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CompletedNCT03347422CadenzaUpdated Dec 23, 2022Results posted

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

A Phase 3 interventional study of sutimlimab (BIVV009) and placebo in Cold Agglutinin Disease, sponsored by Bioverativ, a Sanofi company. Completed at 53 sites in 14 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-12-23.

Sponsored by Bioverativ, a Sanofi company · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
42
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of Part A was to determine whether sutimlimab administration resulted in a greater than or equal to (>=)1.5 grams 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 was to evaluate the long-term safety and tolerability of sutimlimab in participants with primary CAD.

Read the detailed description

The planned total study duration per participant was approximately 1.5 to 2.5 years.

02

Conditions studied

  • Cold Agglutinin Disease
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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.

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.

04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
42 participants (actual)

Study arms

  • 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.

    Drug: sutimlimab (BIVV009)

  • 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.

    Drug: sutimlimab (BIVV009) · Drug: placebo

Interventions

  • Drugsutimlimab (BIVV009)

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

  • Drugplacebo

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

05

What researchers measure

Primary outcomes

  1. Part A: Percentage of Participants With Response to Treatment

    A participant was considered a responder: if he or she did not receive blood transfusion from Week 5 through Week 26 (end of treatment) and did not receive treatment for CAD beyond what was permitted per protocol. Additionally, participant's hemoglobin (Hgb) level must have increased to \>=1.5 grams per deciliter (g/dL) from baseline (defined as last Hgb value before administration of first dose of study drug) at treatment assessment timepoint (defined as average of values from the Week 23, 25, and 26 visits). Percentage of responders was calculated together with 95% exact Clopper-Pearson confidence interval (CI).

    Time frame: From Week 5 through Week 26

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

    Adverse Event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Treatment emergent serious adverse events (TESAEs) was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, was medically important event. Treatment emergent adverse events (TEAEs): AEs that developed, worsened or became serious during the treatment-emergent (TE) period (from first investigational medicinal product \[IMP\] administration in Part B to last IMP administration + 9 weeks follow-up period).

    Time frame: 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 outcomes

  1. Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint

    Mean change from baseline (Week 0) in Hemoglobin (Hgb) at the treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. Least squares (LS) mean and 95 % confidence interval (CI) was assessed by Mixed Model for Repeated Measures (MMRM) approach using heterogeneous Toeplitz (TOEPH) covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.

    Time frame: Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

  2. Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at the Treatment Assessment Timepoint

    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 were added to obtain a total score. Total score ranged from 0 to 52, with higher score indicating more fatigue. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline (Week 0) as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.

    Time frame: Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

  3. Part A: Mean Change From Baseline in Total Bilirubin Levels at the Treatment Assessment Timepoint

    Mean change from baseline (Week 0) in total bilirubin at the treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. Baseline was defined as the last non-missing value prior to the first administration of study drug.

    Time frame: Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

  4. Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint

    Mean change from baseline (Week 0) in LDH at the treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. Baseline was defined as the last non-missing value prior to the first administration of study drug.

    Time frame: Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

  5. Part A: Percentage of Participants With Solicited Symptomatic Anemia at Week 26

    Symptomatic anemia was defined as having following symptoms: i. Fatigue; ii. Weakness; iii. Shortness of breath; iv. Palpitations, fast heartbeat; v. Light headedness and/or vi. Chest pain. Percentage of participants with solicited symptomatic anemia symptoms was reported in this outcome measure.

    Time frame: Week 26

  6. Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points

    Change from baseline (Week 0) in Hgb levels at each specified time points (i.e., Week 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, 81, 83,85,87, 89,91, 93, 95, 97, 99,101,103, 105, 107,109, 111,113,115,117,119, 121,123, 125, 127,129,131,133,135,137,139,141,143,145,147,149,151,153, 155,157,159,161,163,165,167,169,171,173,175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. Early Termination (ET) visit/safety follow up (SFU) visit was 9 weeks after administration of last dose (i.e., up to Week 184). Here, "0" in the number analyzed field signifies that none of participants were available for assessment at the specified timepoints.

    Time frame: Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)

  7. Part B: Change From Baseline in Total Bilirubin Levels at Each Specified Time Points

    Change from baseline (Week 0) in total bilirubin levels at each specified time points (i.e., Week 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, 81,83, 85, 87, 89, 91, 93, 95, 97, 99,101,103, 105, 107,109, 111,113,115,117,119, 121, 123, 125, 127,129,131,133,135,137,139,141,143, 145,147,149,151,153,155,157,159, 161,163,165,167,169,171,173,175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184). Here, "0" in the number analyzed field signifies that none of participants were available for assessment at the specified timepoints.

    Time frame: Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)

  8. Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Each Specified Time Points

    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 were added to obtain a total score. The Total score ranged from 0 to 52, with higher score indicating more fatigue. Baseline (Week 0) was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184).

    Time frame: 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)

  9. 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

    SF-12: 12 item-questionnaire assessed health-related quality of life (HRQOL), contained 12 items, categorized into 8 domains (subscales) of functioning and well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality and social functioning, with each domain score ranged from 0 (poor health) to 100 (better health). Higher scores = good health condition. These 8 domains were further summarized into 2 summary scores, PCS and MCS that ranged from 0 (poor health) to 100 (better health). Higher scores = better HRQOL. Baseline (Week 0): last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit: 9 weeks after administration of last dose (i.e., up to Week 184).

    Time frame: 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)

  10. 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

    EQ-5D-5L included 2 components: health state utility index (descriptive system) and Visual Analog Scale (VAS). EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response option: no problem, slight problem, moderate problem, severe problem and extreme problems measured with Likert scale. EQ-5D-5L responses converted into single index utility score between 0 to 1. Higher score=better health. EQ-5D-5L VAS rated participant's current health state on scale from 0 (worst imaginable health) to 100 (best imaginable health). Baseline (Week 0): last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit: 9 weeks after administration of last dose (i.e., up to Week 184).

    Time frame: 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)

  11. Part B: Number of Participants With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Each Specified Time Points

    The PGIS is a self-reported scale. The PGIS is a 1-item questionnaire designed to assess participant's impression of disease severity using a 5-point scale ranging from 1 to 5, where 1=none, 2=mild, 3=moderate, 4=severe, 5=very severe. Higher scores indicated greater severity. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184).

    Time frame: 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)

  12. Part B: Number of Participants With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Each Specified Time Points

    PGIC is a self-administered questionnaire to evaluate the improvement or worsening compared to the start of the study. PGIC was assessed on a 7-point Likert scale ranged from 1 (greatly improved) to 7 (greatly worsened). Categories were defined based on the PGIC scores as follows: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse and 7=very much worsen. Higher scores indicated greater severity. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184).

    Time frame: 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)

  13. Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points

    Change from baseline (Week 0) in LDH levels at each specified time points (i.e., Week 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, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107,109, 111, 113, 115, 117, 119, 121,123, 125, 127,129,131,133,135,137,139,141,143,145,147, 149, 151,153,155,157,159,161,163,165,167,169, 171, 173, 175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184).

    Time frame: Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)

  14. Part B: Number of Blood Transfusions Per Participant

    A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was \<9 g/dL and the participant had symptoms of anemia or Hgb was \<7 g/dL and the participant was asymptomatic.

    Time frame: From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)

  15. Part B: Mean Change From Baseline in Haptoglobin Values at Each Specified Time Points

    Change from baseline (Week 0) in haptoglobin values at each specified time points (i.e., Week 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, 81, 83, 85, 87, 89, 91, 93, 95, 97,99,101,103, 105, 107,109, 111,113,115,117,119, 121,123, 125, 127, 129,131,133,135,137,139,141,143, 145,147,149,151,153,155,157,159, 161,163,165,167,169,171,173,175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184). Haptoglobin values \<0.2 were imputed as 0.2.

    Time frame: Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)

  16. Part B: Number of Healthcare Visits by Type

    In this outcome measure, number of healthcare visits which included non-study healthcare resource utilization visit (consisted mainly of extra visits to the office of the study doctor, visit to a generalist doctor or visit to a specialist doctor), hospitalization visit and visit to hospital emergency is reported.

    Time frame: From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)

06

Results

Posted Dec 23, 2022

Participant flow

The study was conducted at 27 sites in 13 countries. Out of 66 screened participants, a total of 42 participants were enrolled and randomized from 17 March 2018 to 30 March 2020. This study consisted of 2 Parts: Part A and Part B.

Part A (26 Weeks)
Participant flow — Part A (26 Weeks)
MilestoneBIVV009/BIVV009Placebo/BIVV009
Started2220
Completed1920
Not completed30
Withdrew: Adverse event30
Part B (149 Weeks)
Participant flow — Part B (149 Weeks)
MilestoneBIVV009/BIVV009Placebo/BIVV009
Started1920
Completed1616
Not completed34
Withdrew: Lack of efficacy12
Withdrew: Adverse event01
Withdrew: Withdrawal by subject11
Withdrew: Other10

Outcome measures

PrimaryPart A: Percentage of Participants With Response to Treatment

A participant was considered a responder: if he or she did not receive blood transfusion from Week 5 through Week 26 (end of treatment) and did not receive treatment for CAD beyond what was permitted per protocol. Additionally, participant's hemoglobin (Hgb) level must have increased to \>=1.5 grams per deciliter (g/dL) from baseline (defined as last Hgb value before administration of first dose of study drug) at treatment assessment timepoint (defined as average of values from the Week 23, 25, and 26 visits). Percentage of responders was calculated together with 95% exact Clopper-Pearson confidence interval (CI).

Time frame:
From Week 5 through Week 26
Reported as:
Number · percentage of participants
Part A: Percentage of Participants With Response to Treatment
percentage of participantsBIVV009Placebo
Part A: Percentage of Participants With Response to Treatment72.7 (49.8 to 89.3)15.0 (3.2 to 37.9)
Statistical analysis
  • BIVV009 vs Placebo · Cochran-Mantel-Haenszel · p = <0.001 (Threshold for significance was 0.05.) · Odds ratio (or): 15.94 · 95% CI 2.88 to 88.04Stratified by baseline hemoglobin (\< median versus \>=median) and geographic region (Asia/Other, North America, and Europe).
PrimaryPart B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)

Adverse Event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Treatment emergent serious adverse events (TESAEs) was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, was medically important event. Treatment emergent adverse events (TEAEs): AEs that developed, worsened or became serious during the treatment-emergent (TE) period (from first investigational medicinal product \[IMP\] administration in Part B to last IMP administration + 9 weeks follow-up period).

Time frame:
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)
Reported as:
Count of participants · Participants
Part B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
ParticipantsPart B: BIVV009 6.5 gPart B: BIVV009 7.5 g
TEAEs297
TESAEs61
SecondaryPart A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint

Mean change from baseline (Week 0) in Hemoglobin (Hgb) at the treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. Least squares (LS) mean and 95 % confidence interval (CI) was assessed by Mixed Model for Repeated Measures (MMRM) approach using heterogeneous Toeplitz (TOEPH) covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.

Time frame:
Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Reported as:
Least squares mean · grams per deciliter
Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint
grams per deciliterBIVV009Placebo
Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint2.66 (2.09 to 3.22)0.09 (-0.50 to 0.68)
Statistical analysis
  • BIVV009 vs Placebo · Mixed model for repeated measures · p = <0.001 (Threshold of significance at 0.05 level.) · Ls mean difference: 2.56 · 95% CI 1.75 to 3.38
SecondaryPart A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at the Treatment Assessment Timepoint

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 were added to obtain a total score. Total score ranged from 0 to 52, with higher score indicating more fatigue. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline (Week 0) as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.

Time frame:
Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Reported as:
Least squares mean · score on a scale
Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at the Treatment Assessment Timepoint
score on a scaleBIVV009Placebo
Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at the Treatment Assessment Timepoint10.83 (7.45 to 14.22)1.91 (-1.65 to 5.46)
Statistical analysis
  • BIVV009 vs Placebo · Mixed model for repeated measures · p = <0.001 (Threshold of significance at 0.05 level.) · Ls mean difference: 8.93 · 95% CI 4.00 to 13.85
SecondaryPart A: Mean Change From Baseline in Total Bilirubin Levels at the Treatment Assessment Timepoint

Mean change from baseline (Week 0) in total bilirubin at the treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. Baseline was defined as the last non-missing value prior to the first administration of study drug.

Time frame:
Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Reported as:
Mean · micromoles per liter
Part A: Mean Change From Baseline in Total Bilirubin Levels at the Treatment Assessment Timepoint
micromoles per literBIVV009Placebo
Part A: Mean Change From Baseline in Total Bilirubin Levels at the Treatment Assessment Timepoint-22.881 ± 10.401-1.388 ± 13.901
SecondaryPart A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint

Mean change from baseline (Week 0) in LDH at the treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. Baseline was defined as the last non-missing value prior to the first administration of study drug.

Time frame:
Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Reported as:
Mean · units per liter
Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint
units per literBIVV009Placebo
Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint-150.833 ± 160.8247.600 ± 212.690
SecondaryPart A: Percentage of Participants With Solicited Symptomatic Anemia at Week 26

Symptomatic anemia was defined as having following symptoms: i. Fatigue; ii. Weakness; iii. Shortness of breath; iv. Palpitations, fast heartbeat; v. Light headedness and/or vi. Chest pain. Percentage of participants with solicited symptomatic anemia symptoms was reported in this outcome measure.

Time frame:
Week 26
Reported as:
Number · percentage of participants
Part A: Percentage of Participants With Solicited Symptomatic Anemia at Week 26
percentage of participantsBIVV009Placebo
Fatigue31.668.4
Weakness5.331.6
Shortness of breath5.336.8
Palpitations015.8
Light headedness5.315.8
Chest pain05.3
SecondaryPart B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points

Change from baseline (Week 0) in Hgb levels at each specified time points (i.e., Week 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, 81, 83,85,87, 89,91, 93, 95, 97, 99,101,103, 105, 107,109, 111,113,115,117,119, 121,123, 125, 127,129,131,133,135,137,139,141,143,145,147,149,151,153, 155,157,159,161,163,165,167,169,171,173,175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. Early Termination (ET) visit/safety follow up (SFU) visit was 9 weeks after administration of last dose (i.e., up to Week 184). Here, "0" in the number analyzed field signifies that none of participants were available for assessment at the specified timepoints.

Time frame:
Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
Reported as:
Mean · grams per deciliter
Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points
grams per deciliterBIVV009/BIVV009Placebo/BIVV009
Week 272.647 ± 1.3481.125 ± 1.545
Week 292.507 ± 1.6691.947 ± 1.467
Week 312.490 ± 1.5502.358 ± 1.471
Week 332.519 ± 1.5201.987 ± 2.054
Week 352.611 ± 1.5221.977 ± 2.010
Week 372.197 ± 1.4612.469 ± 1.550
Week 392.528 ± 1.6072.368 ± 1.835
Week 412.162 ± 1.6362.074 ± 1.825
Week 432.436 ± 1.1032.182 ± 1.643
Week 452.644 ± 1.6882.249 ± 1.858
Week 472.335 ± 1.1082.315 ± 2.129
Week 492.531 ± 1.2802.121 ± 1.883
Week 512.349 ± 1.2602.394 ± 1.870
Week 532.346 ± 1.1822.411 ± 1.786
Week 552.438 ± 1.3962.539 ± 1.403
Week 572.531 ± 1.4462.250 ± 1.774
Week 592.590 ± 1.3972.008 ± 2.615
Week 614.073 ± 6.7612.059 ± 1.911
Week 632.382 ± 1.5462.102 ± 1.780
Week 652.925 ± 1.4472.311 ± 1.986
Week 674.170 ± 6.5092.534 ± 2.036
Week 692.777 ± 1.4112.505 ± 2.093
Week 712.654 ± 1.4952.357 ± 1.758
Week 732.800 ± 2.1322.197 ± 1.989
Week 752.391 ± 1.7002.175 ± 2.151
Week 773.074 ± 2.0882.451 ± 1.878
Week 792.614 ± 1.8742.419 ± 2.247
Week 812.598 ± 1.8012.458 ± 1.579
Week 832.469 ± 1.7772.762 ± 1.539
Week 852.755 ± 1.9422.489 ± 1.375
Week 872.477 ± 1.7792.765 ± 1.605
Week 892.551 ± 1.8352.482 ± 2.004
Week 912.380 ± 2.0842.556 ± 1.538
Week 932.931 ± 2.3862.655 ± 2.033
Week 952.262 ± 2.0142.578 ± 1.970
Week 972.413 ± 2.2622.551 ± 1.544
Week 992.019 ± 1.7992.412 ± 1.822
Week 1012.276 ± 1.9862.171 ± 1.852
Week 1032.378 ± 2.3422.527 ± 1.807
Week 1052.291 ± 1.7192.321 ± 1.805
Week 1072.319 ± 1.5112.560 ± 1.858
Week 1092.509 ± 1.7722.645 ± 1.608
Week 1112.416 ± 1.9082.750 ± 1.707
Week 1132.860 ± 1.8322.268 ± 1.497
Week 1152.622 ± 1.9862.326 ± 1.809
Week 1173.135 ± 1.5982.474 ± 1.808
Week 1193.106 ± 1.4932.608 ± 2.045
Week 1213.388 ± 1.6162.325 ± 2.223
Week 1233.255 ± 1.3462.878 ± 2.667
Week 1253.197 ± 1.3661.700 ± 2.684
Week 1273.371 ± 1.5512.102 ± 3.211
Week 1293.171 ± 1.5662.129 ± 2.739
Week 1313.453 ± 1.8231.423 ± 3.184
Week 1333.520 ± 1.7072.025 ± 1.167
Week 1353.611 ± 1.4583.048 ± 1.620
Week 1374.074 ± 2.3922.400 ± 1.808
Week 1393.929 ± 1.8893.334 ± 2.669
Week 1413.500 ± 0.6562.733 ± 1.674
Week 1433.220 ± 1.0642.985 ± 1.904
Week 1453.350 ± 0.6363.467 ± 2.108
Week 1473.202 ± 0.5912.300 ± 0.566
Week 1492.9002.550 ± 0.778
Week 1512.961 ± 0.3703.000
Week 1532.8002.800
Week 1552.7003.600
Week 1572.7003.000
Week 1593.3002.300
Week 1614.1002.400
Week 1634.1002.600
Week 1653.800—
Week 1674.700—
Week 1694.300—
Week 1714.200—
Week 1734.000—
Week 1752.500—
ET/SFU Visit0.149 ± 2.0730.359 ± 1.872
SecondaryPart B: Change From Baseline in Total Bilirubin Levels at Each Specified Time Points

Change from baseline (Week 0) in total bilirubin levels at each specified time points (i.e., Week 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, 81,83, 85, 87, 89, 91, 93, 95, 97, 99,101,103, 105, 107,109, 111,113,115,117,119, 121, 123, 125, 127,129,131,133,135,137,139,141,143, 145,147,149,151,153,155,157,159, 161,163,165,167,169,171,173,175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184). Here, "0" in the number analyzed field signifies that none of participants were available for assessment at the specified timepoints.

Time frame:
Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
Reported as:
Mean · micromoles per liter
Part B: Change From Baseline in Total Bilirubin Levels at Each Specified Time Points
micromoles per literBIVV009/BIVV009Placebo/BIVV009
Week 27-22.965 ± 9.899-18.761 ± 13.353
Week 29-20.119 ± 12.170-19.889 ± 14.500
Week 31-21.675 ± 11.025-22.153 ± 14.962
Week 33-19.860 ± 11.527-24.263 ± 15.169
Week 35-20.540 ± 10.557-21.888 ± 13.930
Week 37-21.350 ± 13.234-22.527 ± 16.315
Week 39-23.493 ± 11.425-21.173 ± 15.901
Week 41-18.694 ± 12.189-21.138 ± 16.150
Week 43-20.593 ± 11.449-21.544 ± 16.603
Week 45-18.556 ± 11.213-20.156 ± 16.757
Week 47-20.400 ± 9.803-20.250 ± 15.536
Week 49-21.450 ± 10.271-21.024 ± 13.630
Week 51-19.686 ± 11.072-19.444 ± 15.942
Week 53-19.107 ± 11.267-20.335 ± 17.126
Week 55-19.354 ± 12.209-23.481 ± 12.300
Week 57-21.708 ± 10.467-18.953 ± 15.825
Week 59-19.979 ± 9.706-19.820 ± 16.209
Week 61-18.254 ± 10.541-21.073 ± 17.457
Week 63-21.587 ± 9.680-21.753 ± 16.663
Week 65-20.400 ± 9.866-20.950 ± 19.833
Week 67-22.680 ± 10.317-20.150 ± 20.250
Week 69-21.279 ± 9.423-17.827 ± 22.194
Week 71-19.008 ± 8.255-20.585 ± 21.125
Week 73-23.058 ± 7.766-20.080 ± 17.803
Week 75-21.492 ± 7.453-20.771 ± 20.261
Week 77-23.267 ± 8.972-19.814 ± 19.337
Week 79-21.125 ± 12.701-21.027 ± 19.830
Week 81-19.255 ± 9.478-22.331 ± 20.117
Week 83-16.567 ± 12.565-25.091 ± 13.838
Week 85-18.045 ± 12.183-23.292 ± 12.976
Week 87-19.990 ± 12.043-21.473 ± 14.444
Week 89-17.790 ± 11.036-24.782 ± 13.390
Week 91-16.944 ± 13.476-23.091 ± 14.949
Week 93-18.300 ± 11.132-24.970 ± 13.852
Week 95-18.613 ± 12.265-23.564 ± 11.122
Week 97-18.656 ± 11.462-26.122 ± 11.870
Week 99-17.389 ± 10.932-23.700 ± 12.919
Week 101-18.411 ± 10.175-25.940 ± 12.309
Week 103-18.178 ± 11.156-22.655 ± 11.308
Week 105-19.422 ± 8.444-26.920 ± 10.996
Week 107-18.100 ± 9.955-23.018 ± 12.755
Week 109-18.456 ± 10.606-25.422 ± 14.100
Week 111-19.767 ± 9.992-24.380 ± 12.298
Week 113-19.389 ± 9.192-23.940 ± 15.514
Week 115-19.622 ± 8.194-21.533 ± 14.215
Week 117-22.088 ± 10.247-22.225 ± 15.256
Week 119-20.038 ± 8.529-22.713 ± 14.859
Week 121-22.063 ± 7.215-21.183 ± 10.750
Week 123-21.438 ± 8.058-22.029 ± 12.421
Week 125-20.657 ± 8.889-19.560 ± 12.997
Week 127-20.550 ± 9.782-21.433 ± 15.850
Week 129-22.883 ± 11.291-19.020 ± 11.749
Week 131-19.420 ± 12.936-23.100 ± 15.797
Week 133-27.600 ± 7.477-17.450 ± 16.917
Week 135-29.500 ± 7.816-21.900 ± 19.552
Week 137-28.833 ± 8.615-11.650 ± 18.173
Week 139-25.800 ± 9.081-24.733 ± 17.470
Week 141-34.400 ± 2.404-13.833 ± 16.669
Week 143-26.967 ± 9.235-20.033 ± 22.861
Week 145-32.900 ± 3.677-18.100 ± 27.217
Week 147-29.300 ± 7.418-3.300 ± 34.083
Week 149-31.700-7.300 ± 28.284
Week 151-21.500 ± 0.5660.300
Week 153-30.800-11.400
Week 155-35.3000.700
Week 157-32.400-0.100
Week 159-32.5004.700
Week 161-36.8005.500
Week 163-37.10013.000
Week 165-36.300—
Week 167-34.300—
Week 169-32.700—
Week 171-33.100—
Week 173-32.100—
Week 175-28.400—
ET/SFU Visit1.976 ± 9.4441.165 ± 18.773
SecondaryPart B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Each Specified Time Points

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 were added to obtain a total score. The Total score ranged from 0 to 52, with higher score indicating more fatigue. Baseline (Week 0) was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184).

Time frame:
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)
Reported as:
Mean · score on a scale
Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Each Specified Time Points
score on a scaleBIVV009/BIVV009Placebo/BIVV009
Week 3911.048 ± 12.3337.958 ± 12.003
Week 5110.080 ± 11.5066.354 ± 9.680
Week 6310.672 ± 13.2258.499 ± 11.146
Week 759.861 ± 12.95310.304 ± 9.722
Week 8711.015 ± 13.9728.483 ± 11.323
Week 9912.109 ± 14.7868.788 ± 10.985
Week 11111.563 ± 13.41110.688 ± 11.768
Week 12310.806 ± 13.7366.583 ± 16.613
Week 13516.683 ± 18.95312.650 ± 15.243
Week 1479.208 ± 1.1200.500 ± 2.121
Week 15920.00010.000
Week 17115.000—
ET/SFU Visit-1.257 ± 10.399-1.551 ± 12.840
SecondaryPart 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

SF-12: 12 item-questionnaire assessed health-related quality of life (HRQOL), contained 12 items, categorized into 8 domains (subscales) of functioning and well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality and social functioning, with each domain score ranged from 0 (poor health) to 100 (better health). Higher scores = good health condition. These 8 domains were further summarized into 2 summary scores, PCS and MCS that ranged from 0 (poor health) to 100 (better health). Higher scores = better HRQOL. Baseline (Week 0): last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit: 9 weeks after administration of last dose (i.e., up to Week 184).

Time frame:
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)
Reported as:
Mean · score on a scale
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
score on a scaleBIVV009/BIVV009Placebo/BIVV009
Week 39-PCS4.814 ± 8.8306.745 ± 11.255
Week 39-MCS8.543 ± 9.1551.151 ± 11.591
Week 51-PCS5.320 ± 6.9135.654 ± 8.527
Week 51-MCS8.461 ± 6.7541.704 ± 8.813
Week 63-PCS5.840 ± 6.9166.216 ± 9.514
Week 63-MCS8.117 ± 9.9551.722 ± 10.175
Week 75-PCS5.723 ± 7.5637.661 ± 10.418
Week 75-MCS7.932 ± 9.2793.519 ± 7.891
Week 87-PCS5.226 ± 8.1968.778 ± 12.405
Week 87-MCS6.058 ± 10.9812.219 ± 9.111
Week 99-PCS3.945 ± 7.4638.262 ± 12.534
Week 99-MCS7.136 ± 11.8504.682 ± 7.698
Week 111-PCS4.800 ± 7.9858.080 ± 12.302
Week 111-MCS8.705 ± 7.7774.411 ± 10.249
Week 123-PCS4.147 ± 7.1107.973 ± 13.200
Week 123-MCS8.650 ± 8.323-2.538 ± 13.136
Week 135-PCS6.660 ± 9.0966.070 ± 13.819
Week 135-MCS8.860 ± 9.8172.790 ± 6.170
Week 147-PCS-1.655 ± 3.769-3.740 ± 1.824
Week 147-MCS11.220 ± 6.095-1.110 ± 0.679
Week 159-PCS5.620-10.410
Week 159-MCS16.4009.590
Week 171-PCS11.980—
Week 171-MCS0.250—
ET/SFU Visit-PCS-3.478 ± 10.875-0.429 ± 10.922
ET/SFU Visit-MCS1.835 ± 11.882-2.137 ± 10.148
SecondaryPart 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

EQ-5D-5L included 2 components: health state utility index (descriptive system) and Visual Analog Scale (VAS). EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response option: no problem, slight problem, moderate problem, severe problem and extreme problems measured with Likert scale. EQ-5D-5L responses converted into single index utility score between 0 to 1. Higher score=better health. EQ-5D-5L VAS rated participant's current health state on scale from 0 (worst imaginable health) to 100 (best imaginable health). Baseline (Week 0): last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit: 9 weeks after administration of last dose (i.e., up to Week 184).

Time frame:
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)
Reported as:
Mean · score on a scale
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
score on a scaleBIVV009/BIVV009Placebo/BIVV009
Week 39-Index score0.020 ± 0.1650.054 ± 0.135
Week 51-Index score0.075 ± 0.173-0.008 ± 0.197
Week 63-Index score0.060 ± 0.2140.015 ± 0.157
Week 75-Index score-0.004 ± 0.1440.063 ± 0.152
Week 87-Index score-0.034 ± 0.2400.059 ± 0.158
Week 99-Index score-0.058 ± 0.2160.058 ± 0.146
Week 111-Index score-0.033 ± 0.2050.050 ± 0.194
Week 123-Index score-0.020 ± 0.2350.031 ± 0.221
Week 135-Index score0.008 ± 0.3510.094 ± 0.245
Week 147-Index score0.054 ± 0.037-0.087 ± 0.222
Week 159-Index score0.1740.087
Week 171-Index score0.053—
ET/SFU Visit-Index score-0.108 ± 0.238-0.077 ± 0.169
Week 39-VAS20.647 ± 16.87112.000 ± 17.146
Week 51-VAS14.800 ± 27.5899.125 ± 21.112
Week 63-VAS19.867 ± 21.60314.375 ± 15.573
Week 75-VAS16.846 ± 22.12018.933 ± 20.243
Week 87-VAS14.077 ± 25.22116.867 ± 17.912
Week 99-VAS19.364 ± 20.79618.385 ± 20.706
Week 111-VAS18.273 ± 19.46322.833 ± 20.621
Week 123-VAS21.667 ± 18.37118.000 ± 30.389
Week 135-VAS26.000 ± 20.43323.400 ± 27.574
Week 147-VAS17.500 ± 17.6783.500 ± 26.163
Week 159-VAS40.00027.000
Week 171-VAS35.000—
ET/SFU Visit-VAS1.526 ± 17.976-2.056 ± 14.957
SecondaryPart B: Number of Participants With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Each Specified Time Points

The PGIS is a self-reported scale. The PGIS is a 1-item questionnaire designed to assess participant's impression of disease severity using a 5-point scale ranging from 1 to 5, where 1=none, 2=mild, 3=moderate, 4=severe, 5=very severe. Higher scores indicated greater severity. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184).

Time frame:
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)
Reported as:
Count of participants · Participants
Part B: Number of Participants With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Each Specified Time Points
ParticipantsBIVV009/BIVV009Placebo/BIVV009
Week 39 - None75
Week 39 - Mild87
Week 39 - Moderate15
Week 39 - Severe10
Week 39 - Very Severe00
Week 51 - None54
Week 51 - Mild87
Week 51 - Moderate25
Week 51 - Severe00
Week 51 - Very Severe00
Week 63 - None64
Week 63 - Mild87
Week 63 - Moderate35
Week 63 - Severe00
Week 63 - Very Severe00
Week 75 - None56
Week 75 - Mild66
Week 75 - Moderate23
Week 75 - Severe00
Week 75 - Very Severe00
Week 87 - None67
Week 87 - Mild54
Week 87 - Moderate13
Week 87 - Severe11
Week 87 - Very Severe00
Week 99 - None58
Week 99 - Mild53
Week 99 - Moderate12
Week 99 - Severe00
Week 99 - Very Severe00
Week 111 - None57
Week 111 - Mild43
Week 111 - Moderate22
Week 111 - Severe00
Week 111 - Very Severe00
Week 123 - None25
Week 123 - Mild62
Week 123 - Moderate12
Week 123 - Severe00
Week 123 - Very Severe00
Week 135 - None02
Week 135 - Mild31
Week 135 - Moderate22
Week 135 - Severe00
Week 135 - Very Severe00
Week 147 - None01
Week 147 - Mild10
Week 147 - Moderate11
Week 147 - Severe00
Week 147 - Very Severe00
Week 159 - None00
Week 159 - Mild00
Week 159 - Moderate11
Week 159 - Severe00
Week 159 - Very Severe00
Week 171 - None00
Week 171 - Mild10
Week 171 - Moderate00
Week 171 - Severe00
Week 171 - Very Severe00
ET/SFU - None24
ET/SFU - Mild53
ET/SFU - Moderate75
ET/SFU - Severe35
ET/SFU - Very Severe21
SecondaryPart B: Number of Participants With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Each Specified Time Points

PGIC is a self-administered questionnaire to evaluate the improvement or worsening compared to the start of the study. PGIC was assessed on a 7-point Likert scale ranged from 1 (greatly improved) to 7 (greatly worsened). Categories were defined based on the PGIC scores as follows: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse and 7=very much worsen. Higher scores indicated greater severity. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184).

Time frame:
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)
Reported as:
Count of participants · Participants
Part B: Number of Participants With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Each Specified Time Points
ParticipantsBIVV009/BIVV009Placebo/BIVV009
Week 39 - Very much improved43
Week 39 - Much improved86
Week 39 - Minimally improved26
Week 39 - No Change21
Week 39 - Minimally worse10
Week 39 - Much worse00
Week 39 - Very much worse00
Week 51 - Very much improved53
Week 51 - Much improved36
Week 51 - Minimally improved24
Week 51 - No Change52
Week 51 - Minimally worse00
Week 51 - Much worse01
Week 51 - Very much worse00
Week 63 - Very much improved53
Week 63 - Much improved84
Week 63 - Minimally improved05
Week 63 - No change43
Week 63 - Minimally worse00
Week 63 - Much worse01
Week 63 - Very much worse00
Week 75 - Very much improved66
Week 75 - Much improved23
Week 75 - Minimally improved15
Week 75 - No Change41
Week 75 - Minimally worse00
Week 75 - Much worse00
Week 75 - Very much worse00
Week 87 - Very much improved77
Week 87 - Much improved03
Week 87 - Minimally improved21
Week 87 - No Change23
Week 87 - Minimally worse11
Week 87 - Much worse10
Week 87 - Very much worse00
Week 99 - Very much improved38
Week 99 - Much improved32
Week 99 - Minimally improved13
Week 99 - No change30
Week 99 - Minimally worse10
Week 99 - Much worse00
Week 99 - Very much worse00
Week 111 - Very much improved36
Week 111 - Much improved54
Week 111 - Minimally improved11
Week 111 - No Change21
Week 111 - Minimally worse00
Week 111 - Much worse00
Week 111 - Very much worse00
Week 123 - Very much improved34
Week 123 - Much improved33
Week 123 - Minimally improved21
Week 123 - No Change11
Week 123 - Minimally worse00
Week 123 - Much worse00
Week 123 - Very much worse00
Week 135 - Very much improved22
Week 135 - Much improved21
Week 135 - Minimally improved01
Week 135 - No Change01
Week 135 - Minimally worse10
Week 135 - Much worse00
Week 135 - Very much worse00
Week 147 - Very much improved10
Week 147 - Much improved01
Week 147 - Minimally improved01
Week 147 - No Change10
Week 147 - Minimally worse00
Week 147 - Much worse00
Week 147 - Very much worse00
Week 159 - Very much improved10
Week 159 - Much improved00
Week 159 - Minimally improved01
Week 159 - No Change00
Week 159 - Minimally worse00
Week 159 - Much worse00
Week 159 - Very much worse00
Week 171- Very much improved10
Week 171- Much improved00
Week 171- Minimally improved00
Week 171- No Change00
Week 171- Minimally worse00
Week 171- Much worse00
Week 171- Very much worse00
ET/SFU Visit- Very much improved33
ET/SFU Visit- Much improved56
ET/SFU Visit- Minimally improved41
ET/SFU Visit- No Change33
ET/SFU Visit- Minimally worse12
ET/SFU Visit- Much worse33
ET/SFU Visit- Very much worse00
SecondaryPart B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points

Change from baseline (Week 0) in LDH levels at each specified time points (i.e., Week 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, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107,109, 111, 113, 115, 117, 119, 121,123, 125, 127,129,131,133,135,137,139,141,143,145,147, 149, 151,153,155,157,159,161,163,165,167,169, 171, 173, 175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184).

Time frame:
Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
Reported as:
Mean · units per liter
Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points
units per literBIVV009/BIVV009Placebo/BIVV009
Week 27-151.000 ± 184.6400.650 ± 208.051
Week 29-115.944 ± 226.91311.000 ± 222.383
Week 31-85.111 ± 247.50638.882 ± 211.386
Week 33-66.176 ± 324.1454.813 ± 203.939
Week 35-64.667 ± 261.431-19.313 ± 142.989
Week 374.438 ± 398.84325.765 ± 219.679
Week 39-88.500 ± 271.94127.313 ± 210.705
Week 4123.778 ± 342.195-6.000 ± 173.810
Week 43-22.118 ± 310.381-21.706 ± 181.668
Week 4526.529 ± 329.717-13.500 ± 190.460
Week 47-22.600 ± 302.511-24.944 ± 153.580
Week 49-29.250 ± 289.39215.722 ± 193.630
Week 51-12.563 ± 290.489-9.556 ± 155.646
Week 53-16.938 ± 299.78812.529 ± 206.642
Week 55-89.500 ± 219.634-11.250 ± 177.647
Week 57-78.200 ± 285.14064.188 ± 266.395
Week 59-84.438 ± 220.37631.647 ± 226.128
Week 61-74.353 ± 215.41420.588 ± 263.984
Week 63-98.235 ± 185.25938.059 ± 325.329
Week 65-97.438 ± 212.335-16.467 ± 246.765
Week 67-127.824 ± 192.14829.667 ± 269.918
Week 69-113.625 ± 197.27036.563 ± 303.550
Week 71-101.692 ± 320.3484.067 ± 307.924
Week 73-174.500 ± 177.1537.063 ± 245.723
Week 75-157.429 ± 184.5257.067 ± 285.183
Week 77-142.857 ± 199.169-24.867 ± 291.754
Week 79-98.077 ± 271.632-20.063 ± 265.761
Week 81-127.846 ± 233.6637.200 ± 219.952
Week 83-59.000 ± 346.9178.818 ± 250.068
Week 85-72.000 ± 350.02128.400 ± 282.626
Week 87-101.385 ± 285.59083.385 ± 288.731
Week 89-78.667 ± 351.05910.833 ± 323.647
Week 91-143.000 ± 273.5400.846 ± 288.451
Week 93-133.500 ± 254.33210.818 ± 268.308
Week 95-59.364 ± 368.70818.231 ± 241.354
Week 97-53.364 ± 343.820-38.500 ± 188.403
Week 99-80.909 ± 312.405-12.917 ± 183.844
Week 101-90.273 ± 293.680-17.182 ± 249.134
Week 103-50.273 ± 331.0725.692 ± 211.233
Week 105-96.455 ± 276.907-34.250 ± 147.738
Week 107-28.091 ± 354.24420.769 ± 222.772
Week 109-50.727 ± 335.078-2.000 ± 243.243
Week 111-83.000 ± 303.258-5.583 ± 219.850
Week 113-80.700 ± 319.2830.667 ± 294.904
Week 115-109.500 ± 256.39544.700 ± 295.946
Week 117-140.444 ± 280.94412.700 ± 254.786
Week 119-149.556 ± 237.771-26.500 ± 274.168
Week 121-195.778 ± 225.978-42.375 ± 211.840
Week 123-185.000 ± 231.48922.222 ± 278.037
Week 125-99.429 ± 285.513-85.143 ± 265.374
Week 127-154.714 ± 231.922-28.875 ± 312.483
Week 129-136.429 ± 234.954-18.571 ± 354.584
Week 131-120.833 ± 300.454-2.000 ± 270.245
Week 133-179.000 ± 298.811-47.500 ± 367.639
Week 135-211.800 ± 265.43858.000 ± 449.233
Week 137-252.500 ± 264.59146.500 ± 768.625
Week 139-181.800 ± 284.966-48.667 ± 373.339
Week 141-259.667 ± 362.13630.667 ± 372.889
Week 143-160.250 ± 357.021-7.500 ± 21.920
Week 145-340.500 ± 458.912290.000 ± 562.857
Week 147-248.667 ± 355.136311.000 ± 547.301
Week 149-78.000116.000 ± 175.362
Week 15158.000 ± 32.527295.000
Week 1537.00075.000
Week 155-50.000—
Week 157-50.000369.000
Week 159-155.000365.000
Week 161-175.000—
Week 163-149.000782.000
Week 165-155.000—
Week 167-162.000—
Week 169-180.000—
Week 171-167.000—
Week 173-171.000—
Week 175-121.000—
ET/SFU Visit-2.500 ± 195.967-11.706 ± 206.321
SecondaryPart B: Number of Blood Transfusions Per Participant

A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was \<9 g/dL and the participant had symptoms of anemia or Hgb was \<7 g/dL and the participant was asymptomatic.

Time frame:
From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
Reported as:
Mean · blood transfusions per participant
Part B: Number of Blood Transfusions Per Participant
blood transfusions per participantBIVV009/BIVV009Placebo/BIVV009
Part B: Number of Blood Transfusions Per Participant0.4 ± 0.80.3 ± 0.4
SecondaryPart B: Mean Change From Baseline in Haptoglobin Values at Each Specified Time Points

Change from baseline (Week 0) in haptoglobin values at each specified time points (i.e., Week 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, 81, 83, 85, 87, 89, 91, 93, 95, 97,99,101,103, 105, 107,109, 111,113,115,117,119, 121,123, 125, 127, 129,131,133,135,137,139,141,143, 145,147,149,151,153,155,157,159, 161,163,165,167,169,171,173,175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 184). Haptoglobin values \<0.2 were imputed as 0.2.

Time frame:
Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184)
Reported as:
Mean · grams per liter
Part B: Mean Change From Baseline in Haptoglobin Values at Each Specified Time Points
grams per literBIVV009/BIVV009Placebo/BIVV009
Week 270.219 ± 0.3800.082 ± 0.197
Week 290.240 ± 0.3170.182 ± 0.482
Week 310.183 ± 0.3110.256 ± 0.516
Week 330.212 ± 0.4230.229 ± 0.379
Week 350.207 ± 0.3550.151 ± 0.280
Week 370.232 ± 0.4190.187 ± 0.291
Week 390.213 ± 0.3300.165 ± 0.295
Week 410.119 ± 0.2380.082 ± 0.168
Week 430.100 ± 0.2240.161 ± 0.234
Week 450.114 ± 0.2050.189 ± 0.275
Week 470.135 ± 0.2430.255 ± 0.416
Week 490.139 ± 0.2050.172 ± 0.345
Week 510.083 ± 0.1970.207 ± 0.369
Week 530.045 ± 0.1370.122 ± 0.296
Week 550.149 ± 0.2510.179 ± 0.343
Week 570.158 ± 0.2340.158 ± 0.362
Week 590.132 ± 0.2290.131 ± 0.306
Week 610.153 ± 0.2860.184 ± 0.350
Week 630.202 ± 0.2650.177 ± 0.357
Week 650.101 ± 0.2320.198 ± 0.384
Week 670.178 ± 0.2410.162 ± 0.363
Week 690.168 ± 0.2550.169 ± 0.348
Week 710.220 ± 0.2880.236 ± 0.388
Week 730.261 ± 0.3350.174 ± 0.348
Week 750.275 ± 0.3210.197 ± 0.362
Week 770.249 ± 0.3740.232 ± 0.398
Week 790.299 ± 0.4190.290 ± 0.464
Week 810.438 ± 0.4630.207 ± 0.421
Week 830.297 ± 0.3790.233 ± 0.394
Week 850.374 ± 0.3740.266 ± 0.426
Week 870.334 ± 0.4090.344 ± 0.471
Week 890.348 ± 0.4820.198 ± 0.351
Week 910.313 ± 0.4490.279 ± 0.449
Week 930.262 ± 0.3830.178 ± 0.373
Week 950.263 ± 0.4950.198 ± 0.414
Week 970.245 ± 0.3060.210 ± 0.407
Week 990.266 ± 0.3510.213 ± 0.370
Week 1010.289 ± 0.2890.207 ± 0.417
Week 1030.219 ± 0.2910.212 ± 0.389
Week 1050.216 ± 0.2910.174 ± 0.399
Week 1070.182 ± 0.2730.245 ± 0.459
Week 1090.207 ± 0.3110.254 ± 0.507
Week 1110.282 ± 0.5560.263 ± 0.459
Week 1130.248 ± 0.3660.335 ± 0.614
Week 1150.324 ± 0.4130.165 ± 0.432
Week 1170.450 ± 0.4920.181 ± 0.489
Week 1190.348 ± 0.4000.187 ± 0.404
Week 1210.459 ± 0.4140.174 ± 0.479
Week 1230.350 ± 0.3750.192 ± 0.512
Week 1250.303 ± 0.4250.114 ± 0.298
Week 1270.309 ± 0.4010.220 ± 0.420
Week 1290.393 ± 0.5060.191 ± 0.506
Week 1310.480 ± 0.5290.222 ± 0.430
Week 1330.342 ± 0.4690.125 ± 0.155
Week 1350.454 ± 0.6430.280 ± 0.425
Week 1370.545 ± 0.6310.070 ± 0.121
Week 1390.494 ± 0.6760.293 ± 0.508
Week 1410.667 ± 0.5830.025 ± 0.035
Week 1430.513 ± 0.6040.270 ± 0.292
Week 1450.580 ± 0.8200.130 ± 0.141
Week 1470.400 ± 0.5920.195 ± 0.276
Week 1490.0000.000 ± 0.000
Week 1510.000 ± 0.0000.000
Week 1530.0000.000
Week 1550.0000.000
Week 1570.0000.000
Week 1590.0000.000
Week 1610.1800.000
Week 1630.0000.000
Week 1650.000—
Week 1670.000—
Week 1690.000—
Week 1710.000—
Week 1730.000—
Week 1750.000—
ET/SFU Visit0.055 ± 0.2000.181 ± 0.426
SecondaryPart B: Number of Healthcare Visits by Type

In this outcome measure, number of healthcare visits which included non-study healthcare resource utilization visit (consisted mainly of extra visits to the office of the study doctor, visit to a generalist doctor or visit to a specialist doctor), hospitalization visit and visit to hospital emergency is reported.

Time frame:
From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
Reported as:
Number · visits
Part B: Number of Healthcare Visits by Type
visitsBIVV009/BIVV009Placebo/BIVV009
Non-study healthcare resource utilization visits1312
Hospitalization31
Visit to a hospital emergency room13

Adverse events

Collected over Part A (both 6.5 g and 7.5 g cohorts): first dose (Day 0) up to Week 25; 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). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A: BIVV009 6.5 g0/17 (0%)2/17 (11.8%)16/17 (94.1%)
Part A: BIVV009 7.5 g0/5 (0%)1/5 (20%)5/5 (100%)
Part A: Placebo0/20 (0%)0/20 (0%)3/20 (15%)
Part B: BIVV009 6.5 g1/32 (3.1%)6/32 (18.8%)28/32 (87.5%)
Part B: BIVV009 7.5 g0/7 (0%)1/7 (14.3%)7/7 (100%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventPart A: BIVV009 6.5 gPart A: BIVV009 7.5 gPart A: PlaceboPart B: BIVV009 6.5 gPart B: BIVV009 7.5 g
Febrile InfectionInfections and infestations0/171/50/200/320/7
Blood Immunoglobulin M IncreasedInvestigations0/171/50/200/320/7
Urinary Tract InfectionInfections and infestations0/170/50/200/321/7
Lumbar Spinal StenosisMusculoskeletal and connective tissue disorders0/170/50/200/321/7
OsteoarthritisMusculoskeletal and connective tissue disorders0/170/50/201/321/7
Cerebral Venous Sinus ThrombosisNervous system disorders1/170/50/200/320/7
Raynaud's PhenomenonVascular disorders1/170/50/200/320/7
AnaemiaBlood and lymphatic system disorders0/170/50/201/320/7
Polycystic Liver DiseaseCongenital, familial and genetic disorders0/170/50/201/320/7
CholelithiasisHepatobiliary disorders0/170/50/201/320/7
Most frequent other events
Showing 10 of 141
Most frequent other events
EventPart A: BIVV009 6.5 gPart A: BIVV009 7.5 gPart A: PlaceboPart B: BIVV009 6.5 gPart B: BIVV009 7.5 g
FatigueGeneral disorders1/171/50/207/325/7
DyspnoeaRespiratory, thoracic and mediastinal disorders0/172/50/202/323/7
AnaemiaBlood and lymphatic system disorders0/172/50/209/322/7
NasopharyngitisInfections and infestations0/172/50/205/322/7
PalpitationsCardiac disorders0/170/50/201/322/7
NauseaGastrointestinal disorders1/170/50/203/322/7
AstheniaGeneral disorders0/171/50/204/322/7
CystitisInfections and infestations0/170/50/202/322/7
ArthralgiaMusculoskeletal and connective tissue disorders2/171/51/206/322/7
DizzinessNervous system disorders2/170/50/203/322/7

Baseline characteristics

Analysis was performed on full analysis set (FAS) which included all randomized participants who received at least 1 dose (including partial dose) of study drug (BIVV009 or placebo).

Age, Continuous
Age, Continuous(years)BIVV009/BIVV009Placebo/BIVV009Total
Mean65.3 ± 10.968.2 ± 10.166.7 ± 10.5
Sex: Female, Male
Sex: Female, Male(Participants)BIVV009/BIVV009Placebo/BIVV009Total
Female171633
Male549
Race (NIH/OMB)
Race (NIH/OMB)(Participants)BIVV009/BIVV009Placebo/BIVV009Total
American Indian or Alaska Native000
Asian527
Native Hawaiian or Other Pacific Islander000
Black or African American000
White044
More than one race000
Unknown or Not Reported171431
07

Study locations

53 sites
  • Arizona Oncology Associates PC
    Tucson, Arizona 85711, United States
  • USC/Keck School of Medicine
    Los Angeles, California 90033, United States
  • Georgetown University Medical Center
    Georgetown, District of Columbia 20007, United States
  • Cleveland Clinic Florida
    Weston, Florida 33331, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Brigham and Women's Hospital
    Boston, Massachusetts 02115, United States
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
  • Montefiore Medical Center
    New York, New York 10461, United States
  • New York Medical College at Westchester Medical Center
    Valhalla, New York 10595, United States
  • East Carolina University
    Greenville, North Carolina 27834, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • Hospital of the University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • University of Pittsburgh Medical Center
    Pittsburgh, Pennsylvania 15232, United States
  • UW Hospitals and Clinics
    Madison, Wisconsin 53792, United States
  • USC Health Clinics
    Buderim, Queensland 4556, Australia
  • Ballarat Oncology & Haematology
    Ballarat, Victoria 3350, Australia
  • Monash Medical Centre
    Clayton, Victoria 3168, Australia
  • Perth Blood Institute
    West Perth, Western Australia 6005, Australia
  • Medical University of Vienna
    Vienna, 1090, Austria
  • ZNA Stuivenberg
    Antwerpen, 2060, Belgium
  • University Hospitals Leuven
    Leuven, 3000, Belgium
  • St. Michael's Hospital
    Toronto, Ontario M5B1W8, Canada
  • McGill University Health Center
    Montréal, Quebec H4A3J1, Canada
  • CHU d'Angers
    Angers Cedex 9, 49933, France
  • Hôpital de Caen
    Caen, 14033, France
  • Centre Hospitalier Henri Mondor
    Créteil, 94000, France
  • Centre Hospitalier Lyon Sud
    Pierre-Bénite, 69495, France
  • Gemeinschaftspraxis Hämatologie-Onkologie
    Dresden, 1307, Germany
  • Universitätsklinikum Essen
    Essen, 45147, Germany
  • Univ Ulm, Inst Klin. Transfusions. Immungen
    Ulm, 89081, Germany
  • Hadassah Medical Center
    Jerusalem, 91120, Israel
  • Laniado Hospital
    Netanya, 4244916, Israel
  • A. O. Spedali Civili di Brescia
    Brescia, 25123, Italy
  • Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
    Milan, 20122, Italy
  • U.O.C. Ematologia- Policlinico "A. Gemelli"
    Rome, 00168, Italy
  • U.O.C. Ematologia Ospedale San Bortolo
    Vicenza, 36100, Italy
  • Japanese Red Cross Society Himeji Hospital
    Himeji, Hyogo 670-8540, Japan
  • Ishikawa Prefectural Central Hospital
    Kanazawa, Ishikawa-ken 9208530, Japan
  • Tokai University Hospital
    Isehara, Kanagawa 259-1193, Japan
  • Osaka University Hospital
    Suita, Osaka 565-0871, Japan
  • Saitama Medical University Hospital
    Iruma-gun, Saitama-Ken 350-0495, Japan
  • Aichi Medical University Hospital
    Nagakute, 480-1195, Japan
  • Academisch Medisch Centrum
    Amsterdam, 1105, Netherlands
  • Leids Universitair Medisch Centrum
    Leiden, 2333, Netherlands
  • Haukeland University Hospital
    Bergen, 5053, Norway
  • St Olavs Hospital, Avdeling for blodsykdommer
    Trondheim, 7030, Norway
  • Hospital Universitario Puerta de Hierro
    Majadahonda, Madrid 28222, Spain
  • Hospital Clinci i Provincial de Barcelona
    Barcelona, 08036, Spain
  • Hospital Universitario Virgen del Rocio
    Sevilla, 41013, Spain
  • Hospital Universitario Dr. Peset
    Valencia, 46017, Spain
  • St James Hospital, Leeds
    Leeds, LS9 7TF, United Kingdom
  • Imperial College Healthcare NHS Trust, Hammersmith Hospital
    London, W12 0HS, United Kingdom
  • University College London
    London, WC1E 6AG, United Kingdom
08

References and documents

Publications

  • Roth A, Berentsen S, Barcellini W, D'Sa S, Jilma B, Michel M, Weitz IC, Yamaguchi M, Nishimura JI, Vos JMI, Storek M, Wong N, Patel P, Jiang X, Vagge DS, Wardecki M, Shafer F, Lee M, Broome CM. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial. Blood. 2022 Sep 1;140(9):980-991. doi: 10.1182/blood.2021014955. PubMed 35687757 ↗

Study documents

  • Study protocol · Nov 4, 2020
  • Statistical analysis plan · Oct 2, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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

09

Registry details

Key details

Study ID
NCT03347422
Lead sponsor
Bioverativ, a Sanofi company
Responsible party
Sponsor
First posted
Nov 20, 2017
Start date
Mar 17, 2018
Primary completion
Dec 3, 2021
Completion
Dec 3, 2021
Results posted
Dec 23, 2022
Last update
Dec 23, 2022

Study contacts

Clinical Sciences & Operations
study director · Sanofi

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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