A Study to Assess the Efficacy and Safety of BIVV009 in Participants With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion (Cardinal 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: NCT03347396
Recruitment Status : Recruiting
First Posted : November 20, 2017
Last Update Posted : April 23, 2018
Information provided by (Responsible Party):
Bioverativ Therapeutics Inc.

Brief Summary:
The purpose of Part A is to determine whether BIVV009 administration results in a greater than or equal to (>=) 2 gram per deciliter (g/dL) increase in hemoglobin (Hgb) levels or increases Hgb to >= 12 g/dL and obviates the need for blood transfusion during treatment in participants with primary cold agglutinin disease (CAgD) who have a recent history of blood transfusion.The purpose of Part B is to evaluate the long-term safety and tolerability of BIVV009 in participants with CAgD.

Condition or disease Intervention/treatment Phase
Agglutinin Disease, Cold Drug: BIVV009 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pivotal, Open-label, Multicenter Study to Assess the Efficacy and Safety of BIVV009 in Patients With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion
Actual Study Start Date : November 20, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: BIVV009
Participants will receive an intravenous (IV) infusion of BIVV009. Participants who complete Part A per protocol through the end of treatment visit (Day 182) will participate in Part B, and continue to receive BIVV009 up to 1 year after last patient out (LPO) in Part A.
Drug: BIVV009
BIVV009 will be administered as IV infusion.

Primary Outcome Measures :
  1. Part A: Percentage of Participants With Response (R) [ Time Frame: Up to Week 26 ]
    A participant who meets all of the following criteria will be considered a responder: who did not receive a blood transfusion from Week 5 through Week 26 (end of treatment) and did not receive treatment for cold agglutinin disease (CAgD) beyond what is permitted per protocol. Additionally the participant's hemoglobin (Hgb) level must meet either of the following criteria: Hgb level greater than or equal to (>=) 12 gram per deciliter (g/dL) at the treatment assessment endpoint, 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.

  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 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.

  2. 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.

  3. 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.

  4. Part A: Number of Blood Transfusions After the First 5 Weeks of Study Drug Administration [ Time Frame: 5 Weeks ]
    Number of transfusions after the first 5 weeks of study drug administration will be assessed.

  5. Part A: Number of Blood Units Transfused After the First 5 Weeks of Study Drug Administration [ Time Frame: 5 Weeks ]
    Number of blood units transfused after the first 5 weeks of study drug administration will be assessed.

  6. 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 Hgb level up to Week 26 will be assessed.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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 (CAgD) 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 gram per deciliter (g/dL)
  • Bilirubin level above the normal reference range

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 (eg, active hepatitis C, pneumonia)
  • Clinical diagnosis of systemic lupus erythematosus (SLE); or other autoimmune disorders with anti-nuclear antibodies at Screening
  • 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 (eg, 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): NCT03347396

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

United States, California
The Oncology Institute of Hope and Innovation Recruiting
Whittier, California, United States, 90603
Contact: Kirsten Bettino, Study Coordinator    1 562-693-4477   
Principal Investigator: Dr. Richy Agajanian         
United States, District of Columbia
Georgetown University Medical Center Recruiting
Georgetown, District of Columbia, United States, 20007
Contact: Bradford Simmons, Study Coordinator    1 202-687-0116   
Principal Investigator: Dr. Catherine Broome         
United States, New York
Montefiore Medical Center Recruiting
New York, New York, United States, 10461
Contact: Kelsey Branch, Study Coordinator    718-430-2748   
Contact: Elena Crouch, Study Coordinator   
Principal Investigator: Dr. Irina Murakhovskaya         
New York Medical College at Westchester Medical Center Recruiting
Valhalla, New York, United States, 10595
Contact: Saleha Batool    914-493-3045   
Principal Investigator: Robert G. Lerner, MD         
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Sarah Ely    +43 1 40 400 29850   
Principal Investigator: Dr Bernd Jilma, MD         
Centre Hospitalier Jolimont Recruiting
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,         
University of Alberta Recruiting
Edmonton, Canada, T6G1Z1
Contact: Adult Hematology Research    780-407-6090      
Principal Investigator: Dr. A. Peters, 780-407-1584 ext. 5         
CHU 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: Laetitia Languille    +33 (0) 1 49 81 40 67   
Principal Investigator: Pr Michel,         
Centre Hospitalier Lyon Sud Recruiting
Lyon, France, 69495
Contact: 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         
Laniado Hospital Recruiting
Netanya, Israel, 4244916
Contact: Dikla Varsano   
Contact: Aviv Avdi    +972-9-8925248   
Principal Investigator: Dr Shlomo Bulvik, MD         
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Recruiting
Milan, Italy, 20122
Contact: Giulia Milesi    +39 02 55033050   
Principal Investigator: Dr Wilma Barcellini, MD         
Haukeland University Hospital Recruiting
Bergen, Norway, 5053
Contact: Anita Bøtter Brevik    +4755975362   
Contact: Kristin Eikevåg         
Principal Investigator: Dr Tor Henrik Anderson Tvedt         
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 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         
Sponsors and Collaborators
Bioverativ Therapeutics Inc.

Responsible Party: Bioverativ Therapeutics Inc. Identifier: NCT03347396     History of Changes
Other Study ID Numbers: BIVV009-03
BIVV009-03 ( Other Identifier: Bioverativ Therapeutics Inc. )
2017-003538-10 ( EudraCT Number )
First Posted: November 20, 2017    Key Record Dates
Last Update Posted: April 23, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Anemia, Hemolytic, Autoimmune
Anemia, Hemolytic
Hematologic Diseases
Autoimmune Diseases
Immune System Diseases
Cold agglutinins
Immunologic Factors
Physiological Effects of Drugs