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Cadenza: 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

Sponsor
Bioverativ, a Sanofi company (Industry)
Overall Status
Completed
CT.gov ID
NCT03347422
Collaborator
(none)
42
Enrollment
53
Locations
2
Arms
44.6
Actual Duration (Months)
0.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: sutimlimab (BIVV009)
  • Drug: placebo
 Phase 3

Detailed Description

The planned total study duration per patient is approximately 1.5 to 2.5 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 17, 2018
Actual Primary Completion Date :
Dec 3, 2021
Actual Study Completion Date :
Dec 3, 2021

Arms and Interventions

Arm Intervention/Treatment
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.

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.)
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.

Drug: sutimlimab (BIVV009)
Pharmaceutical form:solution for injection Route of administration: intravenous(i.v.)

Outcome Measures

Primary Outcome Measures

  1. Part A: Percentage of Participants With Response (R) [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

  2. Part B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs) [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.

Secondary Outcome Measures

  1. Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level up to Week 26 [Baseline Up to Week 26]

    Mean change from baseline in hemoglobin (Hgb) level up to Week 26 will be assessed

  2. Part A: Mean Change From Baseline in Bilirubin up to Week 26 [Baseline up to Week 26]

    Mean change from baseline in bilirubin up to Week 26 will be assessed.

  3. Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) [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.

  4. Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) up to Week 26 [Baseline up to Week 26]

    Mean change from baseline in LDH up to Week 26 will be assessed.

  5. Part A: Percentage of Participants With Solicited Symptomatic Anemia at End of Treatment (EOT) [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.

  6. Part B: Mean Change From Week 27 in Hemoglobin (Hgb) Level [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

  7. Part B: Mean Change From Week 27 in Bilirubin (total) [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.

  8. Part B: Mean Change From Week 27 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) [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.

  9. Part B: Mean Change From Week 27 in five level EuroQol five dimensions questionnaire (EQ-5D-5L) [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.

  10. Part B: Mean Change From Week 27 in 12-item short form survey (SF-12) [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).

  11. Part B: Patient's Global Impression of [Fatigue] Severity (PGIS) total score in different timepoints [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.

  12. Part B: Patient's Global Impression of Change (PGIC) total score in different timepoints [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.

  13. Part B: Mean Change From Week 27 in Lactate Dehydrogenase (LDH) level [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

  14. Part B: Number of transfusions [From Week 27 (Part B baseline) up to Week 77]

  15. Part B: Mean Change From Week 27 in Haptoglobin [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

  16. Part B: Number of healthcare visits by type [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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
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 (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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Arizona Oncology Associates PC Tucson Arizona United States 85711
2 USC/Keck School of Medicine Los Angeles California United States 90033
3 Georgetown University Medical Center Georgetown District of Columbia United States 20007
4 Cleveland Clinic Florida Weston Florida United States 33331
5 Massachusetts General Hospital Boston Massachusetts United States 02114
6 Brigham and Women's Hospital Boston Massachusetts United States 02115
7 Washington University School of Medicine Saint Louis Missouri United States 63110
8 Montefiore Medical Center New York New York United States 10461
9 New York Medical College at Westchester Medical Center Valhalla New York United States 10595
10 East Carolina University Greenville North Carolina United States 27834
11 Cleveland Clinic Cleveland Ohio United States 44195
12 Hospital of the University of Pennsylvania Philadelphia Pennsylvania United States 19104
13 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15232
14 UW Hospitals and Clinics Madison Wisconsin United States 53792
15 USC Health Clinics Buderim Queensland Australia 4556
16 Ballarat Oncology & Haematology Ballarat Victoria Australia 3350
17 Monash Medical Centre Clayton Victoria Australia 3168
18 Perth Blood Institute West Perth Western Australia Australia 6005
19 Medical University of Vienna Vienna Austria 1090
20 ZNA Stuivenberg Antwerpen Belgium 2060
21 University Hospitals Leuven Leuven Belgium 3000
22 St. Michael's Hospital Toronto Ontario Canada M5B1W8
23 McGill University Health Center Montréal Quebec Canada H4A3J1
24 CHU d'Angers Angers Cedex 9 France 49933
25 Hôpital de Caen Caen France 14033
26 Centre Hospitalier Henri Mondor Créteil France 94000
27 Centre Hospitalier Lyon Sud Pierre-Bénite France 69495
28 Gemeinschaftspraxis Hämatologie-Onkologie Dresden Germany 1307
29 Universitätsklinikum Essen Essen Germany 45147
30 Univ Ulm, Inst Klin. Transfusions. Immungen Ulm Germany 89081
31 Hadassah Medical Center Jerusalem Israel 91120
32 Laniado Hospital Netanya Israel 4244916
33 A. O. Spedali Civili di Brescia Brescia Italy 25123
34 Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico Milan Italy 20122
35 U.O.C. Ematologia- Policlinico "A. Gemelli" Rome Italy 00168
36 U.O.C. Ematologia Ospedale San Bortolo Vicenza Italy 36100
37 Japanese Red Cross Society Himeji Hospital Himeji Hyogo Japan 670-8540
38 Ishikawa Prefectural Central Hospital Kanazawa Ishikawa-ken Japan 9208530
39 Tokai University Hospital Isehara Kanagawa Japan 259-1193
40 Osaka University Hospital Suita Osaka Japan 565-0871
41 Saitama Medical University Hospital Iruma-gun Saitama-Ken Japan 350-0495
42 Aichi Medical University Hospital Nagakute Japan 480-1195
43 Academisch Medisch Centrum Amsterdam Netherlands 1105
44 Leids Universitair Medisch Centrum Leiden Netherlands 2333
45 Haukeland University Hospital Bergen Norway 5053
46 St Olavs Hospital, Avdeling for blodsykdommer Trondheim Norway 7030
47 Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain 28222
48 Hospital Clinci i Provincial de Barcelona Barcelona Spain 08036
49 Hospital Universitario Virgen del Rocio Sevilla Spain 41013
50 Hospital Universitario Dr. Peset Valencia Spain 46017
51 St James Hospital, Leeds Leeds United Kingdom LS9 7TF
52 Imperial College Healthcare NHS Trust, Hammersmith Hospital London United Kingdom W12 0HS
53 University College London London United Kingdom WC1E 6AG

Sponsors and Collaborators

  • Bioverativ, a Sanofi company

Investigators

  • Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Bioverativ, a Sanofi company
ClinicalTrials.gov Identifier:
NCT03347422
Other Study ID Numbers:
  • EFC16216
  • 2017-003539-12
  • BIVV009-04
First Posted:
Nov 20, 2017
Last Update Posted:
Apr 25, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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

Study Results

No Results Posted as of Apr 25, 2022