Autoimmune Haemolytic Anaemia
Conditions
Brief 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
Detailed description
Up to 23 weeks (screening period up to 8 weeks, treatment period 15 weeks)
Interventions
DRUGBIVV020
Pharmaceutical form:solution for injection Route of administration: intravenous
Sponsors
Bioverativ, a Sanofi company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of adverse events (AEs) | Screening to Day 106 | Number of participants with adverse events (AEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in hemoglobin over time | Day 1 to Day 106 | Assessment of hemoglobin |
| Complement System Classical Pathway Levels as Measured by WIESLAB Assay | Day 1 to Day 106 | Inhibition by BIVV020 of the complement system classical pathway measured by the WIESLAB assay |
| Complement System Alternative Pathway Levels as Measured by WIESLAB Assay | Day 1 to Day 106 | Effect of BIVV0020 on the complement system alternative pathway measured by the WIESLAB assay |
| Total Complement (CH50) Levels | Day 1 to Day 106 | 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. |
| Total Complement Factor C4 Levels | Day 1 to Day 106 | Total C4 Levels will be assessed in plasma using complement assays |
| Mean change from baseline in bilirubin over time | Day 1 to Day 106 | Assessment of total bilirubin |
| PK parameter: tmax | Day 1 to Day 106 | Observed first time to reach Cmax |
| PK parameter: AUClast | Day 1 to Day 106 | Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast |
| PK parameter: AUC0-∞ | Day 1 to Day 106 | Calculated area under the plasma concentration versus time curve extrapolated to infinity |
| Number of participants with anti-BIVV antibodies | Day 1 to Day 106 | Observed number of participants with BIVV020 antibodies |
| PK parameter: Cmax | Day 1 to Day 106 | Observed maximum plasma concentration |
Countries
Germany, Italy, Netherlands, Norway, United Kingdom, United States
Outcome results
None listed