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 6, 2022
• Est. primary completion date: January 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Male and/or female patients, = 18 years of age with cold agglutinin disease as defined

by:

1. Chronic hemolysis per Investigator's judgement,

2. Polyspecific direct antiglobulin test (DAT) positive,

3. Monospecific DAT strongly positive for C3d,

4. Cold agglutinin (CAg) titer = 64 at 4 C; and,

5. IgG DAT =1+.

• A hemoglobin level =11 mg/dL.
• A total bilirubin level above the normal reference range that is thought to be due to hemolysis.
• Documented vaccinations against encapsulated bacterial pathogens (Neisseria meningitidis, including serogroup B meningococcus and Streptococcus pneumoniae) within five years of screening or willing to complete protocol specified vaccinations.
• 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 of any kind within one month preceding screening.
• Treatment with anti-CD20 monotherapy within three months or anti CD20 combination therapies within six 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 within three months prior to screening.
• Concurrent treatment with systemic corticosteroids other than a stable daily dose equivalent to =10 mg/day prednisone within three months prior to screening.
• If female, pregnant or lactating. 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:
• BIVV020
Pharmaceutical form:solution for injection Route of administration: intravenous

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
United States	Investigational Site Number :8400006	Bronx	New York
United States	Investigational Site Number :8400002	Fayetteville	Georgia
United States	Investigational Site Number :8400008	Pittsburgh	Pennsylvania
United States	Investigational Site Number :8400009	Saint Louis	Missouri
United States	Investigational Site Number :8400004	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Bioverativ, a Sanofi company

Countries where clinical trial is conducted

United States,  Germany,  Italy,  Netherlands,  Norway,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of adverse events (AEs)	Number of participants with adverse events (AEs)	Screening to Day 106
Secondary	Mean change from baseline in bilirubin over time	Assessment of total bilirubin	Day 1 to Day 106
Secondary	Mean change from baseline in hemoglobin over time	Assessment of hemoglobin	Day 1 to Day 106
Secondary	Complement System Classical Pathway Levels as Measured by WIESLAB Assay	Inhibition by BIVV020 of the complement system classical pathway measured by the WIESLAB assay	Day 1 to Day 106
Secondary	Complement System Alternative Pathway Levels as Measured by WIESLAB Assay	Effect of BIVV0020 on the complement system alternative pathway measured by the WIESLAB assay	Day 1 to Day 106
Secondary	Total Complement (CH50) Levels	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 to Day 106
Secondary	Total Complement Factor C4 Levels	Total C4 Levels will be assessed in plasma using complement assays	Day 1 to Day 106
Secondary	PK parameter: Cmax	Observed maximum plasma concentration	Day 1 to Day 106
Secondary	PK parameter: tmax	Observed first time to reach Cmax	Day 1 to Day 106
Secondary	PK parameter: AUClast	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast	Day 1 to Day 106
Secondary	PK parameter: AUC0-8	Calculated area under the plasma concentration versus time curve extrapolated to infinity	Day 1 to Day 106
Secondary	Number of participants with anti-BIVV antibodies	Observed number of participants with BIVV020 antibodies	Day 1 to Day 106