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

• ClinicalTrials.gov Identifier: NCT04269551
• Recruitment Status: Completed
• First Posted: February 17, 2020
• Last Update Posted: May 2, 2022
• Sponsor: Bioverativ, a Sanofi company
• Information provided by (Responsible Party): Sanofi ( Bioverativ, a Sanofi company )

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

Condition or disease	Intervention/treatment	Phase
Autoimmune Haemolytic Anaemia	Drug: BIVV020	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 15, 2020
• Actual Primary Completion Date: January 6, 2022
• Actual Study Completion Date: January 6, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Assessment of adverse events (AEs) [ Time Frame: Screening to Day 106 ]
   Number of participants with adverse events (AEs)

Secondary Outcome Measures :

1. Mean change from baseline in bilirubin over time [ Time Frame: Day 1 to Day 106 ]
   Assessment of total bilirubin
2. Mean change from baseline in hemoglobin over time [ Time Frame: Day 1 to Day 106 ]
   Assessment of hemoglobin
3. Complement System Classical Pathway Levels as Measured by WIESLAB Assay [ Time Frame: Day 1 to Day 106 ]
   Inhibition by BIVV020 of the complement system classical pathway measured by the WIESLAB assay
4. Complement System Alternative Pathway Levels as Measured by WIESLAB Assay [ Time Frame: Day 1 to Day 106 ]
   Effect of BIVV0020 on the complement system alternative pathway measured by the WIESLAB assay
5. Total Complement (CH50) Levels [ Time Frame: 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.
6. Total Complement Factor C4 Levels [ Time Frame: Day 1 to Day 106 ]
   Total C4 Levels will be assessed in plasma using complement assays
7. PK parameter: Cmax [ Time Frame: Day 1 to Day 106 ]
   Observed maximum plasma concentration
8. PK parameter: tmax [ Time Frame: Day 1 to Day 106 ]
   Observed first time to reach Cmax
9. PK parameter: AUClast [ Time Frame: 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
10. PK parameter: AUC0-∞ [ Time Frame: Day 1 to Day 106 ]
    Calculated area under the plasma concentration versus time curve extrapolated to infinity
11. Number of participants with anti-BIVV antibodies [ Time Frame: Day 1 to Day 106 ]
    Observed number of participants with BIVV020 antibodies

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Georgia

Investigational Site Number :8400002

Fayetteville, Georgia, United States, 30214

United States, Missouri

Investigational Site Number :8400009

Saint Louis, Missouri, United States, 63110

United States, New York

Investigational Site Number :8400006

Bronx, New York, United States, 10467

United States, Pennsylvania

Investigational Site Number :8400008

Pittsburgh, Pennsylvania, United States, 15232

United States, Washington

Investigational Site Number :8400004

Seattle, Washington, United States, 98108

Germany

Investigational Site Number :2760001

Essen, Germany, 45147

Italy

Investigational Site Number :3800001

Milano, Italy, 20122

Netherlands

Investigational Site Number :5280001

Amsterdam, Netherlands, 1105AZ

Norway

Investigational Site Number :5780001

Bergen, Norway, 5021

United Kingdom

Investigational Site Number :8260001

London, London, City Of, United Kingdom, NW1 2PJ

Sponsors and Collaborators

Bioverativ, a Sanofi company

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Bioverativ, a Sanofi company
• ClinicalTrials.gov Identifier: NCT04269551
• Other Study ID Numbers: PDY16370; 2019-001844-22 ( EudraCT Number ); U1111-1233-0831 ( Other Identifier: UTN )
• First Posted: February 17, 2020
• Last Update Posted: May 2, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Anemia, Hemolytic, Autoimmune; Anemia, Hemolytic; Anemia; Hematologic Diseases; Autoimmune Diseases; Immune System Diseases