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

NCT03347422 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC162162017-003539-12BIVV009-04
• Study Type: interventional
• Target: 42
• Locations: 13 countries
• Sites: 52

Brief Summary

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.

Conditions

Cold Agglutinin Disease

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 blood transfusion from Week 5 through Week 26 (end of treatment) and did not receive treatment for CAD beyond what was permitted per protocol. Additionally, participant's hemoglobin (Hgb) level must have increased to \>=1.5 grams per deciliter (g/dL) from baseline (defined as last Hgb value before administration of first dose of study drug) at treatment assessment timepoint (defined as average of values from the Week 23, 25, and 26 visits). Percentage of responders was calculated together with 95% exact Clopper-Pearson confidence interval (CI).

  From Week 5 through Week 26

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

  Adverse Event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Treatment emergent serious adverse events (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 congenital anomaly/birth defect, was medically important event. Treatment emergent adverse events (TEAEs): AEs that developed, worsened or became serious during the treatment-emergent (TE) period (from first investigational medicinal product \[IMP\] administration in Part B to last IMP administration + 9 weeks follow-up period).

  Part B, 6.5 g cohort: From first dose (Week 26) up to 149 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 184); Part B, 7.5 g cohort: From first dose (Week 26) up to 137 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 172)

Secondary Outcomes (16)

• Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint

  Baseline (Week 0), 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 at the Treatment Assessment Timepoint

  Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

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

  Baseline (Week 0), 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 (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

• Part A: Percentage of Participants With Solicited Symptomatic Anemia at Week 26

  Week 26

Study Arms (2)

BIVV009/BIVV009

EXPERIMENTAL

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.

Drug: sutimlimab (BIVV009)

Placebo/BIVV009

EXPERIMENTAL

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.

Drug: sutimlimab (BIVV009); Drug: placebo

Interventions

sutimlimab (BIVV009) DRUG

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

BIVV009/BIVV009; Placebo/BIVV009

placebo DRUG

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

Placebo/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, 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bioverativ, a Sanofi company: lead

Study Sites (53)

Arizona Oncology Associates PC

Tucson, Arizona, 85711, United States

Location

USC/Keck School of Medicine

Los Angeles, California, 90033, United States

Location

Georgetown University Medical Center

Georgetown, District of Columbia, 20007, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, 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

Perth Blood Institute

West Perth, Western Australia, 6005, Australia

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

ZNA Stuivenberg

Antwerp, 2060, 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

CHU d'Angers

Angers, 49933, France

Location

Hôpital de Caen

Caen, 14033, France

Location

Centre Hospitalier Henri Mondor

Créteil, 94000, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 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

A. O. Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Fondazione IRCSS 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

Japanese Red Cross Society Himeji Hospital

Himeji, Hyōgo, 670-8540, Japan

Location

Ishikawa Prefectural Central Hospital

Kanazawa, Ishikawa-ken, 9208530, Japan

Location

Tokai University Hospital

Isehara, Kanagawa, 259-1193, Japan

Location

Osaka University Hospital

Suita, Osaka, 565-0871, Japan

Location

Saitama Medical University Hospital

Iruma-gun, Saitama, 350-0495, Japan

Location

Aichi Medical University Hospital

Nagakute, 480-1195, Japan

Location

Academisch Medisch Centrum

Amsterdam, 1105, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, 2333, Netherlands

Location

Haukeland University Hospital

Bergen, 5053, 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

Imperial College Healthcare NHS Trust, Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

University College London

London, WC1E 6AG, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 36403132 DERIVED

• 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.

  PMID: 35687757 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: Sanofi

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2017
• First Posted: November 20, 2017
• Study Start: March 17, 2018
• Primary Completion: December 3, 2021
• Study Completion: December 3, 2021
• Last Updated: December 23, 2022
• Results First Posted: December 23, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share

Locations

IL (2); AU (4); CA (2); FR (4); IT (4); NL (2); DE (3); US (14); NO (2); JP (6); BE (2); ES (4); GB (3)