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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03347422




Registration number
NCT03347422
Ethics application status
Date submitted
16/11/2017
Date registered
20/11/2017
Date last updated
24/04/2020

Titles & IDs
Public title
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 Study)
Scientific 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
Secondary ID [1] 0 0
2017-003539-12
Secondary ID [2] 0 0
EFC16216
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Agglutinin Disease, Cold 0 0
Condition category
Condition code
Blood 0 0 0 0
Anaemia
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sutimlimab
Treatment: Drugs - Placebo

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.

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.


Treatment: Drugs: Sutimlimab
Sutimlimab will be administered by IV.

Treatment: Drugs: Placebo
Placebo will be administered by IV.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Percentage of Participants With Response (R) - 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) at treatment assessment endpoint.
Timepoint [1] 0 0
Up to Week 26
Primary outcome [2] 0 0
Part B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs) - An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Timepoint [2] 0 0
Approximately 1 year
Secondary outcome [1] 0 0
Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level up to Week 26 - Mean change from baseline in hemoglobin (Hgb) level up to Week 26 will be assessed.
Timepoint [1] 0 0
Baseline Up to Week 26
Secondary outcome [2] 0 0
Part A: Mean Change From Baseline in Bilirubin up to Week 26 - Mean change from baseline in bilirubin up to Week 26 will be assessed.
Timepoint [2] 0 0
Baseline up to Week 26
Secondary outcome [3] 0 0
Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) - 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.
Timepoint [3] 0 0
Baseline up to Week 26
Secondary outcome [4] 0 0
Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) up to Week 26 - Mean change from baseline in LDH up to Week 26 will be assessed.
Timepoint [4] 0 0
Baseline up to Week 26
Secondary outcome [5] 0 0
Part A: Percentage of Participants With Solicited Symptomatic Anemia at End of Treatment (EOT) - Symptomatic anemia is defined as fatigue, weakness, shortness of breath, palpitations, fast heart beat, light headedness, and/or chest pain.
Timepoint [5] 0 0
At EOT (Day 182)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
USC Health Clinics - Buderim
Recruitment hospital [2] 0 0
Ballarat Oncology & Haematology - Ballarat
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
Perth Blood Institute - West Perth
Recruitment postcode(s) [1] 0 0
4556 - Buderim
Recruitment postcode(s) [2] 0 0
3350 - Ballarat
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
6005 - West Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
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United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Austria
State/province [12] 0 0
Vienna
Country [13] 0 0
Belgium
State/province [13] 0 0
Antwerpen
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
France
State/province [17] 0 0
Angers Cedex 9
Country [18] 0 0
France
State/province [18] 0 0
Caen
Country [19] 0 0
France
State/province [19] 0 0
Créteil
Country [20] 0 0
France
State/province [20] 0 0
Pierre-Bénite
Country [21] 0 0
Germany
State/province [21] 0 0
Dresden
Country [22] 0 0
Germany
State/province [22] 0 0
Essen
Country [23] 0 0
Germany
State/province [23] 0 0
Ulm
Country [24] 0 0
Israel
State/province [24] 0 0
Jerusalem
Country [25] 0 0
Israel
State/province [25] 0 0
Netanya
Country [26] 0 0
Italy
State/province [26] 0 0
Brescia
Country [27] 0 0
Italy
State/province [27] 0 0
Milan
Country [28] 0 0
Italy
State/province [28] 0 0
Rome
Country [29] 0 0
Italy
State/province [29] 0 0
Vicenza
Country [30] 0 0
Japan
State/province [30] 0 0
Hyogo
Country [31] 0 0
Japan
State/province [31] 0 0
Ishikawa-ken
Country [32] 0 0
Japan
State/province [32] 0 0
Kanagawa
Country [33] 0 0
Japan
State/province [33] 0 0
Osaka
Country [34] 0 0
Japan
State/province [34] 0 0
Saitama-Ken
Country [35] 0 0
Japan
State/province [35] 0 0
Nagakute
Country [36] 0 0
Netherlands
State/province [36] 0 0
Amsterdam
Country [37] 0 0
Netherlands
State/province [37] 0 0
Leiden
Country [38] 0 0
Norway
State/province [38] 0 0
Bergen
Country [39] 0 0
Norway
State/province [39] 0 0
Trondheim
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Spain
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Madrid
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Spain
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Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Sevilla
Country [43] 0 0
Spain
State/province [43] 0 0
Valencia
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Leeds
Country [45] 0 0
United Kingdom
State/province [45] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bioverativ, a Sanofi company
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03347422
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications