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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 (Cadenza Study)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03347422
Recruitment Status : Recruiting
First Posted : November 20, 2017
Last Update Posted : July 29, 2019
Information provided by (Responsible Party):
Bioverativ Therapeutics Inc.

Brief Summary:
The purpose of Part A is to determine whether sutimlimab administration results in a greater than or equal to (>=)1.5 gram 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 is to evaluate the long-term safety and tolerability of sutimlimab in participants with primary CAD.

Condition or disease Intervention/treatment Phase
Agglutinin Disease, Cold Drug: Sutimlimab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Sutimlimab in Patients With Primary Cold Agglutinin Disease Without a Recent History of Blood Transfusion
Actual Study Start Date : November 20, 2017
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Part A: sutimlimab or Placebo
In Part A, participants will be randomized 1:1 to receive an intravenous (IV) infusion of sutimlimab or placebo.
Drug: Sutimlimab
Sutimlimab will be administered by IV.

Drug: Placebo
Placebo will be administered by IV.

Experimental: Part B: Response Extension Phase (sutimlimab)
In Part B, all participants will undergo blinded cross-over loading doses to allow all participants to receive sutimlimab while maintaining Part A blinding.
Drug: Sutimlimab
Sutimlimab will be administered by IV.

Primary Outcome Measures :
  1. Part A: Percentage of Participants With Response (R) [ Time Frame: Up to Week 26 ]
    A participant will be considered a responder if he or she did not receive a blood transfusion from Week 5 through Week 26 (EOT) and did not receive treatment for primary cold agglutinin disease (CAD) beyond what is permitted per protocol. Additionally, the participant's hemoglobin (Hgb) level must meet the following criterion: Hgb increase greater than or equal to (>=) 1.5 gram per deciliter (g/dL) from baseline (defined as the last Hgb value before administration of the first dose of study drug) at treatment assessment endpoint.

  2. Part B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: Approximately 1 year ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Secondary Outcome Measures :
  1. Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level up to Week 26 [ Time Frame: Baseline Up to Week 26 ]
    Mean change from baseline in hemoglobin (Hgb) level up to Week 26 will be assessed.

  2. Part A: Mean Change From Baseline in Bilirubin up to Week 26 [ Time Frame: Baseline up to Week 26 ]
    Mean change from baseline in bilirubin up to Week 26 will be assessed.

  3. Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) [ Time Frame: Baseline up to Week 26 ]
    FACIT-Fatigue scale consists of 13 questions assessed using a 5 point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question are added to obtain a total score. The range of possible scores is 0-52, with higher score indicating more fatigue.

  4. Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) up to Week 26 [ Time Frame: Baseline up to Week 26 ]
    Mean change from baseline in LDH up to Week 26 will be assessed.

  5. Part A: Percentage of Participants With Solicited Symptomatic Anemia at End of Treatment (EOT) [ Time Frame: At EOT (Day 182) ]
    Symptomatic anemia is defined as fatigue, weakness, shortness of breath, palpitations, fast heart beat, light headedness, and/or chest pain.

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Body weight of greater than or equal to (>=) 39 kilogram (kg) at Screening
  • Confirmed diagnosis of primary cold agglutinin disease (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 (IgG) DAT less than or equal to (<=) 1+, and, f) No overt malignant disease
  • Hemoglobin level <= 10.0 gram per deciliter (g/dL)
  • Bilirubin level above the normal reference range, including patients 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 (example, active hepatitis C, pneumonia)
  • Clinical diagnosis of systemic lupus erythematosus (SLE); or other autoimmune disorders with anti-nuclear antibodies at Screening. Anti-nuclear antibodies of long-standing duration without associated clinical symptoms will be 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 (example, with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03347422

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Contact: Bioverativ Therapeutics Inc, Waltham, MA, USA 1-844-308-0808(US only)

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United States, Arizona
Arizona Oncology Associates PC Recruiting
Tucson, Arizona, United States, 85711
Contact: Stacey Kimbell    520-668-5678   
Principal Investigator: Dr. Michael Boxer         
United States, California
USC/Keck School of Medicine Recruiting
Los Angeles, California, United States, 90033
Contact: Christine Duran    323-865-0371   
Principal Investigator: Dr. Ilene Weitz         
The Oncology Institute of Hope and Innovation Withdrawn
Whittier, California, United States, 90603
United States, District of Columbia
Georgetown University Medical Center Recruiting
Georgetown, District of Columbia, United States, 20007
Contact: Kerritt Saintal    713-559-7633   
Principal Investigator: Catherine Broome         
United States, Florida
Cleveland Clinic Florida Recruiting
Weston, Florida, United States, 33331
Contact: Sharon Berbick    954-487-2255   
Principal Investigator: Dr. Chakra Chaulagain         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: David Kuter, MD    617-726-8033   
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jean M Connors, MD    617-525-9337   
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Ashley Simpson    314-286-1550   
Principal Investigator: Dr. Morey Blinder         
United States, New York
Montefiore Medical Center Recruiting
New York, New York, United States, 10461
Contact: Liem Nguyen, Study Coordinator    718-430-2748   
Principal Investigator: Dr. Irina Murakhovskaya         
New York Medical College at Westchester Medical Center Recruiting
Valhalla, New York, United States, 10595
Contact: Judy Ann Moore    914-533-4115   
Principal Investigator: Seah Lim, MD         
United States, North Carolina
East Carolina University Recruiting
Greenville, North Carolina, United States, 27834
Contact: Tiffanie Moore    252-744-1720   
Principal Investigator: Dr. Darla Liles         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Eric Parsons   
Principal Investigator: Bernard Silver, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Mary Kelty   
Principal Investigator: Dr. J. Eric Russell         
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Jordan Driscoll, Research Coordinator    412-246-6009   
Contact: Jude C Jonassaint, Program Manager   
Principal Investigator: Dr. Joseph E. Kiss         
United States, Wisconsin
UW Hospitals and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact    608-262-5223      
Contact    800-622-8922      
Principal Investigator: Dr. Eliot Williams         
Australia, Queensland
USC Health Clinics Recruiting
Buderim, Queensland, Australia, 4556
Contact: USC Clinical Trials Centre (Sunshine Coast Haematology and Oncology Centre)    +61 7 54563797   
Australia, Victoria
Ballarat Oncology & Haematology Recruiting
Ballarat, Victoria, Australia, 3350
Contact: Anne Morcombe    +61 3 5339 8000   
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
Contact: Micheleine Uhe    03 9594 4044   
Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Sarah Ely    +43 1 40 400 29850   
Principal Investigator: Dr Bernd Jilma, MD         
ZNA Stuivenberg Recruiting
Antwerpen, Belgium, 2060
Contact: Caroline De Man    +32 (0)3 217 74 48   
Principal Investigator: Dr Ka Lung WU         
Centre Hospitalier Jolimont Withdrawn
La Louvière, Belgium, 7100
University Hospitals Leuven Recruiting
Leuven, Belgium, 3000
Contact: Jill Pannecoucke    +32 (0)16 34 15 74   
Principal Investigator: Pr Daan Dierickx         
Canada, Ontario
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B1W8
Contact: Aziz Jiwajee    416-864-5354   
Principal Investigator: Dr. Katerina Pavenski         
Canada, Quebec
McGill University Health Center Recruiting
Montréal, Quebec, Canada, H4A3J1
Contact: Sandra Pepin    (514) 934-1934 ext 23737   
Contact: Victoria Nam-Amnath    (514) 934-1934 ext 68205   
Principal Investigator: Dr. Patricia Pelletier         
University of Alberta Withdrawn
Edmonton, Canada, T6G1Z1
CHU d'Angers Recruiting
Angers Cedex 9, France, 49933
Contact: Denous-Chataigner Paul    +33 241 356 727   
Principal Investigator: Dr Corentin Orvain, MD         
Hôpital de Caen Recruiting
Caen, France, 14033
Contact: Mr. Girard Emanuel    +33 (0)2 312 726 79   
Principal Investigator: Dr Cheze         
Centre Hospitalier Henri Mondor Recruiting
Créteil, France, 94000
Contact: Mrs. Laetitia Languille    +33 (0) 1 49 81 40 67   
Principal Investigator: Pr Michel         
Centre Hospitalier Lyon Sud Recruiting
Pierre-Bénite, France, 69495
Contact: Mrs. Cecile Francoise    +33 (0) 4 78 86 43 35   
Principal Investigator: Dr Lazareth,         
Gemeinschaftspraxis Hämatologie-Onkologie Recruiting
Dresden, Germany, 1307
Contact: Antje van der Seylberg    +49 351 44 00022   
Principal Investigator: Dr Thomas Illmer, MD         
Universitätsklinikum Essen Recruiting
Essen, Germany, 45147
Contact: Nicole Preising    +49 201 723 4620   
Principal Investigator: Dr Alexander Roeth, MD         
Univ Ulm, Inst Klin. Transfusions. Immungen Recruiting
Ulm, Germany, 89081
Contact: Marina Pfetsch    +49 731 150 6790   
Principal Investigator: Prof Dr Hubert Schrezenmeier, MD         
Hadassah Medical Center Recruiting
Jerusalem, Israel, 91120
Contact: Ela Shai    +972-5-05172903   
Principal Investigator: Dr Yosef Kalish, MD         
Laniado Hospital Recruiting
Netanya, Israel, 4244916
Contact: Dikla Varsano    +972-9-8925248   
Contact: Aviv Avdi   
Principal Investigator: Dr Shlomo Bulvik, MD         
Tel Aviv Sourasky Medical Center Withdrawn
Tel Aviv, Israel, 64239
A. O. Spedali Civili di Brescia Recruiting
Brescia, Italy, 25123
Contact: Cinzia Lamorgese    +39 030 3996269   
Principal Investigator: Dr Giuseppe Rossi, MD         
Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico Recruiting
Milan, Italy, 20122
Contact: Giulia Milesi    +39 02 55033050   
Principal Investigator: Dr Wilma Barcellini, MD         
U.O.C. Ematologia- Policlinico "A. Gemelli" Recruiting
Rome, Italy, 00168
Contact: Marika Picardi    +39 06 30154180   
Principal Investigator: Dr Luana Fianchi, MD         
U.O.C. Ematologia Ospedale San Bortolo Recruiting
Vicenza, Italy, 36100
Contact: Laura Lissandrini    +39 444 753518   
Principal Investigator: Dr Eros di Bona, MD         
Japanese Red Cross Society Himeji Hospital Recruiting
Himeji, Hyogo, Japan, 670-8540
Ishikawa Prefectural Central Hospital Recruiting
Kanazawa, Ishikawa-ken, Japan, 9208530
Tokai University Hospital Recruiting
Isehara, Kanagawa, Japan, 259-1193
Osaka University Hospital Recruiting
Suita, Osaka, Japan, 565-0871
Saitama Medical University Hospital Recruiting
Iruma-gun, Saitama-Ken, Japan, 350-0495
Aichi Medical University Hospital Recruiting
Nagakute, Japan, 480-1195
Academisch Medisch Centrum Recruiting
Amsterdam, Netherlands, 1105
Contact: Roel Remij    +31(0)20-5665950   
Principal Investigator: Dr. Josephine Vos         
Leids Universitair Medisch Centrum Recruiting
Leiden, Netherlands, 2333
Contact: Willemien Benckhuijsen    +31 7152 651 29   
Principal Investigator: Dr Liesbeth Oosten, MD         
Haukeland University Hospital Recruiting
Bergen, Norway, 5053
Contact: Anita Bøtter Brevik    +4755975362   
Contact: Kristin Eikevåg         
Principal Investigator: Dr Tor Henrik Anderson Tvedt         
Oslo University Hospital Withdrawn
Oslo, Norway, 0372
St Olavs Hospital, Avdeling for blodsykdommer Recruiting
Trondheim, Norway, 7030
Contact: Turid Neverdal Almvik    +4772925041   
Principal Investigator: Dr Henrik Hjort Hansen         
Hospital Universitario Puerta de Hierro Recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Isabel Salcedo    +34 911 916 481   
Principal Investigator: Dr Jose Luis Bueno, MD         
Hospital Clinci i Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Principal Investigator: Dr Joan Cid, +34 932 275 448         
Hospital Universitario Virgen del Rocio Recruiting
Sevilla, Spain, 41013
Contact: Rocio Roncel    +34 955 013 277   
Principal Investigator: Dr Jesus Martin Sanchez, MD         
Hospital Universitario Dr. Peset Recruiting
Valencia, Spain, 46017
Contact: David Ivars    +34 961 622 536   
Principal Investigator: Dr Miguel Fernandez Zarzoso, MD         
United Kingdom
St James Hospital, Leeds Recruiting
Leeds, United Kingdom, LS9 7TF
Contact: Lauran Tindall    +44113 2068561   
Imperial College Healthcare NHS Trust, Hammersmith Hospital Recruiting
London, United Kingdom, W12 0HS
Contact: Simona Deplano   
Contact: Camelia Vladescu    020 331 34306   
University College London Recruiting
London, United Kingdom, WC1E 6AG
Contact: Kike Ibikunle    +4420 3447 7101   
Sponsors and Collaborators
Bioverativ Therapeutics Inc.

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Responsible Party: Bioverativ Therapeutics Inc. Identifier: NCT03347422     History of Changes
Other Study ID Numbers: BIVV009-04
2017-003539-12 ( EudraCT Number )
BIVV009-04 ( Other Identifier: Bioverativ Therapeutics Inc. )
First Posted: November 20, 2017    Key Record Dates
Last Update Posted: July 29, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Hemolytic, Autoimmune
Anemia, Hemolytic
Hematologic Diseases
Autoimmune Diseases
Immune System Diseases
Cold agglutinins
Immunologic Factors
Physiological Effects of Drugs