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)

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

Mean change from baseline in bilirubin levels at the treatment assessment timepoint was 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, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at 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 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, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

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

Mean change from baseline 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. LS mean and 95% CI was assessed by MMRM approach using 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, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

Part A: 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. Number of transfusions after the first 5 weeks of study drug administration and up to Week 26 are reported in this outcome measure.

Time frame: From Week 5 up to Week 26

Part A: Number of Blood Units Transfused 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. Number of blood units transfused after the first 5 weeks of study drug administration and up to Week 26 are reported in this outcome measure.

Time frame: From Week 5 up to Week 26

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

Mean change from baseline (Week 0) in Hgb at 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. LS mean and 95% CI was assessed by MMRM approach using 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, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)

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

Change From Hgb level from baseline (Week 0) at each specified time points (i.e., 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 and early termination/safety follow up \[ET/SFU\] 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 185).

Time frame: 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)

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

Change from baseline (Week 0) in bilirubin levels at each specified time point (i.e., 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 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 185).

Time frame: 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)

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

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 185).

Time frame: 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)

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 for which, score ranged 0 (poor health) to 100 (better health). Higher scores = better HRQOL. Baseline (Week 0) was defined as the last non-missing value prior to 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 185). Change from baseline in SF-12 PCS and MCS scores is reported in this outcome measure.

Time frame: Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135 and ET Visit/SFU visit (i.e., up to Week 185)

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

EQ-5D-5L:standardized, participant-rated questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L 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 problems, slight problems, moderate problems, severe problems, and extreme problems measured with Likert scale. EQ-5D-5L responses relating to 5 dimensions are converted into a single index utility score between 0 to 1, where higher score=better health state. The EQ-5D-5L VAS rated participant's current health state on a scale from 0=worst imaginable health state to 100 =best imaginable health state. Baseline (Week 0): last non-missing value prior to 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 185).

Time frame: 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)

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

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 185).

Time frame: 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)

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

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 185).

Time frame: 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)

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

Mean change from baseline in LDH levels at each specified time points (i.e., 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 and ET/SFU Visit) is reported in this outcome measure. 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 185).

Time frame: 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)

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)

Part B: Number of Blood Units Transfused 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)

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

Change in Haptoglobin values from baseline at each specified time points (i.e., 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 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 185). Haptoglobin values \<0.2 were imputed as 0.2.

Time frame: 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)

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, or visit to a generalist doctor, or visit to a specialist doctor) and 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)