Clinical trial NCT03347422: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cold Agglutinin Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-11-20
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Percentage of Participants With Response to Treatment
timeFrame: From Week 5 through Week 26
measure: Part B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: 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:
measure: Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint
timeFrame: Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
measure: Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at the Treatment Assessment Timepoint
timeFrame: Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
measure: Part A: Mean Change From Baseline in Total Bilirubin Levels at the Treatment Assessment Timepoint
timeFrame: Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
measure: Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint
timeFrame: Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
measure: Part A: Percentage of Participants With Solicited Symptomatic Anemia at Week 26
timeFrame: Week 26
measure: Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points
timeFrame: Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
measure: Part B: Change From Baseline in Total Bilirubin Levels at Each Specified Time Points
timeFrame: Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
measure: Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Each Specified Time Points
timeFrame: Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
measure: Part B: Change From Baseline in 12-Item Short-Form Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Each Specified Time Points
timeFrame: Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
measure: Part B: Change From Baseline in 5-level European Quality of Life 5- Dimensions 5-Level Questionnaire (EQ-5D-5L) Health State Utility Index and VAS Scores at Each Specified Time Points
timeFrame: Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
measure: Part B: Number of Participants With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Each Specified Time Points
timeFrame: Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
measure: Part B: Number of Participants With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Each Specified Time Points
timeFrame: Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
measure: Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points
timeFrame: Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
measure: Part B: Number of Blood Transfusions Per Participant
timeFrame: From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
measure: Part B: Mean Change From Baseline in Haptoglobin Values at Each Specified Time Points
timeFrame: Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
measure: Part B: Number of Healthcare Visits by Type
timeFrame: From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates PC
state: Arizona
city: Los Angeles
country: United States
facility: USC/Keck School of Medicine
state: California
city: Georgetown
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College at Westchester Medical Center
state: New York
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Madison
country: United States
facility: UW Hospitals and Clinics
state: Wisconsin
city: Buderim
country: Australia
facility: USC Health Clinics
state: Queensland
city: Ballarat
country: Australia
facility: Ballarat Oncology & Haematology
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: West Perth
country: Australia
facility: Perth Blood Institute
state: Western Australia
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Angers Cedex 9
country: France
facility: CHU d'Angers
city: Caen
country: France
facility: Hôpital de Caen
city: Créteil
country: France
facility: Centre Hospitalier Henri Mondor
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Dresden
country: Germany
facility: Gemeinschaftspraxis Hämatologie-Onkologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Ulm
country: Germany
facility: Univ Ulm, Inst Klin. Transfusions. Immungen
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Netanya
country: Israel
facility: Laniado Hospital
city: Brescia
country: Italy
facility: A. O. Spedali Civili di Brescia
city: Milan
country: Italy
facility: Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
city: Rome
country: Italy
facility: U.O.C. Ematologia- Policlinico "A. Gemelli"
city: Vicenza
country: Italy
facility: U.O.C. Ematologia Ospedale San Bortolo
city: Himeji
country: Japan
facility: Japanese Red Cross Society Himeji Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: Ishikawa Prefectural Central Hospital
state: Ishikawa-ken
city: Isehara
country: Japan
facility: Tokai University Hospital
state: Kanagawa
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
state: Saitama-Ken
city: Nagakute
country: Japan
facility: Aichi Medical University Hospital
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Trondheim
country: Norway
facility: St Olavs Hospital, Avdeling for blodsykdommer
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Clinci i Provincial de Barcelona
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Leeds
country: United Kingdom
facility: St James Hospital, Leeds
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust, Hammersmith Hospital
city: London
country: United Kingdom
facility: University College London
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.