Clinical Trials List
Protocol NumberACE-536-B-THAL-001
NCT Number(ClinicalTrials.gov Identfier)NCT02604433
2016-05-02 - 2021-05-12
Phase III
Terminated4
ICD-9282.4
Thalassemias
A Phase 3, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in adults who require regular red blood cell transfusions due to beta (β)-thalassemia
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
Celgene Corporation
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 陳君明 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ta-Chih Liu Division of Hematology & Oncology
- Pei-Chin Lin Division of Pediatrics
- Hui-Hua Hsiao Division of Hematology & Oncology
- Shyh-Shin Chiou Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- 張修豪 Division of Pediatrics
- 彭信逢 Division of Radiology
- YUNG-LI YANG Division of Pediatrics
- 林凱信 Division of Pediatrics
- 周冠生 Division of Pediatrics
- SHIANN-TANG JOU Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
beta (β)-thalassemia
Objectives
The primary objective is:
To determine the proportion of subjects treated with luspatercept plus best supportive
care (BSC) versus placebo plus BSC who achieve an erythroid response, defined as
≥ 33% reduction from baseline in transfusion burden (units RBCs / time) with a
reduction of at least 2 units, from Week 13 to Week 24
The key secondary objectives are:
To evaluate the proportion of subjects who achieve ≥ 33% reduction from baseline in
transfusion burden from Week 37 to Week 48 versus placebo
To evaluate the proportion of subjects who achieve ≥ 50% reduction from baseline in
transfusion burden from Week 13 to Week 24 versus placebo
To evaluate the proportion of subjects who achieve ≥ 50% reduction from baseline in
transfusion burden from Week 37 to Week 48 versus placebo
To evaluate the mean change from baseline in transfusion burden from Week 13 to
Week 24
Test Drug
Luspatercept (ACE-536)
Active Ingredient
Luspatercept (ACE-536)
Dosage Form
Injection
Dosage
25 mg/vial, 75 mg/vial
Endpoints
Overview of Key Efficacy Assessments
The primary efficacy assessment will be:
Transfusion burden, calculated as units RBC per 12-week period, including the 12
weeks prior to Dose 1 Day 1, Week 13 to Week 24, and Week 37 to Week 48.
Additional data obtained for each transfusion will include date, volume in mL,
hematocrit of RBCs transfused, and pre-transfusion hemoglobin level.
Other efficacy assessments will include:
Liver iron concentration (LIC, mg/g dw) measured by magnetic resonance imaging
(MRI)
Daily dose of iron chelation therapy (ICT)
Serum ferritin
Total hip and lumbar spine bone mineral density (BMD) by dual energy x-ray
absorptiometry (DXA)
Myocardial iron by MRI
Quality of Life using TranQol, SF36
Healthcare resource utilization
Overview of Key Safety Assessments
All subjects will be assessed for safety by monitoring adverse events (AEs), clinical laboratory
tests, vital signs, electrocardiogram (ECG), cardiac Doppler or Multi Gated Acquisition Scan
(MUGA), antidrug antibody (ADA) testing, and Eastern Cooperative Oncology Group (ECOG)
performance status.
Overview of Pharmacokinetic Assessments
Population pharmacokinetics will be evaluated, and the relationship between serum drug
exposure and clinical endpoints of interest will be explored.
The primary efficacy assessment will be:
Transfusion burden, calculated as units RBC per 12-week period, including the 12
weeks prior to Dose 1 Day 1, Week 13 to Week 24, and Week 37 to Week 48.
Additional data obtained for each transfusion will include date, volume in mL,
hematocrit of RBCs transfused, and pre-transfusion hemoglobin level.
Other efficacy assessments will include:
Liver iron concentration (LIC, mg/g dw) measured by magnetic resonance imaging
(MRI)
Daily dose of iron chelation therapy (ICT)
Serum ferritin
Total hip and lumbar spine bone mineral density (BMD) by dual energy x-ray
absorptiometry (DXA)
Myocardial iron by MRI
Quality of Life using TranQol, SF36
Healthcare resource utilization
Overview of Key Safety Assessments
All subjects will be assessed for safety by monitoring adverse events (AEs), clinical laboratory
tests, vital signs, electrocardiogram (ECG), cardiac Doppler or Multi Gated Acquisition Scan
(MUGA), antidrug antibody (ADA) testing, and Eastern Cooperative Oncology Group (ECOG)
performance status.
Overview of Pharmacokinetic Assessments
Population pharmacokinetics will be evaluated, and the relationship between serum drug
exposure and clinical endpoints of interest will be explored.
Inclution Criteria
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Male or female, 18 years of age at the time of signing the informed consent document
(ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule (eg, not scheduled to receive
HSCT) and other protocol requirements.
4. Documented diagnosis of β-thalassemia or Hemoglobin E/β-thalassemia.
5. Regularly transfused, defined as: 6-20 RBC units*
in the 24 weeks prior to randomization and
no transfusion-free period for ≥ 35 days during that period.
* 1 unit in this protocol refers to a quantity of packed RBCs derived from approximately 400-500 mL of donated
blood.
6. Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
7. 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). FCBP participating in the
study must:
a. Have two 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.
b. Either commit to true abstinence** from heterosexual contact (which must be
reviewed on a monthly basis and source documented) or agree to use, and be able to
comply with, effective contraception without interruption, 28 days prior to starting
investigational product, during the study therapy (including dose interruptions), and
for 12 weeks (approximately five times the mean terminal half-life of luspatercept
based on multiple-dose PK data) after discontinuation of study therapy.
8. 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 five times the mean terminal half-life of
luspatercept based on multiple-dose PK data) following investigational product
discontinuation, even if he has undergone a successful vasectomy.
** True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception.]
Subjects must satisfy the following criteria to be enrolled in the study:
1. Male or female, 18 years of age at the time of signing the informed consent document
(ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule (eg, not scheduled to receive
HSCT) and other protocol requirements.
4. Documented diagnosis of β-thalassemia or Hemoglobin E/β-thalassemia.
5. Regularly transfused, defined as: 6-20 RBC units*
in the 24 weeks prior to randomization and
no transfusion-free period for ≥ 35 days during that period.
* 1 unit in this protocol refers to a quantity of packed RBCs derived from approximately 400-500 mL of donated
blood.
6. Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
7. 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). FCBP participating in the
study must:
a. Have two 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.
b. Either commit to true abstinence** from heterosexual contact (which must be
reviewed on a monthly basis and source documented) or agree to use, and be able to
comply with, effective contraception without interruption, 28 days prior to starting
investigational product, during the study therapy (including dose interruptions), and
for 12 weeks (approximately five times the mean terminal half-life of luspatercept
based on multiple-dose PK data) after discontinuation of study therapy.
8. 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 five times the mean terminal half-life of
luspatercept based on multiple-dose PK data) following investigational product
discontinuation, even if he has undergone a successful vasectomy.
** True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception.]
Exclusion Criteria
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Any significant medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from participating in the study.
2. Any condition including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study.
3. Any condition that confounds the ability to interpret data from the study.
4. A diagnosis of Hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg, Hemoglobin
H); β-thalassemia combined with α-thalassemia is allowed.
5. Evidence of active hepatitis C (HCV) infection, or active infectious hepatitis B, or known
positive human immunodeficiency virus (HIV).
6. DVT or stroke requiring medical intervention ≤ 24 weeks prior to randomization.
7. Chronic anticoagulant therapy ≤ 28 days prior to randomization, LMW heparin for SVT
and chronic aspirin are allowed.
8. Platelet count > 1000 x 109
/L
9. Insulin-dependent diabetes, ie, chronic treatment with insulin.
10. Treatment with another investigational drug or device ≤ 28 days prior to randomization.
11. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
12. Use of an erythropoiesis-stimulating agent (ESA) ≤ 24 weeks prior to randomization.
13. Iron chelation therapy, if initiated ≤ 24 weeks prior to randomization (allowed if initiated
> 24 weeks before or during treatment).
14. Hydroxyurea treatment ≤ 24 weeks prior to randomization.
15. Pregnant or lactating females.
16. Uncontrolled hypertension. Controlled hypertension for this protocol is considered
≤ Grade 1 according to NCI CTCAE version 4.0 (current active minor version).
17. Major organ damage, including:
a. Liver disease with alanine aminotransferase (ALT) > 3 x the upper limit of
normal (ULN) or histopathological evidence of liver cirrhosis/fibrosis on liver
biopsy;
b. 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 within 6 months of randomization.
c. Lung disease, including pulmonary fibrosis or pulmonary hypertension which are
clinically significant.
d. Creatinine clearance < 60 mL/min (per Cockroff-Gault method).
18. Proteinuria ≥ Grade 3 according to NCI CTCAE version 4.0 (current active minor
version).
19. Adrenal insufficiency.
20. Major surgery ≤ 12 weeks prior to randomization (subjects must have completely
recovered from any previous surgery prior to randomization).
21. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant
proteins or excipients in the investigational product (see Investigator Brochure).
22. Cytotoxic agents, immunosuppressants ≤ 28 days prior to randomization.
The presence of any of the following will exclude a subject from enrollment:
1. Any significant medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from participating in the study.
2. Any condition including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study.
3. Any condition that confounds the ability to interpret data from the study.
4. A diagnosis of Hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg, Hemoglobin
H); β-thalassemia combined with α-thalassemia is allowed.
5. Evidence of active hepatitis C (HCV) infection, or active infectious hepatitis B, or known
positive human immunodeficiency virus (HIV).
6. DVT or stroke requiring medical intervention ≤ 24 weeks prior to randomization.
7. Chronic anticoagulant therapy ≤ 28 days prior to randomization, LMW heparin for SVT
and chronic aspirin are allowed.
8. Platelet count > 1000 x 109
/L
9. Insulin-dependent diabetes, ie, chronic treatment with insulin.
10. Treatment with another investigational drug or device ≤ 28 days prior to randomization.
11. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
12. Use of an erythropoiesis-stimulating agent (ESA) ≤ 24 weeks prior to randomization.
13. Iron chelation therapy, if initiated ≤ 24 weeks prior to randomization (allowed if initiated
> 24 weeks before or during treatment).
14. Hydroxyurea treatment ≤ 24 weeks prior to randomization.
15. Pregnant or lactating females.
16. Uncontrolled hypertension. Controlled hypertension for this protocol is considered
≤ Grade 1 according to NCI CTCAE version 4.0 (current active minor version).
17. Major organ damage, including:
a. Liver disease with alanine aminotransferase (ALT) > 3 x the upper limit of
normal (ULN) or histopathological evidence of liver cirrhosis/fibrosis on liver
biopsy;
b. 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 within 6 months of randomization.
c. Lung disease, including pulmonary fibrosis or pulmonary hypertension which are
clinically significant.
d. Creatinine clearance < 60 mL/min (per Cockroff-Gault method).
18. Proteinuria ≥ Grade 3 according to NCI CTCAE version 4.0 (current active minor
version).
19. Adrenal insufficiency.
20. Major surgery ≤ 12 weeks prior to randomization (subjects must have completely
recovered from any previous surgery prior to randomization).
21. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant
proteins or excipients in the investigational product (see Investigator Brochure).
22. Cytotoxic agents, immunosuppressants ≤ 28 days prior to randomization.
The Estimated Number of Participants
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Taiwan
50 participants
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Global
300 participants
