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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03347396




Registration number
NCT03347396
Ethics application status
Date submitted
16/11/2017
Date registered
20/11/2017
Date last updated
2/06/2020

Titles & IDs
Public title
A Study to Assess the Efficacy and Safety of BIVV009 (Sutimlimab) in Participants With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion (Cardinal Study)
Scientific title
A Phase 3, Pivotal, Open-label, Multicenter Study to Assess the Efficacy and Safety of Sutimlimab in Patients With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion
Secondary ID [1] 0 0
BIVV009-03
Secondary ID [2] 0 0
EFC16215
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

Experimental: Sutimlimab - Participants will receive an intravenous (IV) infusion of sutimlimab. Participants who complete Part A per protocol through the end of treatment visit (Day 182) will participate in Part B, and continue to receive sutimlimab up to 1 year after last patient out (LPO) in Part A.


Treatment: Drugs: Sutimlimab
Sutimlimab will be administered as IV infusion.

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 who meets all of the following criteria will be considered a responder: who did not receive a blood transfusion from Week 5 through Week 26 (end of treatment) and did not receive treatment for cold agglutinin disease (CAD) beyond what is permitted per protocol. Additionally the participant's hemoglobin (Hgb) level must meet either of the following criteria: Hgb level greater than or equal to (>=) 12 gram per deciliter (g/dL) at the treatment assessment endpoint, or Hgb increased >= 2 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 Bilirubin up to Week 26 - Mean change from baseline in bilirubin 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 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 [2] 0 0
Baseline up to Week 26
Secondary outcome [3] 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 [3] 0 0
Baseline up to Week 26
Secondary outcome [4] 0 0
Part A: Number of Blood Transfusions After the First 5 Weeks of Study Drug Administration - Number of transfusions after the first 5 weeks of study drug administration will be assessed.
Timepoint [4] 0 0
5 Weeks
Secondary outcome [5] 0 0
Part A: Number of Blood Units Transfused After the First 5 Weeks of Study Drug Administration - Number of blood units transfused after the first 5 weeks of study drug administration will be assessed.
Timepoint [5] 0 0
5 Weeks
Secondary outcome [6] 0 0
Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level up to Week 26 - Mean change from baseline in Hgb level up to Week 26 will be assessed.
Timepoint [6] 0 0
Baseline up to Week 26

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; e) Immunoglobulin G (IgG) DAT less than or equal to (<=) 1+,
and f) No overt malignant disease

- History of at least one documented blood transfusion within 6 months of enrollment

- 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 (eg,
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 (eg, with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6
months prior to enrollment

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
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
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 postcode(s) [1] 0 0
4556 - Buderim
Recruitment postcode(s) [2] 0 0
3350 - Ballarat
Recruitment postcode(s) [3] 0 0
3168 - Clayton
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
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Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Austria
State/province [10] 0 0
Vienna
Country [11] 0 0
Belgium
State/province [11] 0 0
Antwerpen
Country [12] 0 0
Belgium
State/province [12] 0 0
La Louvière
Country [13] 0 0
Belgium
State/province [13] 0 0
Leuven
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
Canada
State/province [16] 0 0
Edmonton
Country [17] 0 0
France
State/province [17] 0 0
Caen
Country [18] 0 0
France
State/province [18] 0 0
Créteil
Country [19] 0 0
France
State/province [19] 0 0
Lyon
Country [20] 0 0
Germany
State/province [20] 0 0
Dresden
Country [21] 0 0
Germany
State/province [21] 0 0
Essen
Country [22] 0 0
Germany
State/province [22] 0 0
Ulm
Country [23] 0 0
Israel
State/province [23] 0 0
Jerusalem
Country [24] 0 0
Israel
State/province [24] 0 0
Netanya
Country [25] 0 0
Israel
State/province [25] 0 0
Tel Aviv
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
Kanagawa
Country [31] 0 0
Japan
State/province [31] 0 0
Saitama-Ken
Country [32] 0 0
Japan
State/province [32] 0 0
Tokyo-To
Country [33] 0 0
Netherlands
State/province [33] 0 0
Amsterdam
Country [34] 0 0
Norway
State/province [34] 0 0
Bergen
Country [35] 0 0
Norway
State/province [35] 0 0
Oslo
Country [36] 0 0
Norway
State/province [36] 0 0
Trondheim
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Spain
State/province [37] 0 0
Madrid
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Spain
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Barcelona
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Spain
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Sevilla
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Spain
State/province [40] 0 0
Valencia
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Leeds
Country [42] 0 0
United Kingdom
State/province [42] 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 (>=) 2 gram per deciliter (g/dL) increase in hemoglobin (Hgb) levels or
increases Hgb to >= 12 g/dL and obviates the need for blood transfusion during treatment in
participants with primary cold agglutinin disease (CAD) who have 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 CAD.
Trial website
https://clinicaltrials.gov/show/NCT03347396
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