A Study to Assess the Efficacy and Safety of BIVV009 (Sutimlimab) in Participants With Primary Cold Agglutinin Disease Without A Recent History of Blood Transfusion

NCT ID: NCT03347422

Last Updated: 2022-12-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-17

Study Completion Date

2021-12-03

Brief Summary

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The purpose of Part A was to determine whether sutimlimab administration resulted in a greater than or equal to (\>=)1.5 grams per deciliter (g/dL) increase in hemoglobin (Hgb) level and avoidance of transfusion in participants with primary cold agglutinin disease (CAD) without a recent history of blood transfusion. The purpose of Part B was to evaluate the long-term safety and tolerability of sutimlimab in participants with primary CAD.

Detailed Description

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The planned total study duration per participant was approximately 1.5 to 2.5 years.

Conditions

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Cold Agglutinin Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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BIVV009/BIVV009

Participants with primary CAD and without a recent history of blood transfusion during the last 6 months prior to enrollment in this study, received an intravenous (IV) infusion of BIVV009 6.5 g (for participants less than \[\<\]75 kilograms \[kg\]) or 7.5 g dose (for participants greater than or equal to \[\>=\]75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26), received placebo on Week 26 and continued to receive BIVV009 6.5 or 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks (for 6.5 g) or 121 weeks (for 7.5 g). All participants who completed Part A elected to continue in Part B.

Group Type EXPERIMENTAL

sutimlimab (BIVV009)

Intervention Type DRUG

Pharmaceutical form: solution for injection Route of administration: intravenous (i.v.)

Placebo/BIVV009

Participants with primary CAD and without a recent history of blood transfusion during the last 6 months prior to enrollment in this study, received an IV infusion of placebo matched to BIVV009 on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) received BIVV009 6.5 (if \<75 kg) or 7.5 g (if \>=75 kg) in Part B, on Week 26 and Week 27 and every 2 weeks thereafter for up to an additional 123 weeks (for 6.5 g) or 137 weeks (for 7.5 g). All participants who completed Part A elected to continue in Part B.

Group Type EXPERIMENTAL

sutimlimab (BIVV009)

Intervention Type DRUG

Pharmaceutical form: solution for injection Route of administration: intravenous (i.v.)

placebo

Intervention Type DRUG

Pharmaceutical form: solution for injection Route of administration: intravenous (i.v.)

Interventions

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sutimlimab (BIVV009)

Pharmaceutical form: solution for injection Route of administration: intravenous (i.v.)

Intervention Type DRUG

placebo

Pharmaceutical form: solution for injection Route of administration: intravenous (i.v.)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Body weight of \>=39 kg at screening.
* Confirmed diagnosis of primary CAD based on the following criteria: a) Chronic hemolysis, b) Polyspecific direct antiglobulin test (DAT) positive, c) Monospecific DAT strongly positive for C3d, d) Cold agglutinin titer \>= 64 at 4 degree Celsius, and e) Immunoglobulin G DAT less than or equal to (\<=) 1+, and, f) No overt malignant disease.
* Hemoglobin level \<= 10.0 g/dL.
* Bilirubin level above the normal reference range, including participants with Gilbert's Syndrome.

Exclusion Criteria

* Cold agglutinin syndrome secondary to infection, rheumatologic disease, or active hematologic malignancy.
* History of blood transfusion within 6 months of screening, or history of more than one blood transfusion within 12 months of screening.
* Clinically relevant infection of any kind within the month preceding enrollment (example, active hepatitis C, pneumonia).
* Clinical diagnosis of systemic lupus erythematosus; or other autoimmune disorders with anti-nuclear antibodies at screening. Anti-nuclear antibodies of long-standing duration without associated clinical symptoms would be adjudicated on a case-by-case basis during the confirmatory review of participant eligibility.
* Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at screening.
* Positive human immunodeficiency virus antibody at screening.
* Treatment with rituximab monotherapy within 3 months or rituximab combination therapies (example, with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bioverativ, a Sanofi company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Arizona Oncology Associates PC

Tucson, Arizona, United States

Site Status

USC/Keck School of Medicine

Los Angeles, California, United States

Site Status

Georgetown University Medical Center

Georgetown, District of Columbia, United States

Site Status

Cleveland Clinic Florida

Weston, Florida, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Montefiore Medical Center

New York, New York, United States

Site Status

New York Medical College at Westchester Medical Center

Valhalla, New York, United States

Site Status

East Carolina University

Greenville, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

UW Hospitals and Clinics

Madison, Wisconsin, United States

Site Status

USC Health Clinics

Buderim, Queensland, Australia

Site Status

Ballarat Oncology & Haematology

Ballarat, Victoria, Australia

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

Perth Blood Institute

West Perth, Western Australia, Australia

Site Status

Medical University of Vienna

Vienna, , Austria

Site Status

ZNA Stuivenberg

Antwerp, , Belgium

Site Status

University Hospitals Leuven

Leuven, , Belgium

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

McGill University Health Center

Montreal, Quebec, Canada

Site Status

CHU d'Angers

Angers, , France

Site Status

Hôpital de Caen

Caen, , France

Site Status

Centre Hospitalier Henri Mondor

Créteil, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Gemeinschaftspraxis Hämatologie-Onkologie

Dresden, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

Univ Ulm, Inst Klin. Transfusions. Immungen

Ulm, , Germany

Site Status

Hadassah Medical Center

Jerusalem, , Israel

Site Status

Laniado Hospital

Netanya, , Israel

Site Status

A. O. Spedali Civili di Brescia

Brescia, , Italy

Site Status

Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

U.O.C. Ematologia- Policlinico "A. Gemelli"

Rome, , Italy

Site Status

U.O.C. Ematologia Ospedale San Bortolo

Vicenza, , Italy

Site Status

Japanese Red Cross Society Himeji Hospital

Himeji, Hyōgo, Japan

Site Status

Ishikawa Prefectural Central Hospital

Kanazawa, Ishikawa-ken, Japan

Site Status

Tokai University Hospital

Isehara, Kanagawa, Japan

Site Status

Osaka University Hospital

Suita, Osaka, Japan

Site Status

Saitama Medical University Hospital

Iruma-gun, Saitama, Japan

Site Status

Aichi Medical University Hospital

Nagakute, , Japan

Site Status

Academisch Medisch Centrum

Amsterdam, , Netherlands

Site Status

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Site Status

Haukeland University Hospital

Bergen, , Norway

Site Status

St Olavs Hospital, Avdeling for blodsykdommer

Trondheim, , Norway

Site Status

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Site Status

Hospital Clinci i Provincial de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitario Dr. Peset

Valencia, , Spain

Site Status

St James Hospital, Leeds

Leeds, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust, Hammersmith Hospital

London, , United Kingdom

Site Status

University College London

London, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada France Germany Israel Italy Japan Netherlands Norway Spain United Kingdom

References

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Roth A, Broome CM, Barcellini W, Jilma B, Hill QA, Cella D, Tvedt THA, Yamaguchi M, Lee M, Shafer F, Wardecki M, Jiang X, Patel P, Joly F, Weitz IC. Sutimlimab provides clinically meaningful improvements in patient-reported outcomes in patients with cold agglutinin disease: Results from the randomised, placebo-controlled, Phase 3 CADENZA study. Eur J Haematol. 2023 Mar;110(3):280-288. doi: 10.1111/ejh.13903. Epub 2022 Dec 9.

Reference Type DERIVED
PMID: 36403132 (View on PubMed)

Roth A, Berentsen S, Barcellini W, D'Sa S, Jilma B, Michel M, Weitz IC, Yamaguchi M, Nishimura JI, Vos JMI, Storek M, Wong N, Patel P, Jiang X, Vagge DS, Wardecki M, Shafer F, Lee M, Broome CM. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial. Blood. 2022 Sep 1;140(9):980-991. doi: 10.1182/blood.2021014955.

Reference Type DERIVED
PMID: 35687757 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-003539-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BIVV009-04

Identifier Type: OTHER

Identifier Source: secondary_id

EFC16216

Identifier Type: -

Identifier Source: org_study_id