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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)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03347422
Recruitment Status : Active, not recruiting
First Posted : November 20, 2017
Last Update Posted : September 3, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Bioverativ, a Sanofi company )

Tracking Information
First Submitted Date  ICMJE November 16, 2017
First Posted Date  ICMJE November 20, 2017
Last Update Posted Date September 3, 2020
Actual Study Start Date  ICMJE March 17, 2018
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
  • 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
  • Part B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: Approximately 1 year from end of Week 26 of Part A ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Original Primary Outcome Measures  ICMJE
 (submitted: November 16, 2017)
  • 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 (CAgD) 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.
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
  • 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
  • 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.
  • 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.
  • 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.
  • Part A: Percentage of Participants With Solicited Symptomatic Anemia at End of Treatment (EOT) [ Time Frame: At Part A EOT (Day 182) ]
    Symptomatic anemia is defined as fatigue, weakness, shortness of breath, palpitations, fast heart beat, light headedness, and/or chest pain.
  • Part B: Mean Change From Week 27 in Hemoglobin (Hgb) Level [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
    Mean change from week 27 (Part B baseline) in Hemoglobin (Hgb) level up to Week 77 will be assessed
  • Part B: Mean Change From Week 27 in Bilirubin (total) [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
    Mean change from week 27 (Part B baseline) in Bilirubin (total) level up to Week 77 will be assessed.
  • Part B: Mean Change From Week 27 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
    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.
  • Part B: Mean Change From Week 27 in five level EuroQol five dimensions questionnaire (EQ-5D-5L) [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
    The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. A scale with score 0-100 is used to collect response on current health status. Higher the score better the health.
  • Part B: Mean Change From Week 27 in 12-item short form survey (SF-12) [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
    SF-12 health survey is a self-reported questionnaire to measure participant's profile of functional health and well-being. It includes 12 questions (Q).
  • Part B: Patient's Global Impression of [Fatigue] Severity (PGIS) total score in different timepoints [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
    PGIS is a 5-point response to the severity of the fatigue over the past weeks where 1 indicates No fatigue" to 5 as "very severe". The assessments will be performed every 3 months beginning after Week 27 up to Week 77.
  • Part B: Patient's Global Impression of Change (PGIC) total score in different timepoints [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
    PGIC is a 7-point response to the change of overall status of quality of life where 1 indicates "Very much improved" to 7 as "very much worse". The assessments will be performed every 3 months beginning after Week 27 up to Week 77.
  • Part B: Mean Change From Week 27 in Lactate Dehydrogenase (LDH) level [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
    Mean change from week 27 (Part B baseline) in LDH level up to Week 77 will be assessed
  • Part B: Number of transfusions [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
  • Part B: Mean Change From Week 27 in Haptoglobin [ Time Frame: From Week 27 (Part B baseline) up to Week 77 ]
    Mean change from Week 27 (Part B baseline) in Haptoglobin up to Week 77 will be assessed
  • Part B: Number of healthcare visits by type [ Time Frame: Approximately 1 year from end of Week 26 of Part A ]
    Number of healthcare visits by type such as office visit, hospital ER visit, hospitalization, and ICU stay will be reported for the approximately 1 year duration of Part B
Original Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description The planned total study duration per patient is approximately 1.5 to 2.5 years.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cold Agglutinin Disease
Intervention  ICMJE
  • Drug: sutimlimab (BIVV009)
    Pharmaceutical form:solution for injection Route of administration: intravenous(i.v.)
  • Drug: placebo
    Pharmaceutical form:solution for injection Route of administration: intravenous(i.v.)
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: sutimlimab (BIVV009)
    • Drug: placebo
  • 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.
    Intervention: Drug: sutimlimab (BIVV009)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 16, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   France,   Germany,   Israel,   Italy,   Japan,   Netherlands,   Norway,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03347422
Other Study ID Numbers  ICMJE EFC16216
2017-003539-12 ( EudraCT Number )
BIVV009-04 ( Other Identifier: Bioverativ Therapeutics Inc. )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi ( Bioverativ, a Sanofi company )
Study Sponsor  ICMJE Bioverativ, a Sanofi company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP