A Study to Determine the Efficacy and Safety of Luspaterc... | NCT03342404

ID	Type	Description	Link
U1111-1202-7068	Registry Identifier	WHO
2015-003225-33	EudraCT Number

Name	Class
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA	INDUSTRY

Description Module

Detailed Description

The primary objective is:

- To evaluate the effect of luspatercept (BMS-986346) versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval, from Week 13 to Week 24, compared to baseline.

The secondary objectives are:

To evaluate the effect of luspatercept versus placebo in anemia-related symptoms in participants with β-thalassemia, as measured by non-transfusion dependent β-thalassemia-patient reported outcome (NTDT-PRO) over continuous 12-week intervals (from Weeks 13 to 24 and from Weeks 37 to 48) compared to baseline.
To evaluate the effect of luspatercept versus placebo on functional and health-related quality of life (QoL) as measured by Medical Outcomes Study 36-Item Short Form (SF-36) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaires
To evaluate the long-term effect of luspatercept versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval from Week 37 to Week 48, compared to baseline
To evaluate the effect of luspatercept versus placebo on iron overload, as measured by liver iron concentration (LIC) and iron chelation therapy (ICT) daily dose
To evaluate the effect of luspatercept versus placebo on iron overload, as measured by serum ferritin
To evaluate the duration of erythroid response
To evaluate the effect of luspatercept versus placebo on physical activity measured by 6-minute walk test (6MWT)

Safety and Pharmacokinetics (PK) Objectives

To evaluate safety and tolerability of luspatercept, including immunogenicity
To evaluate population pharmacokinetics (PK) of luspatercept in subjects with β-thalassemia

The exploratory objectives are:

To evaluate the effect of luspatercept versus placebo on measures of extra-medullary hematopoietic (EMH) masses, bone mineral density, splenomegaly, pulmonary hypertension, and leg ulcers, when present
To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the NTDT severity score system
To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the Morbidity-free Survival parameters
To examine the relationship of baseline and change in serum Growth Differentiation Factor 11 (GDF11) and other related biomarkers with response to treatment with luspatercept
To examine the effect of luspatercept on fetal hemoglobin (HbF)
To examine the effect of luspatercept on Health Resource Utilization (HRU)

Label	Type	Description	Intervention Names
Luspatercept (ACE-536) plus Best Supportive Care (BSC)	Experimental	Arm Description: Luspatercept, subcutaneous(ly) (SC) once every 21 days	Drug: Luspatercept Other: Best Supportive Care (BSC)
Placebo plus Best Supportive Care (BSC)	Placebo Comparator	normal saline solution subcutaneous(ly) (SC) once every 21 days	Other: Placebo Other: Best Supportive Care (BSC)

Name	Type	Description	Arm Group Labels	Other Names
Luspatercept	Drug	Subjects will start with luspatercept at 1 mg/kg dose level every 3 weeks and can be dose escalated up to 1.25 mg/kg.	Luspatercept (ACE-536) plus Best Supportive Care (BSC)

Measure	Description	Time Frame
Percentage of Participants Achieving Erythroid Response (Week 13 to Week 24)	Erythroid Response is defined as an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Weeks 13 to 24 of treatment in the absence of transfusions. Baseline hemoglobin (Hb) is the average of 2 or more Hb measurements at least 1 week apart within 4 weeks prior to Dose 1.	From Week 13 to Week 24 of study treatment

Measure	Description	Time Frame
Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score (Week 13 to Week 24)	The NTDT-PRO assesses the severity of anemia-related symptoms with a daily recall of symptoms composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Tiredness/Weakness (T/W) domain score is the average score of items 1 through 4 above. T/W domain score ranges from 0 (best outcome, no tiredness/weakness) to 10 (worst outcome, extreme tiredness/weakness). Weekly T/W Scores are the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 13 to Week 24) are compared to the T/W Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

Subjects must be ≥ 18 years of age at the time of signing the informed consent document (ICF).
Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
Subject is willing and able to adhere to the study visit schedule (eg, not scheduled to receive hematopoietic stem cell transplantation) and other protocol requirements.
Subject must have documented diagnosis of β-thalassemia or hemoglobin E/ β-thalassemia. Concomitant alpha globin mutation and/or duplication are allowed.
Subject must be non-transfusion dependent, defined as 0 to 5 units of RBCs received during the 24-week period prior to randomization. Note: 1 unit defined for this entry criterion as approximately 200 to 350 mL of transfused packed RBCs.
Subject must not be on a regular transfusion program and must be RBC transfusion-free for at least ≥ 8 weeks prior to randomization
Subject must have mean baseline hemoglobin ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to randomization; hemoglobin values within 21 days post-transfusion will be excluded.
Subject must have performance status: Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.
A female of childbearing potential (FCBP) for this study is defined as a female who:

1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). A FCBP participating in the study must:

Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact.
Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented). If a FCBP engages in sexual activity that may result in a pregnancy, she must agree to use, and be able to comply during the study therapy (including dose interruptions), and for 12 weeks (approximately 5 times the mean terminal half-life of luspatercept based on multiple dose pharmacokinetics [PK] data) after discontinuation of study therapy.

10. Male subjects must:

a. Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal half-life of luspatercept based on multiple-dose PK data) following IP discontinuation, even if he has undergone a successful vasectomy

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
Any condition that confounds the ability to interpret data from the study.
Diagnosis of hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg,Hemoglobin H).
Active hepatitis C (HCV) infection
Deep vein thrombosis (DVT) or stroke requiring medical intervention ≤ 24 weeks prior to randomization.
Subjects on chronic anticoagulant therapy are excluded, unless they stopped the treatment at least 28 days prior to randomization. Anticoagulant therapies for prophylaxis and for surgery or high-risk procedures as well as low molecular weight (LMW) heparin for superficial vein thrombosis (SVT) and chronic aspirin are allowed before and during the study.
Treatment with another investigational drug or device ≤ 28 days prior to randomization.
Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
Platelet count > 1000 x 109/L.
Subjects on iron chelation therapy (ICT) at the time of ICF signature must have initiated the treatment with ICT at least 24 weeks before the predicted randomization date. ICT can be initiated at any time during treatment and should be used according to the label.
Subject had Hydroxyurea and ESA treatment ≤ 24 weeks prior to randomization, and no prior gene therapy.
Subject is pregnant or a lactating female.
Uncontrolled hypertension. Controlled hypertension for this protocol is considered ≤ Grade 1 according to National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) version 4.0 (current active minor version).
Subject has major organ damage, including:
1. Liver disease with alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN) or history/evidence of cirrhosis, as well as presence of masses/tumor detected by ultrasound at screening.
2. Heart disease, heart failure as classified by the New York Heart Association (NYHA) classification 3 or higher, or significant arrhythmia requiring treatment, or recent myocardial infarction (MI) within 6 months of randomization.
3. Severe lung disease, including pulmonary fibrosis or pulmonary hypertension, ie, ≥G3 NCI CTCAE version 4.0 (current active minor version).
4. Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 (per Modification of Diet in Renal Disease [MDRD] formula).
Subject has received chronic systemic glucocorticoids ≤ 12 weeks prior to randomization (physiologic replacement therapy for adrenal insufficiency is allowed).
Major surgery ≤ 12 weeks prior to randomization (subjects must have completely recovered from any previous surgery prior to randomization).
History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (see Investigator Brochure).
Subject has received immunosuppressants ≤ 28 days prior to randomization.
History or current malignancies (solid tumors and hematological malignancies) unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)

Name	Affiliation	Role
Jeevan Shetty, MD	Celgene Corporation	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital of Los Angeles		Los Angeles	California	90027	United States
Local Institution - 501

PubMed Identifier	Type	Citation	Retractions
30617198	Background	Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7.
41857682

Label	URL
BMS Clinical Trial Information	View source

ID	Title	Description
FG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 12, 2020	Sep 10, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Achieving Erythroid Response (Week 13 to Week 24)

Erythroid Response is defined as an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Weeks 13 to 24 of treatment in the absence of transfusions. Baseline hemoglobin (Hb) is the average of 2 or more Hb measurements at least 1 week apart within 4 weeks prior to Dose 1.

All treated participants. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Number

95% Confidence Interval

Percent of Participants

From Week 13 to Week 24 of study treatment

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Units	Counts
Participants	OG00096 OG00149

Title

Denominators

Categories

Title	Measurements
	OG00077.1(67.4 to 85.0) OG0010.0(0.0 to 7.3)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Difference in proportions	77.1			2-Sided	95	63.4	87.0			The difference in proportions (luspatercept - placebo) and 95% CI were estimated from the exact unconditional test		Superiority
OG000 OG001

Secondary

Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score (Week 13 to Week 24)

The NTDT-PRO assesses the severity of anemia-related symptoms with a daily recall of symptoms composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Tiredness/Weakness (T/W) domain score is the average score of items 1 through 4 above. T/W domain score ranges from 0 (best outcome, no tiredness/weakness) to 10 (worst outcome, extreme tiredness/weakness). Weekly T/W Scores are the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 13 to Week 24) are compared to the T/W Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13.

All treated participants with available measurements at Baseline and from Week 13 to Week 24. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline and over a continuous 12 week period (from week 13 through week 24)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Secondary

Mean Change From Baseline in Hemoglobin Values in the Absence of Transfusion (Week 13 to Week 24)

Mean change from baseline in mean of hemoglobin (Hb) values over a continuous 12-week interval from Week 13 to Week 24 in the absence of transfusions. Baseline was defined as the average of 2 or more Hb measurements at least 1 week apart within 4 weeks before Dose 1 Day 1.

All treated participants with available measurements at Baseline and From Week 13 to Week 24. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Least Squares Mean

Standard Error

g/dL

Baseline and over a continuous 12 week period (from week 13 through week 24)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Percentage of Participants Achieving Erythroid Response (Week 37 to Week 48)

Erythroid Response is defined as an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Weeks 37 to 48 of treatment in the absence of transfusions. Baseline hemoglobin (Hb) is the average of 2 or more Hb measurements at least 1 week apart within 4 weeks prior to Dose 1.

All treated participants. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Number

95% Confidence Interval

Percentage of Participants

Assessed over a continuous 12 week period (from week 37 through week 48)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Mean Change From Baseline in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 13 to Week 24)

The FACIT-F is a multidimensional, self-report quality of life instrument which includes the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire (27 items over 4 different domains), and the Fatigue subscale (FS) component (13 items). FACIT-F version 4 has been used for this study. For the Fatigue subscale, each of the 13 items is scored from 0 ("not at all") to 4 ("very much"). The scores from individual items are summed to generated the final FS score, which ranges from 0 (best outcome) to 52 (worst outcome). The questionnaire is completed every other dose, and the mean of FS scores from Week 13 to Week 24 is compared to the FS score at baseline (last score available before start of study treatment). Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13.

All treated participants with available measurements at Baseline and at least one post-baseline FACIT-F questionnaire completed. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline and over a continuous 12 week period (from week 13 through week 24)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Secondary

Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Shortness of Breath (SoB) Domain Score (Week 13 to Week 24)

The NTDT-PRO V2.1 assess the severity of anemia-related symptoms associated with NTD β-thalassemia. It is a daily electronic diary with recall of symptoms during the past 24 hours, composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness (lack of energy) when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness (lack of strength) when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Shortness of Breath (SoB) domain score represents the average score of items 5 and 6 above. SoB domain score ranges from 0 (best outcome, no shortness of breath) to 10 (worst outcome, extreme shortness of breath). Weekly SoB Scores represent the average of daily scores for that week. The mean of weekly scores over a continuous 12 week period (from Week 13 to Week 24) are compared to the SoB Domain Score at baseline.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline and over a continuous 12 week period (from week 13 through week 24)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Secondary

Mean Change From Baseline in Hemoglobin Values in the Absence of Transfusion (Week 37 to Week 48)

Mean change from baseline in mean of hemoglobin (Hb) values over a continuous 12-week interval from Week 37 to Week 48 in the absence of transfusions. Baseline was defined as the average of 2 or more Hb measurements at least 1 week apart within 4 weeks before Dose 1 Day 1.

All treated participants with available measurements at Baseline and From Week 37 to Week 48. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Least Squares Mean

Standard Error

g/dL

Baseline and over a continuous 12 week period (from week 37 through week 48)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Mean Change From Baseline in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 37 to Week 48)

The FACIT-F is a multidimensional, self-report quality of life instrument which includes the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire (27 items over 4 different domains), and the Fatigue subscale (FS) component (13 items). FACIT-F version 4 has been used for this study. For the Fatigue subscale, each of the 13 items is scored from 0 ("not at all") to 4 ("very much"). The scores from individual items are summed to generated the final FS score, which ranges from 0 (best outcome) to 52 (worst outcome). The questionnaire is completed every other dose, and the mean of FS scores from Week 37 to Week 48 is compared to the FS score at baseline (last score available before start of study treatment). Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline and over a continuous 12 week period (from week 37 through week 48)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Secondary

Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score (Week 37 to Week 48)

NTDT-PRO V2.1 assess the severity of anemia-related symptoms. It's a daily recall of symptoms during the past 24 hours, composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Tiredness/Weakness (T/W) domain score represents the average score of items 1 through 4 above. T/W domain score ranges from 0 (best outcome, no tiredness/weakness) to 10 (worst outcome, extreme tiredness/weakness). Weekly T/W Scores represent the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 37 to Week 48) are compared to the T/W Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37.

All treated participants with available measurements at Baseline and at Week 37 to Week 48. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline and over a continuous 12 week period (from week 37 through week 48)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Secondary

Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Shortness of Breath (SoB) Domain Score (Week 37 to Week 48)

NTDT-PRO V2.1 assess the severity of anemia-related symptoms. It is a daily recall of symptoms during the past 24 hours, composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Shortness of Breath (SoB) domain score represents the average score of items 5 and 6 above. SoB domain score ranges from 0 (best outcome, no shortness of breath) to 10 (worst outcome, extreme shortness of breath). Weekly SoB Scores represent the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 37 to Week 48) are compared to the SoB Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline and over a continuous 12 week period (from week 37 through week 48)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Secondary

Percentage of Participants With an Increase From Baseline ≥ 3 in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 13 to Week 24)

The FACIT-Fatigue, is a multidimensional, self-report quality of life instrument. It consists of 27 core items, the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, which assesses patient function in 4 domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by a 13-item measure designed to capture cancer-related fatigue, the Fatigue subscale (FS). The items are measured on a response scale with five options (0 = not at all to 4 = very much). Participants completed the questionnaire at screening and every other dose. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13. Score is calculated by multiplying the sum of item scores by the n of items in the scale, then divided by n of items answered.

Posted

Number

95% Confidence Interval

Percent of Participants

Baseline and over a continuous 12 week period (from week 13 through week 24)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Secondary

Percentage of Participants With an Increase From Baseline ≥ 3 in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 37 to Week 48)

The FACIT-Fatigue, is a multidimensional, self-report quality of life instrument. It consists of 27 core items, the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, which assesses patient function in 4 domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by a 13-item measure designed to capture cancer-related fatigue, the Fatigue subscale (FS). The items are measured on a response scale with five options (0 = not at all to 4 = very much). Participants completed the questionnaire at screening and every other dose. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37. Score is calculated by multiplying the sum of item scores by the n of items in the scale, then divided by n of items answered.

Posted

Number

95% Confidence Interval

Percent of Participants

Baseline and over a continuous 12 week period (from week 37 through week 48)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Secondary

Mean Change From Baseline in the Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of the Medical Outcomes Study 36-Item Short Form (SF-36)

The SF-36v2 is a 36-item generic PRO questionnaire used to assess patient-reported outcomes. The SF-36 yields scores for 8 domains of health: Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role Emotional (RE), and Mental Health (MH) as well as physical component summary (PCS) and mental component summary (MCS) scores. Scores from each of the 8 domains of health are first normalized based on US general population means, then aggregated and transformed so that the scores from each of the 8 domains of health will contribute differently to the determination of PCS and MCS summary scores. PCS and MCS scores range from 0 to 100, with higher scores indicating a better quality of life. Baseline is defined as the last value taken on or before the first dose of study drug administered.

All treated participants with available measurements at Baseline, at Week 24 and at Week 48. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Least Squares Mean

Standard Error

Score on a scale

From baseline to Week 24 and from baseline to Week 48 of study treatment

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Secondary

Percentage of Participants With Improvement of Iron Overload

Iron overload was measured by Liver Iron Concentration (LIC) and Iron Chelation Therapy (ICT) daily dose. Improvement is defined as: - For participants with baseline LIC ≥3 mg/g: ≥20% reduction in LIC or ≥ 33% decrease in ICT daily dose - For participants with baseline LIC <3 mg/g: no increase in LIC >1 mg/g and not starting treatment with ICT, or no increase in ICT daily dose ≥ 33% (if on ICT at baseline)

All treated participants. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Number

Percent of participants

Week 24 and Week 48 of study treatment

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Mean Change From Baseline in Serum Ferritin

Baseline mean serum ferritin is calculated during the 24 weeks on or prior to dose 1 day 1. Post-baseline mean serum ferritin is calculated as mean of ferritin values during the last 24 weeks on or prior to the end date of the first 24 week or 48 week treatment

All treated participants with available measurements at Baseline and at week 24 or week 48. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Least Squares Mean

Standard Error

ug/L

Week 24 and Week 48 of study treatment

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Mean Change From Baseline in Liver Iron Concentration (LIC)

LIC was measured by Magnetic Resonance Imaging (MRI). Baseline is defined as the last value on or before the first dose of study drug is administered; Postbaseline is defined as the closest visit at Week 24 or Week 48. Participants with LIC value >43 are not included in the analysis.

Posted

Least Squares Mean

Standard Error

mg/g dry weight

Week 24 and Week 48 of study treatment

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Percentage of Participants Who Are Transfusion-Free Over 24 Weeks

Transfusion free is defined as the absence of any transfusion during Week 1-24 of study treatment. Participants who discontinued treatment prior to Week 24 were not considered as transfusion free during Week 1-24.

All treated participants. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Number

Percent of Participants

From first dose to Week 24

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Percentage of Participants Who Are Transfusion-Free Over 48 Weeks

Transfusion free is defined as the absence of any transfusion during Week 1-48 of study treatment. Participants who discontinued treatment prior to Week 48 were not considered as transfusion free during Week 1-48.

All treated participants. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Number

Percent of Participants

From first dose to Week 48

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Duration of the Mean Hemoglobin Increase From Baseline ≥1.0 g/dL

This outcome measure is the cumulative mean of the duration of hemoglobin response for the ≥ 1.0 g/dL during any 12-week rolling period. Any hemoglobin values within 21 days after a transfusion were excluded from the analysis.

All participants with a mean hemoglobin increase ≥1.0 g/dL. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Mean

Standard Deviation

Days

From baseline up to approximately 56 months

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Mean Change From Baseline in the 6-Minute Walk Test (6MWT) Distance

The 6MWT is typically used to objectively assess functional exercise capacity and response to medical interventions in patients with various moderate to severe diseases. Particiapnts are asked to walk as quickly as possible without running along a 30-meter corridor for six minutes, and the total distance covered during that time is measured. Baseline is defined as the last value on or before the first dose of study drug is administered. Postbaseline is defined as the closest visit at Week 24 or Week 48.

All treated participants with available measurements at Baseline and at Week 24 or Week 48. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Least Squares Mean

Standard Error

Meters

From baseline to Week 24 and from baseline to Week 48 of study treatment

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Percentage of Participants With an Increase From Baseline ≥1.5 g/dL in Mean Hemoglobin Values in the Absence of Transfusion

Percentage of participants who have an increase from baseline ≥1.5 g/dL in mean of hemoglobin (Hb) values over a continuous 12-week interval from Week 13 to Week 24 in the absence of transfusions. Baseline was defined as the average of 2 or more Hb measurements at least 1 week apart within 4 weeks before Dose 1 Day 1.

All treated participants. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Number

95% Confidence Interval

Percentage of Participants

From Week 13 to Week 24 of study treatment

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Percentage of Participants With a Decrease From Baseline ≥ RD (= 1) in the Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score

The responder definition (RD) threshold is the individual participant score change over a predetermined time period that will be interpreted as a treatment benefit. The RD for the NTDT-PRO T/W domain score was defined as ≥ 1-point decrease (ie, RD = -1) from baseline over the time from Week 13 to Week 24 or from Week 37 to Week 48. Participants with missing NTDT-PRO T/W scores at the indicated 12-week period are classified as non-responders in the analysis.

All treated participants with available measurements at Baseline and at the indicated 12-week periods. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Number

95% Confidence Interval

Percent of participants

From Week 13 to Week 24 and from Week 37 to Week 48 of study treatment

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Number of Participants Experiencing Adverse Events

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

All treated participants. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo participants who crossed over to luspatercept.

Posted

Count of Participants

Participants

From first dose to 63 days after last dose (up to approximately 56 months)

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Number of Participants With Anti-drug Antibody (ADA) Positive Test for Luspatercept

Presence of anti-drug (ACE-536/Luspatercept) antibodies was assessed every 24 weeks from serum samples. A participant is counted as 'positive' if there is any positive result captured during the study.

All treated participants. Placebo participants are assessed up to crossing over to luspatercept. The luspatercept group does not include placebo who crossed over to luspatercept.

Posted

Count of Participants

Participants

From first dose and up to 2 years following last dose, up to approximately 56 months

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
OG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.

Secondary

Apparent Clearance (CL/F) of Luspatercept

All treated participants who received the study drug.

Posted

Geometric Mean

Geometric Coefficient of Variation

L/day

Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Units	Counts
Participants	OG000

Secondary

Apparent Volume of Distribution of the Central Compartment (V1/F) of Luspatercept

All treated participants who received the study drug.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Units	Counts
Participants	OG000

Secondary

Time to Reach Maximum Concentration (Tmax) of Luspatercept

All treated participants who received the study drug.

Posted

Median

Full Range

Days

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Units	Counts
Participants	OG000

Secondary

Maximum Concentration (Cmax) of Luspatercept

All treated participants who received the study drug.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/mL

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Units	Counts
Participants	OG000

Secondary

Maximum Concentration From Steady State (Cmax,ss) of Luspatercept

All treated participants who received the study drug.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/mL

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Units	Counts
Participants	OG000

Secondary

Area Under the Curve From Steady State (AUCss) of Luspatercept

All treated participants who received the study drug.

Posted

Geometric Mean

Geometric Coefficient of Variation

day*μg/mL

ID	Title	Description
OG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	25.1	Systematic Assessment	EG0002 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Extramedullary haemopoiesis	Blood and lymphatic system disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Splenomegaly	Blood and lymphatic system disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Cardiac failure acute	Cardiac disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Myocardial infarction	Cardiac disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Myocardial ischaemia	Cardiac disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Ventricular hypokinesia	Cardiac disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Abdominal pain	Gastrointestinal disorders	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Oedema peripheral	General disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Bile duct stone	Hepatobiliary disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Biliary colic	Hepatobiliary disorders	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Cholangitis	Hepatobiliary disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Cholecystitis acute	Hepatobiliary disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Cholelithiasis	Hepatobiliary disorders	25.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected49 at risk EG0021 affected38 at risk
Abscess limb	Infections and infestations	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
COVID-19	Infections and infestations	25.1	Systematic Assessment	EG0002 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
COVID-19 pneumonia	Infections and infestations	25.1	Systematic Assessment	EG0002 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Dengue haemorrhagic fever	Infections and infestations	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Gastroenteritis	Infections and infestations	25.1	Systematic Assessment	EG0000 affected96 at risk EG0012 affected49 at risk EG0020 affected38 at risk
Influenza	Infections and infestations	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Pharyngitis	Infections and infestations	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Pilonidal disease	Infections and infestations	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Pyelonephritis acute	Infections and infestations	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Septic shock	Infections and infestations	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Tonsillitis	Infections and infestations	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Viral upper respiratory tract infection	Infections and infestations	25.1	Systematic Assessment	EG0000 affected96 at risk EG0012 affected49 at risk EG0020 affected38 at risk
Hip fracture	Injury, poisoning and procedural complications	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Pulmonary contusion	Injury, poisoning and procedural complications	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Rib fracture	Injury, poisoning and procedural complications	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Traumatic fracture	Injury, poisoning and procedural complications	25.1	Systematic Assessment	EG0005 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Haemoglobin decreased	Investigations	25.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected49 at risk EG0021 affected38 at risk
Diabetes mellitus	Metabolism and nutrition disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Hypovolaemia	Metabolism and nutrition disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Steroid diabetes	Metabolism and nutrition disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Diffuse large B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Spinal cord compression	Nervous system disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Transient ischaemic attack	Nervous system disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	25.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected49 at risk EG0021 affected38 at risk
Pregnancy	Pregnancy, puerperium and perinatal conditions	25.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected49 at risk EG0021 affected38 at risk
Proteinuria	Renal and urinary disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Renal colic	Renal and urinary disorders	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Ovarian cyst ruptured	Reproductive system and breast disorders	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Prostatic obstruction	Reproductive system and breast disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0000 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Haemothorax	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0002 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Extramedullary haemopoiesis	Blood and lymphatic system disorders	25.1	Systematic Assessment	EG0009 affected96 at risk EG0012 affected49 at risk EG0022 affected38 at risk
Palpitations	Cardiac disorders	25.1	Systematic Assessment	EG0009 affected96 at risk EG0016 affected49 at risk EG0024 affected38 at risk
Tachycardia	Cardiac disorders	25.1	Systematic Assessment	EG0006 affected96 at risk EG0012 affected49 at risk EG0022 affected38 at risk
Ear pain	Ear and labyrinth disorders	25.1	Systematic Assessment	EG0003 affected96 at risk EG0014 affected49 at risk EG0020 affected38 at risk
Vertigo	Ear and labyrinth disorders	25.1	Systematic Assessment	EG0003 affected96 at risk EG0013 affected49 at risk EG0020 affected38 at risk
Abdominal pain	Gastrointestinal disorders	25.1	Systematic Assessment	EG00018 affected96 at risk EG0015 affected49 at risk EG0024 affected38 at risk
Abdominal pain upper	Gastrointestinal disorders	25.1	Systematic Assessment	EG00015 affected96 at risk EG0013 affected49 at risk EG0025 affected38 at risk
Dental caries	Gastrointestinal disorders	25.1	Systematic Assessment	EG0005 affected96 at risk EG0012 affected49 at risk EG0020 affected38 at risk
Diarrhoea	Gastrointestinal disorders	25.1	Systematic Assessment	EG00025 affected96 at risk EG0016 affected49 at risk EG0025 affected38 at risk
Dyspepsia	Gastrointestinal disorders	25.1	Systematic Assessment	EG00018 affected96 at risk EG0012 affected49 at risk EG0023 affected38 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	25.1	Systematic Assessment	EG0005 affected96 at risk EG0013 affected49 at risk EG0020 affected38 at risk
Nausea	Gastrointestinal disorders	25.1	Systematic Assessment	EG00014 affected96 at risk EG0016 affected49 at risk EG0021 affected38 at risk
Toothache	Gastrointestinal disorders	25.1	Systematic Assessment	EG00015 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Vomiting	Gastrointestinal disorders	25.1	Systematic Assessment	EG00011 affected96 at risk EG0011 affected49 at risk EG0021 affected38 at risk
Asthenia	General disorders	25.1	Systematic Assessment	EG00019 affected96 at risk EG0015 affected49 at risk EG0020 affected38 at risk
Fatigue	General disorders	25.1	Systematic Assessment	EG00023 affected96 at risk EG00110 affected49 at risk EG0028 affected38 at risk
Influenza like illness	General disorders	25.1	Systematic Assessment	EG00025 affected96 at risk EG0013 affected49 at risk EG0022 affected38 at risk
Injection site erythema	General disorders	25.1	Systematic Assessment	EG0005 affected96 at risk EG0010 affected49 at risk EG0023 affected38 at risk
Malaise	General disorders	25.1	Systematic Assessment	EG0006 affected96 at risk EG0011 affected49 at risk EG0021 affected38 at risk
Oedema peripheral	General disorders	25.1	Systematic Assessment	EG0006 affected96 at risk EG0012 affected49 at risk EG0021 affected38 at risk
Pain	General disorders	25.1	Systematic Assessment	EG0004 affected96 at risk EG0010 affected49 at risk EG0022 affected38 at risk
Pyrexia	General disorders	25.1	Systematic Assessment	EG00030 affected96 at risk EG0019 affected49 at risk EG00211 affected38 at risk
Biliary colic	Hepatobiliary disorders	25.1	Systematic Assessment	EG0005 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Immunisation reaction	Immune system disorders	25.1	Systematic Assessment	EG00018 affected96 at risk EG0010 affected49 at risk EG0025 affected38 at risk
Bronchitis	Infections and infestations	25.1	Systematic Assessment	EG0006 affected96 at risk EG0011 affected49 at risk EG0021 affected38 at risk
COVID-19	Infections and infestations	25.1	Systematic Assessment	EG00034 affected96 at risk EG0010 affected49 at risk EG00215 affected38 at risk
Gastroenteritis	Infections and infestations	25.1	Systematic Assessment	EG00012 affected96 at risk EG0012 affected49 at risk EG0022 affected38 at risk
Helicobacter infection	Infections and infestations	25.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected49 at risk EG0022 affected38 at risk
Influenza	Infections and infestations	25.1	Systematic Assessment	EG00015 affected96 at risk EG0015 affected49 at risk EG0021 affected38 at risk
Nasopharyngitis	Infections and infestations	25.1	Systematic Assessment	EG0007 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Pharyngitis	Infections and infestations	25.1	Systematic Assessment	EG00021 affected96 at risk EG0016 affected49 at risk EG0021 affected38 at risk
Rhinitis	Infections and infestations	25.1	Systematic Assessment	EG0009 affected96 at risk EG0016 affected49 at risk EG0020 affected38 at risk
Sinusitis	Infections and infestations	25.1	Systematic Assessment	EG0004 affected96 at risk EG0011 affected49 at risk EG0022 affected38 at risk
Tonsillitis	Infections and infestations	25.1	Systematic Assessment	EG0004 affected96 at risk EG0016 affected49 at risk EG0021 affected38 at risk
Tooth abscess	Infections and infestations	25.1	Systematic Assessment	EG0006 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Upper respiratory tract infection	Infections and infestations	25.1	Systematic Assessment	EG00023 affected96 at risk EG00111 affected49 at risk EG0021 affected38 at risk
Fall	Injury, poisoning and procedural complications	25.1	Systematic Assessment	EG0002 affected96 at risk EG0010 affected49 at risk EG0023 affected38 at risk
Ligament sprain	Injury, poisoning and procedural complications	25.1	Systematic Assessment	EG0005 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Muscle strain	Injury, poisoning and procedural complications	25.1	Systematic Assessment	EG0005 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Traumatic fracture	Injury, poisoning and procedural complications	25.1	Systematic Assessment	EG0006 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Alanine aminotransferase increased	Investigations	25.1	Systematic Assessment	EG0006 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Folate deficiency	Metabolism and nutrition disorders	25.1	Systematic Assessment	EG0005 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Hyperuricaemia	Metabolism and nutrition disorders	25.1	Systematic Assessment	EG0008 affected96 at risk EG0012 affected49 at risk EG0021 affected38 at risk
Iron overload	Metabolism and nutrition disorders	25.1	Systematic Assessment	EG00014 affected96 at risk EG0015 affected49 at risk EG0020 affected38 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	25.1	Systematic Assessment	EG0009 affected96 at risk EG0014 affected49 at risk EG0022 affected38 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG00037 affected96 at risk EG0018 affected49 at risk EG00211 affected38 at risk
Back pain	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG00038 affected96 at risk EG0016 affected49 at risk EG00214 affected38 at risk
Bone pain	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG00042 affected96 at risk EG0013 affected49 at risk EG0028 affected38 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG0003 affected96 at risk EG0011 affected49 at risk EG0022 affected38 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG0003 affected96 at risk EG0013 affected49 at risk EG0021 affected38 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG0006 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG0006 affected96 at risk EG0011 affected49 at risk EG0021 affected38 at risk
Myalgia	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG00016 affected96 at risk EG0015 affected49 at risk EG0023 affected38 at risk
Neck pain	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG00012 affected96 at risk EG0012 affected49 at risk EG0021 affected38 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG0006 affected96 at risk EG0010 affected49 at risk EG0021 affected38 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG00029 affected96 at risk EG0015 affected49 at risk EG0026 affected38 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0010 affected49 at risk EG0023 affected38 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG0006 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	25.1	Systematic Assessment	EG0005 affected96 at risk EG0011 affected49 at risk EG0021 affected38 at risk
Dizziness	Nervous system disorders	25.1	Systematic Assessment	EG00019 affected96 at risk EG0014 affected49 at risk EG0023 affected38 at risk
Headache	Nervous system disorders	25.1	Systematic Assessment	EG00044 affected96 at risk EG00110 affected49 at risk EG00210 affected38 at risk
Migraine	Nervous system disorders	25.1	Systematic Assessment	EG0009 affected96 at risk EG0010 affected49 at risk EG0020 affected38 at risk
Sciatica	Nervous system disorders	25.1	Systematic Assessment	EG0005 affected96 at risk EG0010 affected49 at risk EG0021 affected38 at risk
Anxiety	Psychiatric disorders	25.1	Systematic Assessment	EG00010 affected96 at risk EG0010 affected49 at risk EG0021 affected38 at risk
Insomnia	Psychiatric disorders	25.1	Systematic Assessment	EG00014 affected96 at risk EG0011 affected49 at risk EG0021 affected38 at risk
Albuminuria	Renal and urinary disorders	25.1	Systematic Assessment	EG0002 affected96 at risk EG0010 affected49 at risk EG0022 affected38 at risk
Dysuria	Renal and urinary disorders	25.1	Systematic Assessment	EG0006 affected96 at risk EG0011 affected49 at risk EG0020 affected38 at risk
Renal cyst	Renal and urinary disorders	25.1	Systematic Assessment	EG0001 affected96 at risk EG0013 affected49 at risk EG0020 affected38 at risk
Dysmenorrhoea	Reproductive system and breast disorders	25.1	Systematic Assessment	EG0008 affected96 at risk EG0011 affected49 at risk EG0021 affected38 at risk
Menstruation irregular	Reproductive system and breast disorders	25.1	Systematic Assessment	EG00013 affected96 at risk EG0013 affected49 at risk EG0022 affected38 at risk
Ovarian cyst	Reproductive system and breast disorders	25.1	Systematic Assessment	EG0003 affected96 at risk EG0011 affected49 at risk EG0023 affected38 at risk
Cough	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG00024 affected96 at risk EG0011 affected49 at risk EG0022 affected38 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0005 affected96 at risk EG0010 affected49 at risk EG0021 affected38 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG00012 affected96 at risk EG0011 affected49 at risk EG0021 affected38 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0008 affected96 at risk EG0012 affected49 at risk EG0021 affected38 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG00023 affected96 at risk EG0016 affected49 at risk EG0021 affected38 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected49 at risk EG0022 affected38 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0000 affected96 at risk EG0012 affected49 at risk EG0022 affected38 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0007 affected96 at risk EG0013 affected49 at risk EG0020 affected38 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	25.1	Systematic Assessment	EG0004 affected96 at risk EG0013 affected49 at risk EG0021 affected38 at risk
Erythema	Skin and subcutaneous tissue disorders	25.1	Systematic Assessment	EG0007 affected96 at risk EG0010 affected49 at risk EG0021 affected38 at risk
Pruritus	Skin and subcutaneous tissue disorders	25.1	Systematic Assessment	EG0003 affected96 at risk EG0010 affected49 at risk EG0022 affected38 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	25.1	Systematic Assessment	EG0007 affected96 at risk EG0011 affected49 at risk EG0021 affected38 at risk
Hypertension	Vascular disorders	25.1	Systematic Assessment	EG00021 affected96 at risk EG0011 affected49 at risk EG0027 affected38 at risk
Prehypertension	Vascular disorders	25.1	Systematic Assessment	EG00023 affected96 at risk EG0017 affected49 at risk EG0023 affected38 at risk

ID	Term
D013789	Thalassemia
D017086	beta-Thalassemia

ID	Term
D000745	Anemia, Hemolytic, Congenital
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006453	Hemoglobinopathies
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Term
D000077324	Crystalloid Solutions
D007552	Isotonic Solutions
D012996	Solutions
D004364	Pharmaceutical Preparations

ID	Title	Description
BG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.
BG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Luspatercept	Luspatercept was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle). The starting dose level was 1.00 mg/kg and could be escalated to 1.25 mg/kg and/or reduced to 0.80, 0.60, and 0.45 mg/kg. Participants were treated for a minimum of 48 weeks.	1	96	23	96	96	96
EG001	Placebo	Placebo (0.9% sodium chloride for injection) was administered as subcutaneous injection once every 3 weeks (administered on Study Day 1 of each 21-day treatment cycle) for a minimum of 48 weeks. Eligible participants entered an open-label phase and started Luspatercept treatment for up to approximately 24 months.	0	49	13	49	48	49
EG002	Open-Label Placebo-Luspatercept	Open-label phase in which participants switched from placebo and started Luspatercept treatment for up to approximately 24 months.	0	38	3	38	38	38