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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03347422
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 Without A Recent History of Blood Transfusion
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
Cadenza
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cold Agglutinin Disease 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 (BIVV009)
Treatment: Drugs - placebo

Experimental: BIVV009/BIVV009 - Participants with primary CAD and without a recent history of blood transfusion during the last 6 months prior to enrollment in this study, received an intravenous (IV) infusion of BIVV009 6.5 g (for participants less than \[\<\]75 kilograms \[kg\]) or 7.5 g dose (for participants 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), received placebo on Week 26 and continued to receive BIVV009 6.5 or 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks (for 6.5 g) or 121 weeks (for 7.5 g). All participants who completed Part A elected to continue in Part B.

Experimental: Placebo/BIVV009 - Participants with primary CAD and without a recent history of blood transfusion during the last 6 months prior to enrollment in this study, received an IV infusion of placebo matched to BIVV009 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) received BIVV009 6.5 (if \<75 kg) or 7.5 g (if \>=75 kg) in Part B, on Week 26 and Week 27 and every 2 weeks thereafter for up to an additional 123 weeks (for 6.5 g) or 137 weeks (for 7.5 g). All participants who completed Part A elected to continue in Part B.


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

Treatment: Drugs: placebo
Pharmaceutical form: solution for injection Route of administration: intravenous (i.v.)

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 (AEs) and Serious AEs (SAEs)
Timepoint [2] 0 0
Part B, 6.5 g cohort: From first dose (Week 26) up to 149 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 184); Part B, 7.5 g cohort: From first dose (Week 26) up to 137 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 172)
Secondary outcome [1] 0 0
Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint
Timepoint [1] 0 0
Baseline (Week 0), 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 at the Treatment Assessment Timepoint
Timepoint [2] 0 0
Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Secondary outcome [3] 0 0
Part A: Mean Change From Baseline in Total Bilirubin Levels at the Treatment Assessment Timepoint
Timepoint [3] 0 0
Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Secondary outcome [4] 0 0
Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint
Timepoint [4] 0 0
Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Secondary outcome [5] 0 0
Part A: Percentage of Participants With Solicited Symptomatic Anemia at Week 26
Timepoint [5] 0 0
Week 26
Secondary outcome [6] 0 0
Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points
Timepoint [6] 0 0
Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
Secondary outcome [7] 0 0
Part B: Change From Baseline in Total Bilirubin Levels at Each Specified Time Points
Timepoint [7] 0 0
Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
Secondary outcome [8] 0 0
Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Each Specified Time Points
Timepoint [8] 0 0
Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
Secondary outcome [9] 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 [9] 0 0
Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
Secondary outcome [10] 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 Each Specified Time Points
Timepoint [10] 0 0
Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
Secondary outcome [11] 0 0
Part B: Number of Participants With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Each Specified Time Points
Timepoint [11] 0 0
Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
Secondary outcome [12] 0 0
Part B: Number of Participants With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Each Specified Time Points
Timepoint [12] 0 0
Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184)
Secondary outcome [13] 0 0
Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points
Timepoint [13] 0 0
Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
Secondary outcome [14] 0 0
Part B: Number of Blood Transfusions Per Participant
Timepoint [14] 0 0
From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
Secondary outcome [15] 0 0
Part B: Mean Change From Baseline in Haptoglobin Values at Each Specified Time Points
Timepoint [15] 0 0
Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
Secondary outcome [16] 0 0
Part B: Number of Healthcare Visits by Type
Timepoint [16] 0 0
From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)

Eligibility
Key inclusion criteria
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, and e) Immunoglobulin G DAT less than or equal to (<=) 1+, and, f) No overt malignant disease.
* 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
Exclusion criteria:

* Cold agglutinin syndrome secondary to infection, rheumatologic disease, or active hematologic malignancy.
* History of blood transfusion within 6 months of screening, or history of more than one blood transfusion within 12 months of screening.
* Clinically relevant infection of any kind within the month preceding enrollment (example, 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 would be adjudicated on a case-by-case basis during the confirmatory review of participant eligibility.
* Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at screening.
* Positive human immunodeficiency virus 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 was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

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
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,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
Country [4] 0 0
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
Country [40] 0 0
Spain
State/province [40] 0 0
Madrid
Country [41] 0 0
Spain
State/province [41] 0 0
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
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

No documents have been uploaded by study researchers.