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)

NCT03347396 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC16215BIVV009-032017-003538-10
• Study Type: interventional
• Target: 24
• Locations: 13 countries
• Sites: 48

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

Outcome Measures

Primary Outcomes (2)

• Part A: Percentage of Participants With Response to Treatment

  A participant was considered a responder: if he or she did not receive a blood transfusion from Week 5 through Week 26 (end of treatment in Part A) and did not receive treatment for CAD beyond what was permitted per protocol. Additionally, the participant's hemoglobin (Hgb) level must meet either of the following criteria: Hgb level \>= 12 grams per deciliter (g/dL) at the treatment assessment endpoint (defined as the average of the values from the Week 23, 25, and 26 visits), or Hgb increased \>= 2 g/dL from baseline (defined as the last Hgb value before administration of the first dose of study drug) at treatment assessment endpoint. Percentage of responders was calculated together with a 95% exact Clopper-Pearson confidence interval (CI).

  From Week 5 through Week 26

• Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  An Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TESAEs was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the treatment-emergent (TE) period (from the first investigational medicinal product \[IMP\] administration in Part B to the last IMP administration + 9 weeks follow up period).

  Part B, 6.5 g cohort: From first dose (Week 27) up to 143 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 179); Part B, 7.5 g cohort: From first dose (Week 27) up to 149 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 185)

Secondary Outcomes (18)

• Part A: Mean Change From Baseline in Bilirubin Levels at the Treatment Assessment Timepoint

  Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

• Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Treatment Assessment Timepoint

  Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

• Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint

  Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

• Part A: Number of Blood Transfusions Per Participant

  From Week 5 up to Week 26

• Part A: Number of Blood Units Transfused Per Participant

  From Week 5 up to Week 26

Study Arms (1)

BIVV009

EXPERIMENTAL

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.

Drug: BIVV009

Interventions

BIVV009 DRUG

Sutimlimab was administered as intravenous (IV) infusion.

Also known as: Sutimlimab

BIVV009

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bioverativ, a Sanofi company: lead

Study Sites (49)

Arizona Oncology Associates PC

Tucson, Arizona, 85711, United States

Location

USC/Keck School of Medicine

Los Angeles, California, 90033, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

Georgetown University Medical Center

Georgetown, District of Columbia, 20007, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Montefiore Medical Center

New York, New York, 10461, United States

Location

New York Medical College at Westchester Medical Center

Valhalla, New York, 10595, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UW Hospitals and Clinics

Madison, Wisconsin, 53792, United States

Location

USC Health Clinics

Buderim, Queensland, 4556, Australia

Location

Ballarat Oncology & Haematology

Ballarat, Victoria, 3350, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

Centre Hospitalier Jolimont

La Louvière, 7100, Belgium

Location

University Hospitals Leuven

Leuven, 3000, Belgium

Location

St. Michael's Hospital

Toronto, Ontario, M5B1W8, Canada

Location

McGill University Health Center

Montreal, Quebec, H4A3J1, Canada

Location

University of Alberta

Edmonton, T6G1Z1, Canada

Location

CHU de Caen

Caen, 14033, France

Location

Centre Hospitalier Henri Mondor

Créteil, 94000, France

Location

Centre Hospitalier Lyon Sud

Lyon, 69495, France

Location

Gemeinschaftspraxis Hämatologie-Onkologie

Dresden, 1307, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Univ Ulm, Inst Klin. Transfusions. Immungen

Ulm, 89081, Germany

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Laniado Hospital

Netanya, 4244916, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

A. O. Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

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

Rome, 00168, Italy

Location

U.O.C. Ematologia Ospedale San Bortolo

Vicenza, 36100, Italy

Location

Tokai University Hospital

Isehara, Kanagawa, 259-1193, Japan

Location

Saitama Medical University Hospital

Iruma-gun, Saitama, 350-0495, Japan

Location

Juntendo University Nerima Hospital

Tokyo, Tokyo-To, 177-8521, Japan

Location

Academisch Medisch Centrum

Amsterdam, 1105, Netherlands

Location

Haukeland University Hospital

Bergen, 5053, Norway

Location

Oslo University Hospital

Oslo, 0372, Norway

Location

St Olavs Hospital, Avdeling for blodsykdommer

Trondheim, 7030, Norway

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital Clinci i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

St James Hospital, Leeds

Leeds, LS9 7TF, United Kingdom

Location

University College London

London, WC1E 6AG, United Kingdom

Location

Related Publications (6)

• 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

  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.

  PMID: 37459203 DERIVED

• 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.

  PMID: 37246953 DERIVED

• 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.

  PMID: 35999387 DERIVED

• 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.

  PMID: 34778998 DERIVED

• 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.

  PMID: 33826820 DERIVED

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune

Interventions

sutimlimab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Bioverativ, a Sanofi company

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2017
• First Posted: November 20, 2017
• Study Start: March 5, 2018
• Primary Completion: October 5, 2021
• Study Completion: October 5, 2021
• Last Updated: October 31, 2022
• Results First Posted: October 31, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); IT (4); IL (3); DE (3); FR (3); JP (3); NL (1); US (13); NO (3); BE (3); ES (4); GB (2); CA (3)