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

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

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

Study Overview

• Status: Completed
• Conditions: Autoimmune Haemolytic Anaemia
• Intervention / Treatment: Drug: BIVV020

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 45147
    • Investigational Site Number :2760001
• Italy
  • Milano, Italy, 20122
    • Investigational Site Number :3800001
• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Investigational Site Number :5280001
• Norway
  • Bergen, Norway, 5021
    • Investigational Site Number :5780001
• United Kingdom
  • London, City Of
    • London, London, City Of, United Kingdom, NW1 2PJ
      • Investigational Site Number :8260001
• United States
  • Georgia
    • Fayetteville, Georgia, United States, 30214
      • Investigational Site Number :8400002
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Investigational Site Number :8400009
  • New York
    • Bronx, New York, United States, 10467
      • Investigational Site Number :8400006
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Investigational Site Number :8400008
  • Washington
    • Seattle, Washington, United States, 98108
      • Investigational Site Number :8400004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIVV020 IV; Single administration dose 1, plus two optional doses of BIVV020 administered intravenously.	Drug: BIVV020; Pharmaceutical form:solution for injection Route of administration: intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of adverse events (AEs)	Number of participants with adverse events (AEs)	Screening to Day 106

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in bilirubin over time	Assessment of total bilirubin	Day 1 to Day 106
Mean change from baseline in hemoglobin over time	Assessment of hemoglobin	Day 1 to Day 106
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
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
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
Total Complement Factor C4 Levels	Total C4 Levels will be assessed in plasma using complement assays	Day 1 to Day 106
PK parameter: Cmax	Observed maximum plasma concentration	Day 1 to Day 106
PK parameter: tmax	Observed first time to reach Cmax	Day 1 to Day 106
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
PK parameter: AUC0-∞	Calculated area under the plasma concentration versus time curve extrapolated to infinity	Day 1 to Day 106
Number of participants with anti-BIVV antibodies	Observed number of participants with BIVV020 antibodies	Day 1 to Day 106

Collaborators and Investigators

• Sponsor: Bioverativ, a Sanofi company

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Actual): January 6, 2022
• Study Completion (Actual): January 6, 2022

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: PDY16370; 2019-001844-22 (EudraCT Number); U1111-1233-0831 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No