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

Primary Purpose

Autoimmune Haemolytic Anaemia

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BIVV020
Sponsored by
Bioverativ, a Sanofi company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autoimmune Haemolytic Anaemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number :8400002
  • Investigational Site Number :8400009
  • Investigational Site Number :8400006
  • Investigational Site Number :8400008
  • Investigational Site Number :8400004
  • Investigational Site Number :2760001
  • Investigational Site Number :3800001
  • Investigational Site Number :5280001
  • Investigational Site Number :5780001
  • Investigational Site Number :8260001

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BIVV020 IV

Arm Description

Single administration dose 1, plus two optional doses of BIVV020 administered intravenously.

Outcomes

Primary Outcome Measures

Assessment of adverse events (AEs)
Number of participants with adverse events (AEs)

Secondary Outcome Measures

Mean change from baseline in bilirubin over time
Assessment of total bilirubin
Mean change from baseline in hemoglobin over time
Assessment of hemoglobin
Complement System Classical Pathway Levels as Measured by WIESLAB Assay
Inhibition by BIVV020 of the complement system classical pathway measured by the WIESLAB assay
Complement System Alternative Pathway Levels as Measured by WIESLAB Assay
Effect of BIVV0020 on the complement system alternative pathway measured by the WIESLAB assay
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.
Total Complement Factor C4 Levels
Total C4 Levels will be assessed in plasma using complement assays
PK parameter: Cmax
Observed maximum plasma concentration
PK parameter: tmax
Observed first time to reach Cmax
PK parameter: AUClast
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast
PK parameter: AUC0-∞
Calculated area under the plasma concentration versus time curve extrapolated to infinity
Number of participants with anti-BIVV antibodies
Observed number of participants with BIVV020 antibodies

Full Information

First Posted
January 29, 2020
Last Updated
April 25, 2022
Sponsor
Bioverativ, a Sanofi company
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1. Study Identification

Unique Protocol Identification Number
NCT04269551
Brief Title
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

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 15, 2020 (Actual)
Primary Completion Date
January 6, 2022 (Actual)
Study Completion Date
January 6, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bioverativ, a Sanofi company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Haemolytic Anaemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BIVV020 IV
Arm Type
Experimental
Arm Description
Single administration dose 1, plus two optional doses of BIVV020 administered intravenously.
Intervention Type
Drug
Intervention Name(s)
BIVV020
Intervention Description
Pharmaceutical form:solution for injection Route of administration: intravenous
Primary Outcome Measure Information:
Title
Assessment of adverse events (AEs)
Description
Number of participants with adverse events (AEs)
Time Frame
Screening to Day 106
Secondary Outcome Measure Information:
Title
Mean change from baseline in bilirubin over time
Description
Assessment of total bilirubin
Time Frame
Day 1 to Day 106
Title
Mean change from baseline in hemoglobin over time
Description
Assessment of hemoglobin
Time Frame
Day 1 to Day 106
Title
Complement System Classical Pathway Levels as Measured by WIESLAB Assay
Description
Inhibition by BIVV020 of the complement system classical pathway measured by the WIESLAB assay
Time Frame
Day 1 to Day 106
Title
Complement System Alternative Pathway Levels as Measured by WIESLAB Assay
Description
Effect of BIVV0020 on the complement system alternative pathway measured by the WIESLAB assay
Time Frame
Day 1 to Day 106
Title
Total Complement (CH50) Levels
Description
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.
Time Frame
Day 1 to Day 106
Title
Total Complement Factor C4 Levels
Description
Total C4 Levels will be assessed in plasma using complement assays
Time Frame
Day 1 to Day 106
Title
PK parameter: Cmax
Description
Observed maximum plasma concentration
Time Frame
Day 1 to Day 106
Title
PK parameter: tmax
Description
Observed first time to reach Cmax
Time Frame
Day 1 to Day 106
Title
PK parameter: AUClast
Description
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast
Time Frame
Day 1 to Day 106
Title
PK parameter: AUC0-∞
Description
Calculated area under the plasma concentration versus time curve extrapolated to infinity
Time Frame
Day 1 to Day 106
Title
Number of participants with anti-BIVV antibodies
Description
Observed number of participants with BIVV020 antibodies
Time Frame
Day 1 to Day 106

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria : Male and/or female patients, ≥ 18 years of age with cold agglutinin disease as defined by: Chronic hemolysis per Investigator's judgement, Polyspecific direct antiglobulin test (DAT) positive, Monospecific DAT strongly positive for C3d, Cold agglutinin (CAg) titer ≥ 64 at 4 C; and, 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :8400002
City
Fayetteville
State/Province
Georgia
ZIP/Postal Code
30214
Country
United States
Facility Name
Investigational Site Number :8400009
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Investigational Site Number :8400006
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Investigational Site Number :8400008
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Investigational Site Number :8400004
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States
Facility Name
Investigational Site Number :2760001
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Investigational Site Number :3800001
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Investigational Site Number :5280001
City
Amsterdam
ZIP/Postal Code
1105AZ
Country
Netherlands
Facility Name
Investigational Site Number :5780001
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Facility Name
Investigational Site Number :8260001
City
London
State/Province
London, City Of
ZIP/Postal Code
NW1 2PJ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Learn more about this trial

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

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