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)

• ClinicalTrials.gov Identifier: NCT03347396
• Recruitment Status: Active, not recruiting
• First Posted: November 20, 2017
• Last Update Posted: November 28, 2019
• Sponsor: Bioverativ Therapeutics Inc.
• Information provided by (Responsible Party): Bioverativ Therapeutics Inc.

Study Description

Brief Summary:

The purpose of Part A is to determine whether sutimlimab 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 (CAD) who have 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 CAD.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Pivotal, Open-label, Multicenter Study to Assess the Efficacy and Safety of Sutimlimab 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: September 2020
• Estimated Study Completion Date: September 2020

Arms and Interventions

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

Outcome Measures

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 (CAD) 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.

Eligibility Criteria

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

Criteria

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; 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, 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 (eg, 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 (eg, with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment

Contacts and Locations

  Show 49 Study Locations

Sponsors and Collaborators

Bioverativ Therapeutics Inc.

More Information

• Responsible Party: Bioverativ Therapeutics Inc.
• ClinicalTrials.gov 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
• Last Update Posted: November 28, 2019
• Last Verified: November 2019

• 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; Anemia; Hematologic Diseases; Autoimmune Diseases; Immune System Diseases; Agglutinins; Cold agglutinins; Immunologic Factors; Physiological Effects of Drugs; Hemagglutinins