A Study to Assess the Efficacy and Safety of BIVV009 (Sutimlimab) in Participants With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion (Cardinal Study)

NCT ID: NCT03347396

Last Updated: 2022-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-05
• Study Completion Date: 2021-10-05

Brief Summary

The purpose of Part A was to determine whether sutimlimab administration resulted in a greater than or equal to (>=) 2 grams per deciliter (g/dL) increase in hemoglobin (Hgb) levels or increased Hgb to >= 12 g/dL and obviated the need for blood transfusion during treatment in participants with primary cold agglutinin disease (CAD) who had 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 CAD.

Conditions

Agglutinin Disease, Cold

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BIVV009

Participants with primary CAD who had a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an intravenous (IV) infusion of BIVV009 6.5 grams (g) (if body weight was less than \[\<\] 75 kilograms \[kg\]) or BIVV009 7.5 g (if body weight was 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) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.

Group Type: EXPERIMENTAL

BIVV009

Intervention Type: DRUG

Sutimlimab was administered as intravenous (IV) infusion.

Interventions

BIVV009

Sutimlimab was administered as intravenous (IV) infusion.

Intervention Type: DRUG

Other Intervention Names

Sutimlimab

Eligibility Criteria

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; e) Immunoglobulin G (IgG) DAT less than or equal to (<=) 1+, and f) No overt malignant disease.
• History of at least one documented blood transfusion within 6 months of enrollment.
• 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.
• Clinically relevant infection of any kind within the month preceding enrollment (e.g., 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 adjudicated on a case-by-case basis during the Confirmatory Review of Patient Eligibility.
• Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening.
• Positive human immunodeficiency virus (HIV) antibody at screening.
• Treatment with rituximab monotherapy within 3 months or rituximab combination therapies (e.g., with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bioverativ, a Sanofi company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Arizona Oncology Associates PC

Tucson, Arizona, United States

USC/Keck School of Medicine

Los Angeles, California, United States

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Georgetown University Medical Center

Georgetown, District of Columbia, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Montefiore Medical Center

New York, New York, United States

New York Medical College at Westchester Medical Center

Valhalla, New York, United States

East Carolina University

Greenville, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

UW Hospitals and Clinics

Madison, Wisconsin, United States

USC Health Clinics

Buderim, Queensland, Australia

Ballarat Oncology & Haematology

Ballarat, Victoria, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Medical University of Vienna

Vienna, , Austria

ZNA Stuivenberg

Antwerp, , Belgium

Centre Hospitalier Jolimont

La Louvière, , Belgium

University Hospitals Leuven

Leuven, , Belgium

St. Michael's Hospital

Toronto, Ontario, Canada

McGill University Health Center

Montreal, Quebec, Canada

University of Alberta

Edmonton, , Canada

CHU de Caen

Caen, , France

Centre Hospitalier Henri Mondor

Créteil, , France

Centre Hospitalier Lyon Sud

Lyon, , France

Gemeinschaftspraxis Hämatologie-Onkologie

Dresden, , Germany

Universitätsklinikum Essen

Essen, , Germany

Univ Ulm, Inst Klin. Transfusions. Immungen

Ulm, , Germany

Hadassah Medical Center

Jerusalem, , Israel

Laniado Hospital

Netanya, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

A. O. Spedali Civili di Brescia

Brescia, , Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

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

Rome, , Italy

U.O.C. Ematologia Ospedale San Bortolo

Vicenza, , Italy

Tokai University Hospital

Isehara, Kanagawa, Japan

Saitama Medical University Hospital

Iruma-gun, Saitama, Japan

Juntendo University Nerima Hospital

Tokyo, Tokyo-To, Japan

Academisch Medisch Centrum

Amsterdam, , Netherlands

Haukeland University Hospital

Bergen, , Norway

Oslo University Hospital

Oslo, , Norway

St Olavs Hospital, Avdeling for blodsykdommer

Trondheim, , Norway

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Hospital Clinci i Provincial de Barcelona

Barcelona, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitario Dr. Peset

Valencia, , Spain

St James Hospital, Leeds

Leeds, , United Kingdom

University College London

London, , United Kingdom

Countries

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

References

Alexander Röth, Wilma Barcellini, Shirley D'Sa, Yoshitaka Miyakawa, Catherine M Broome, Marc Michel, David J. Kuter, Bernd Jilma, Tor Henrik Anderson Tvedt, Stella Lin, Xiaoyu Jiang, Caroline Reuter, William Hobbs, Sigbjørn Berentsen; Inhibition of Complement C1s with Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Results from the Phase 3 Cardinal Study. Blood 2019; 134 (Supplement_2): LBA-2. doi: https://doi.org/10.1182/blood-2019-132490

Reference Type: RESULT

Roth A, Broome CM, Barcellini W, Tvedt THA, Miyakawa Y, D'Sa S, Cella D, Bozzi S, Jayawardene D, Yoo R, Shafer F, Wardecki M, Weitz IC. Long-term sutimlimab improves quality of life for patients with cold agglutinin disease: CARDINAL 2-year follow-up. Blood Adv. 2023 Oct 10;7(19):5890-5897. doi: 10.1182/bloodadvances.2022009318.

Reference Type: DERIVED

PMID: 37459203 (View on PubMed)

Roth A, Barcellini W, D'Sa S, Miyakawa Y, Broome CM, Michel M, Kuter DJ, Jilma B, Tvedt THA, Weitz IC, Yoo R, Jayawardene D, Vagge DS, Kralova K, Shafer F, Wardecki M, Lee M, Berentsen S. Sustained inhibition of complement C1s with sutimlimab over 2 years in patients with cold agglutinin disease. Am J Hematol. 2023 Aug;98(8):1246-1253. doi: 10.1002/ajh.26965. Epub 2023 May 29.

Reference Type: DERIVED

PMID: 37246953 (View on PubMed)

Roth A, Barcellini W, Tvedt THA, Miyakawa Y, Kuter DJ, Su J, Jiang X, Hobbs W, Arias JM, Shafer F, Weitz IC. Sutimlimab improves quality of life in patients with cold agglutinin disease: results of patient-reported outcomes from the CARDINAL study. Ann Hematol. 2022 Oct;101(10):2169-2177. doi: 10.1007/s00277-022-04948-y. Epub 2022 Aug 23.

Reference Type: DERIVED

PMID: 35999387 (View on PubMed)

Tvedt THA, Steien E, Ovrebo B, Haaverstad R, Hobbs W, Wardecki M, Tjonnfjord GE, Berentsen SA. Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery. Am J Hematol. 2022 Feb 1;97(2):E51-E54. doi: 10.1002/ajh.26409. Epub 2021 Dec 11. No abstract available.

Reference Type: DERIVED

PMID: 34778998 (View on PubMed)

Roth A, Barcellini W, D'Sa S, Miyakawa Y, Broome CM, Michel M, Kuter DJ, Jilma B, Tvedt THA, Fruebis J, Jiang X, Lin S, Reuter C, Morales-Arias J, Hobbs W, Berentsen S. Sutimlimab in Cold Agglutinin Disease. N Engl J Med. 2021 Apr 8;384(14):1323-1334. doi: 10.1056/NEJMoa2027760.

Reference Type: DERIVED

PMID: 33826820 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BIVV009-03

Identifier Type: OTHER

Identifier Source: secondary_id

2017-003538-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC16215

Identifier Type: -

Identifier Source: org_study_id