A Study to Determine the Efficacy and Safety of Luspatercept in Adult and Adolescent Participants With Alpha (α)-Thalassemia

Anemia Clinical Trial

Official title:

A Phase 2, Study for the Treatment of Anemia With Alpha (α)-Thalassemia to Determine the Efficacy and Safety of Luspatercept (BMS-986346/ACE-536) in Adults and Evaluate the Safety and Pharmacokinetics in Adolescents

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05664737
• Other study ID #: CA056-015
• Secondary ID: 2022-502328-35
• Status: Recruiting
• Phase: Phase 2
• Start date: December 9, 2022
• Est. completion date: June 18, 2026

Study information

• Verified date: February 2024
• Source: Bristol-Myers Squibb
• Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the efficacy and safety of luspatercept plus best supportive care (BSC) vs placebo plus BSC on anemia in adult participants with α-thalassemia hemoglobin H (HbH) disease and determine the safety and drug levels in adolescent participants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 249
• Est. completion date: June 18, 2026
• Est. primary completion date: November 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion Criteria:

• Adult participant = 18 years with documented diagnosis of a-thalassemia HbH disease with Transfusion dependence for TD participants defined as = 6 RBC units during the 24 weeks prior to randomization and no transfusion-free period for > 56 days during the 24 weeks prior to randomization.
• Adult participant = 18 years with documented diagnosis of a-thalassemia HbH disease with Transfusion dependence for NTD participants defined as < 6 RBC units during the 24 weeks prior to randomization and, RBC transfusion-free during at least 8 weeks prior to randomization and, mean baseline Hb = 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.
• Adolescent participant 12 years to < 18 years with documented diagnosis of a-thalassemia HbH disease with Transfusion dependence for TD participants defined as = 4 RBC events during the 24 weeks prior to enrollment and, no transfusion-free period for > 56 days during the 24 weeks prior to enrollment. Participants must have a history of regular transfusions for at least 2 years.
• Adolescent participant 12 years to < 18 years with documented diagnosis of a-thalassemia HbH disease with Transfusion dependence for NTD participants defined as < 4 RBC events during the 24 weeks prior to enrollment and RBC transfusion-free during at least 8 weeks prior to enrollment and, mean baseline Hb = 10 g/dL, based on a minimum of 2 measurements = 1 week apart within 4 weeks prior to enrollment, hemoglobin values within 21 days post-transfusion will be excluded.
• Adolescent participant has Karnofsky (age =16 years) or Lansky (age < 16 years) performance status score = 50 at screening.

Key Exclusion Criteria:

• Participants must not have a diagnosis of a-thalassemia Trait, Hb Bart hydrops, ATRx a-thalassemia, hemoglobin S/ß-thalassemia, myelodysplasia subtype anemia, or with HbE homozygous beta gene mutation.
• Participants must not have anemia related to nutritional deficiency, anemia of chronic disease, autoimmune hemolytic anemia, or any other hemolytic anemias.
• Participants must not have bleeding disorders manifested by frequent bleeding episodes.
• Participants must not have undergone episodes of hemolysis not related to alpha-thalassemia within the 8 weeks prior to randomization.
• Participants must not have prior exposure to gene therapy to treat a-thalassemia.
• Participants must not have undergone hematopoietic stem cell transplantation (HSCT) Note: Other protocol-defined inclusion/exclusion criteria apply.

Related Conditions & MeSH terms

• Anemia
• Thalassemia

Intervention

Biological:
• Luspatercept
Specified dose on specified days

Drug:
• Placebo
Specified dose on specified days

Locations

Country	Name	City	State
Canada	Local Institution - 0008	Halifax	Nova Scotia
China	The First People's Hospital of Foshan	Foshan	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Hainan General Hospital	Haikou
China	Local Institution - 0011	Haikou
China	First People's Hospital of Yunnan Province	Kunming	Yunnan
China	Liuzhou People's Hospital	Liuzhou
China	Maoming People's Hospital	Maoming Shi	Guangdong
China	The First Affiliated Hospital of Guangxi Medical University	Nanning
China	People's Liberation Army The 923rd Hospital	Nanning Shi	Guangxi
Greece	"General Hospital ""IPPOKRATEIO"""	Athens
Greece	Local Institution - 0009	Goudi
Greece	General Hospital of Larissa	Larissa	E
Greece	Local Institution - 0018	Rio	G
Greece	Local Institution - 0005	Thessaloniki	B
Hong Kong	Local Institution - 0025	Hong Kong	HK
Hong Kong	Local Institution - 0024	Hong Kong Island
Italy	Local Institution - 0022	Cagliari	CA
Italy	Local Institution - 0026	Genova	GE
Italy	Local Institution - 0019	Napoli
Italy	Local Institution - 0028	Napoli
Italy	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Orbassano	TO
Taiwan	Local Institution - 0010	Kaohsiung	KHH
Taiwan	Local Institution - 0004	Nan Gang Qu	TPE
Taiwan	China Medical University Hospital	Taichung	TXG
Thailand	Siriraj Hospital	Bangkok
Turkey	Local Institution - 0027	Altindag
Turkey	Local Institution - 0021	Topkapi

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

Canada,  China,  Greece,  Hong Kong,  Italy,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with = 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 12 weeks during Week 13-48 compared to 12-week interval immediately prior to date of first dose	Adult TD Cohort	Up to Week 48
Primary	Number of participants with an increase from baseline of = 1.0 grams (g)/decilitre (dL) in mean hemoglobin (Hb) values over the continuous 12-week interval from Week 13 to Week 24 in the absence of RBC transfusion	Adult NTD Cohort	Up to Week 24
Primary	Dose-limiting toxicities (DLTs) defined as observance of = Grade 3-related hemolytic crises or = Grade 3-related event outside of the known safety profile occurring within the 21 days from their first dose of study therapy	Adolescent TD and NTD Cohorts	Up to Week 3
Primary	Number of participants with adverse events (AEs)	Adolescent TD and NTD Cohorts	Up to 8.5 years
Primary	Pharmacokinetics (PK): Serum concentration of Luspatercept	Adolescent TD and NTD Cohorts	Up to Week 102
Secondary	Number of participants with = 33% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 24-week interval on treatment compared to 24-week interval immediately prior to date of first dose	Adult TD Cohort	Up to Week 108
Secondary	The longest duration with = 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units	Adult TD Cohort	Up to Week 108
Secondary	Number of RBC transfusion units from week 1 to week 48	Adult and Adolescent TD Cohorts	Up to Week 48
Secondary	Change from baseline in hemoglobin in the absence of transfusion at Week 24	Adult and Adolescent NTD Cohorts	Up to Week 24
Secondary	The longest duration of an increase from baseline of = 1.0 g/dL in mean hemoglobin values starting from Week 13 in the absence of transfusion	Adult NTD Cohort	Up to Week 108
Secondary	Time Duration with an increase from baseline of = 1.0 g/dL in hemoglobin values in the absence of transfusion within 48 weeks	Adult NTD Cohort	Up to Week 48
Secondary	Number of participants with an increase from baseline of =1.0 g/dL in mean Hb values over the continuous 12- week interval in the absence of transfusion	Adult NTD Cohort	Up to Week 24
Secondary	= 3 Increase from Baseline in Functional Assessment of Cancer Therapy Anemia Fatigue Subscale (FACT-An FS) Score from Baseline to the period from Week 13 to Week 24	Adult NTD Cohort	Up to Week 24
Secondary	Number of participants with AEs	Adult and Adolescent TD and NTD Cohorts	Up to 5 years
Secondary	Number of participants with laboratory abnormalities	Adult TD and NTD Cohorts	Up to 5 Years
Secondary	Number of participants with immunogenicity	Adult TD and NTD Cohorts	Up to 5 Years
Secondary	Number of participants with = 50% reduction from baseline in RBC transfusion burden during any continuous 24-week interval within 48 weeks compared to the 24-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Secondary	Number of participants with = 33% reduction from baseline in RBC transfusion burden during any continuous 12-week interval compared to the 12-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 108
Secondary	Number of participants with = 33% reduction from baseline in RBC transfusion burden from Week 13 to Week 24 and Week 37 to Week 48 compared to the 12-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Secondary	Number of participants with = 33% reduction from baseline in RBC transfusion burden from Week 1 to Week 24 and Week 25 to Week 48 compared to the 24-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Secondary	Number of participants with = 50% reduction from baseline in RBC transfusion burden from Week 13 to Week 24 and Week 37 to Week 48 compared to the 12-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Secondary	Number of participants with = 50% reduction from baseline in RBC transfusion burden from Week 1 to Week 24 and Week 25 to Week 48 compared to the 24-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Secondary	Change from baseline in total RBC units transfused from Week 1 to Week 24, Week 25 to Week 48, and Week 1 to Week 48	Adult TD Cohort	Up to Week 48
Secondary	The longest duration of RBC transfusion-free period for participants who achieve transfusion-free period of = 12 weeks	Adult TD Cohort	Up to Week 108
Secondary	The longest duration of reduction in transfusion burden for participants who achieve a response (rolling 12-week and 24-week response, both for = 33% and = 50% reduction)	Adult TD Cohort	Up to Week 108
Secondary	Time from first dose to first day of response (rolling 12-week and 24-week response, both for = 33% and = 50% reduction)	Adult TD Cohort	Up to Week 108
Secondary	Change from baseline in number of transfusion events at Week 48	Adult TD Cohort	Up to Week 48
Secondary	Number of participants who achieve RBC transfusion-free period of any continuous = 12 weeks during treatment	Adult and Adolescent TD and NTD Cohorts	Up to Week 108
Secondary	Number of participants who achieve RBC transfusion-free period of any continuous = 24 weeks during treatment	Adult and Adolescent TD and NTD Cohorts	Up to Week 108
Secondary	Time to first transfusion	Adult and Adolescent NTD Cohorts	Up to Week 108
Secondary	Number of transfusions	Adult NTD Cohort	Up to Week 48
Secondary	Number of transfusion visits/units	Adult NTD Cohort	Up to Week 48
Secondary	Change from baseline in mean hemoglobin values over the continuous 12-week interval from Week 13 to Week 24 and Week 37 to Week 48 in the absence of transfusions	Adult TD and NTD Cohorts	Up to Week 48
Secondary	Number of participants achieving an increase from baseline of =1.0g/dL or =1.5g/dL in mean Hb values in absence of transfusions from Week 13 to Week 24, Week 37 to Week 48 and during any continuous 12-week window within 24 weeks and 48 weeks	Adult NTD Cohort	Up to Week 48
Secondary	Time from first to last Hb measurement with increase from baseline by = 1.0 g/dL	Adult NTD Cohorts	Up to Week 108
Secondary	Time to the first increase from baseline of = 1.0 g/dL in mean Hb value	Adolescent NTD Cohort	Up to Week 48
Secondary	Number of participants who achieve an increase in mean Hb of >10g/dL values during any continuous 12-week and 24-week interval within 48 weeks in the absence of transfusions	Adult NTD Cohort	Up to Week 48
Secondary	Change from baseline in self-reported health-related quality of life (HRQoL) assessed by physical component summary (PCS) and mental component summary (MCS) of 36-item short-form health survey version2 (SF-36v2) at Week 24 and Week 48	Adult TD and NTD Cohorts	Up to Week 48
Secondary	Change from baseline in non-transfusion dependent ß-thalassemia patient-reported outcome (NTDT-PRO) Tiredness/weakness (T/W) and shortness of breath (SoB) domain scores from Week 13 to Week 24 and from Week 37 to Week 48	Adult NTD Cohort	Up to Week 48
Secondary	Change from baseline in FACT-An FS Score at Week 24 and Week 48	Adult NTD Cohort	Up to Week 48
Secondary	Change from baseline in Functional Assessment of Cancer Therapy Anemia Anemia Subscale (FACT-An AS) at Week 24 and Week 48	Adult NTD Cohort	Up to Week 48
Secondary	Number of participants with at least one hemolytic crisis	Adult TD and NTD Cohorts	Up to Week 108
Secondary	Rate of hemolytic crises	Adult TD and NTD Cohorts	Up to Week 108
Secondary	Time to first hemolytic crisis	Adult TD and NTD Cohorts	Up to Week 108
Secondary	Time to second hemolytic crisis	Adult TD and NTD Cohorts	Up to Week 108
Secondary	Change from baseline in hemolysis markers at Week 24 and Week 48	Adult TD and NTD Cohorts:	Up to Week 48
Secondary	Change from baseline in the 6-minute walk test (6MWT) distance at Week 24 and Week 48	Adult NTD Cohort	Up to Week 48
Secondary	Pharmacokinetics (PK): Serum concentration of Luspatercept	Adult and Adolescent TD and NTD Cohorts	Up to Week 108
Secondary	Percent Change from Baseline in Biomarkers for Erythropoiesis at Week 84	Adult TD and NTD Cohorts; The biomarkers for erythropoiesis to be evaluated include Hb variants including hemoglobin H (HbH), sTfR1, erythropoietin (EPO), growth differentiation factor (GDF11), GDF8, GDF15. The change will be measured as a percentage of change from baseline for all the biomarkers.	Baseline, Week 84
Secondary	Percent Change from Baseline in Biomarkers and Parameters for Iron Homeostasis at Week 84	Adult TD and NTD Cohorts; The biomarkers and parameters for iron homeostasis to be evaluated include hepcidin, erythroferrone (ERFE), serum ferritin, liver iron concentration (LIC), myocardial iron, iron chelation therapy (ICT).; The change will be measured as a percentage of change from baseline for all the biomarkers.	Baseline, Week 84
Secondary	Change in mean corpuscular volume (MCV) at Week 48	Adult TD and NTD Cohorts	Baseline, Week 48
Secondary	Change in mean corpuscular hemoglobin (MCH) at Week 48	Adult TD and NTD Cohorts	Baseline, Week 48
Secondary	Change in nucleated red blood cells (nRBC) at Week 48	Adult TD and NTD Cohorts	Baseline, Week 48
Secondary	Change in red blood cells (RBC) at Week 48	Adult TD and NTD Cohorts	Baseline, Week 48
Secondary	The longest duration with reduction from baseline in the RBC transfusion burden	Adolescent TD Cohort	Up to Week 48
Secondary	The number of participants with = 50% reduction from baseline in RBC transfusion burden during an continuous 12 weeks during Weeks 13-48	Adolescent TD Cohort	Up to Week 48
Secondary	The number of participants with = 33% reduction from baseline in RBC transfusion burden during an continuous 24 weeks	Adolescent TD Cohort	Up to Week 48
Secondary	Number of participants achieving an increase from baseline of =1.0g/dL in mean Hb values in absence of transfusions from Week 13 to Week 24	Adolescent NTD Cohort	Up to Week 24
Secondary	Cumulative time (in weeks) with an increase from baseline of =1.0g/dL in mean Hb values in absence of RBC transfusions within 48 weeks	Adolescent NTD Cohort	Up to Week 48
Secondary	Number of participants who achieve an increase in mean Hb of >10g/dL values during any continuous 12-week interval during week 13 to week 48 in the absence of transfusions	Adolescent NTD Cohort	Up to Week 48
Secondary	The longest duration with an increase from baseline of =1.0g/dL in mean Hb values in absence of transfusions	Adolescent NTD Cohort	Up to Week 48
Secondary	Number of participants with antidrug antibody (ADA)	Adolescent TD and NTD Cohorts	Up to Week 48
Secondary	Mean change in biomarkers for hemolysis	Adolescent TD and NTD Cohorts; Biomarkers for hemolysis to be evaluated include total/direct/indirect bilirubin, serum lactate dehydrogenase (sLDH), haptoglobin, reticulocytes and nucleated red blood cells, reticulocyte production index (RPI), and urinary urobilinogen	Up to Week 48
Secondary	Mean change in biomarkers and parameters for iron homeostasis	Adolescent TD and NTD Cohorts; The biomarkers and parameters for iron homeostasis to be evaluated include serum ferritin, LIC, myocardial iron concentration (MIC), ICT, myocardial T2(TD participants), and extramedullary hematopoiesis (EMH) mass(es) when present (NTD participants)	Up to 1 Year
Secondary	Hematologic assessments	Adolescent TD and NTD Cohorts; The hematologic assessments to be evaluated are red blood cell count, hemoglobin, hematocrit, reticulocyte count, nucleated red blood cell count, platelet count, mean cell volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution width, red blood cell morphology, and globin precipitates	Up to Week 48
Secondary	The change from baseline in the number of health care resource utilization (HCRU)	Adolescent TD and NTD Cohorts	Up to Week 48
Secondary	Mean change from baseline in Pediatric Quality of Life Inventory (PedsQL) domain scores	Adolescent TD and NTD Cohorts	Up to Week 48
Secondary	Mean change from baseline EQ-5D-5L utility index	Adolescent TD and NTD Cohorts	Up to Week 48
Secondary	Mean change from baseline visual analogue scale (VAS) scores	Adolescent TD and NTD Cohorts	Up to Week 48

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