Clinical trial NCT04269551: A Safety and Tolerability Study of BIVV020 in Adults With Cold Agglutinin Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Autoimmune Haemolytic Anaemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-02-17
Enrollment: 12
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 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)

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of adverse events (AEs)
timeFrame: Screening to Day 106
Secondary outcomes:
measure: Mean change from baseline in bilirubin over time
timeFrame: Day 1 to Day 106
measure: Mean change from baseline in hemoglobin over time
timeFrame: Day 1 to Day 106
measure: Complement System Classical Pathway Levels as Measured by WIESLAB Assay
timeFrame: Day 1 to Day 106
measure: Complement System Alternative Pathway Levels as Measured by WIESLAB Assay
timeFrame: Day 1 to Day 106
measure: Total Complement (CH50) Levels
timeFrame: Day 1 to Day 106
measure: Total Complement Factor C4 Levels
timeFrame: Day 1 to Day 106
measure: PK parameter: Cmax
timeFrame: Day 1 to Day 106
measure: PK parameter: tmax
timeFrame: Day 1 to Day 106
measure: PK parameter: AUClast
timeFrame: Day 1 to Day 106
measure: PK parameter: AUC0-∞
timeFrame: Day 1 to Day 106
measure: Number of participants with anti-BIVV antibodies
timeFrame: Day 1 to Day 106
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Investigational Site Number :8400002
state: Georgia
city: Saint Louis
country: United States
facility: Investigational Site Number :8400009
state: Missouri
city: Bronx
country: United States
facility: Investigational Site Number :8400006
state: New York
city: Pittsburgh
country: United States
facility: Investigational Site Number :8400008
state: Pennsylvania
city: Seattle
country: United States
facility: Investigational Site Number :8400004
state: Washington
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: