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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03347396
Ethics application status
Date submitted
16/11/2017
Date registered
20/11/2017

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 - BIVV009

Experimental: BIVV009 - Participants with primary CAD who had a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an intravenous (IV) infusion of BIVV009 6.5 grams (g) (if body weight was less than \[\<\] 75 kilograms \[kg\]) or BIVV009 7.5 g (if body weight was greater than or equal to \[\>=\] 75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.


Treatment: Drugs: BIVV009
Sutimlimab was administered as intravenous (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 to Treatment
Timepoint [1] 0 0
From Week 5 through Week 26
Primary outcome [2] 0 0
Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Timepoint [2] 0 0
Part B, 6.5 g cohort: From first dose (Week 27) up to 143 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 179); Part B, 7.5 g cohort: From first dose (Week 27) up to 149 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 185)
Secondary outcome [1] 0 0
Part A: Mean Change From Baseline in Bilirubin Levels at the Treatment Assessment Timepoint
Timepoint [1] 0 0
Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 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) at Treatment Assessment Timepoint
Timepoint [2] 0 0
Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Secondary outcome [3] 0 0
Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint
Timepoint [3] 0 0
Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Secondary outcome [4] 0 0
Part A: Number of Blood Transfusions Per Participant
Timepoint [4] 0 0
From Week 5 up to Week 26
Secondary outcome [5] 0 0
Part A: Number of Blood Units Transfused Per Participant
Timepoint [5] 0 0
From Week 5 up to Week 26
Secondary outcome [6] 0 0
Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint
Timepoint [6] 0 0
Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Secondary outcome [7] 0 0
Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points
Timepoint [7] 0 0
Baseline, Weeks 27,29,31,33,35,37,39,41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)
Secondary outcome [8] 0 0
Part B: Change From Baseline in Bilirubin Levels at Each Specified Time Points
Timepoint [8] 0 0
Baseline, Weeks 27,29,31,33,35,37,39,41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)
Secondary outcome [9] 0 0
Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and Early Termination (ET) Visit/Safety Follow-up Visit
Timepoint [9] 0 0
Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU visit (i.e., up to Week 185)
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135 and ET Visit/SFU visit (i.e., up to Week 185)
Secondary outcome [11] 0 0
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 Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU Visit
Timepoint [11] 0 0
Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU visit (i.e., up to Week 185)
Secondary outcome [12] 0 0
Part B: Number of Participants With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU Visit
Timepoint [12] 0 0
At Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU visit (i.e., up to Week 185)
Secondary outcome [13] 0 0
Part B: Number of Participants With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU Visit
Timepoint [13] 0 0
At Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU visit (i.e., up to Week 185)
Secondary outcome [14] 0 0
Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points
Timepoint [14] 0 0
Baseline, Weeks 27,29,31,33,35,37,39,41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)
Secondary outcome [15] 0 0
Part B: Number of Blood Transfusions Per Participant
Timepoint [15] 0 0
From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
Secondary outcome [16] 0 0
Part B: Number of Blood Units Transfused Per Participant
Timepoint [16] 0 0
From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
Secondary outcome [17] 0 0
Part B: Change From Baseline in Haptoglobin Values at Each Specified Time Points
Timepoint [17] 0 0
Baseline, Weeks 27,29,31,33,35,37,39,41,43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)
Secondary outcome [18] 0 0
Part B: Number of Healthcare Visits by Type
Timepoint [18] 0 0
From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)

Eligibility
Key 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; 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 g/dL.
* Bilirubin level above the normal reference range, including participants with Gilbert's Syndrome.
Minimum age
18 Years
Maximum age
No limit
Sex
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 (e.g., 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 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 (e.g., with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Completed
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
Country [4] 0 0
United States of America
State/province [4] 0 0
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
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Sevilla
Country [40] 0 0
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Alexander Röth, Wilma Barcellini, Shirley D'Sa, Yo... [More Details]