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)

Bioverativ

Status and phase: Completed; Phase 3

Conditions: Cold Agglutinin Disease

Treatments: Drug: sutimlimab (BIVV009); Drug: placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03347422

2017-003539-12 (EudraCT Number)

BIVV009-04 (Other Identifier)

EFC16216

Details and patient eligibility

About

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.

Full description

The planned total study duration per participant was approximately 1.5 to 2.5 years.

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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42 participants in 2 patient groups

BIVV009/BIVV009

Experimental group

Description:

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.

Treatment:

Drug: sutimlimab (BIVV009)

Placebo/BIVV009

Experimental group

Description:

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.

Treatment:

Drug: placebo

Drug: sutimlimab (BIVV009)