NCT05664737进行中（未招募）2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 189
- 试验地点
- 33
- 主要终点
- Number of participants with adverse events (AEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participant≥ 18 years with documented diagnosis of A-Thal HbH disease with Transfusion dependence defined as:.
- •i) TD participant: ≥ 6 RBC units during the 24 weeks prior to randomization. ii) NTD participant:< 6 RBC units during the 24 weeks prior to randomization(transfusion due to conditions other than A-Thal will not be considered)and, RBC transfusion-free during at least 8 weeks prior to randomization(unless transfusion was required to treat an acute medical condition other than A-Thal) 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.
- •Adult participant has Eastern Cooperative Oncology Group (ECOG) 34 score of 0 or
- •Adolescent participant 12 years to < 18 years with documented diagnosis of A-Thal HbH disease with transfusion dependence defined as:.
- •i) TD participant: ≥ 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.
- •ii) NTD participant:< 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.
- •iii) Participant has Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening.
排除标准
- •Medical Conditions: Diagnosis of A-ThalTrait, Hb Bart hydrops, ATRx A-Thal, hemoglobin S/β-thalassemia, myelodysplasia subtype anemia, or with HbE homozygous beta gene mutation. Anemia related to nutritional deficiency, anemia of chronic disease, autoimmune hemolytic anemia, or any other hemolytic anemias. Undergone episodes of hemolysis not related to A-Thal within the 8 weeks prior to randomization. Applicable for the EU only: Bleeding disorders manifested by frequent bleeding episodes (eg, menorrhagia, epistaxis, clotting disorders).
- •Participant has deep vein thrombosis (DVT), stroke or other thromboembolic event(s) (except clogged indwelling catheter) requiring medical intervention ≤ 24weeks prior to randomization.
- •Participant has uncontrolled hypertension. Controlled hypertension for this protocol is considered: blood pressure value corresponding to ≤Grade 1 according to NCI CTCAE Version 5.
- •with or without pharmacological treatment.
- •Reproductive Status: Women who are pregnant, plan to get pregnant during the study, or who are breastfeeding.
- •Prior/Concomitant: Undergone HSCTs or gene therapy (candidates for HSCT or gene therapy with waiting period of ≥ 12 months are eligible).
- •Use of hydroxyurea treatment ≤ 12 weeks prior to enrollment for NTD participants and ≤ 24 weeks for TD participants.
- •Participant who has extramedullary hematopoiesis (EMH) complications requiring treatment to control the growth of EMH mass(es) during the screening period.
- •Any medical or psychiatric condition (including active infections, recent surgery, sequelae of diseases or interventions, clinically significant laboratory abnormalities or concurrent treatment) that in the opinion of the investigator would put the participant at unacceptable risk of participating in the study or that could affect interpretability of data.
- •Other protocol-defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Transfusion Dependent (TD): Luspatercept + Best supportive care (BSC)
Experimental
干预措施: Luspatercept (Biological)
Non-transfusion Dependent (NTD): Luspatercept + BSC
Experimental
干预措施: Luspatercept (Biological)
Adult TD Cohort: Placebo + BSC
Placebo Comparator
干预措施: Placebo (Drug)
Adult NTD Cohort: Placebo + BSC
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with adverse events (AEs)
时间窗: Up to 5 years
Adolescent TD and NTD Cohorts
Pharmacokinetics (PK): Serum concentration of Luspatercept
时间窗: Up to Week 108
Adolescent TD and NTD Cohorts
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
时间窗: Up to Week 48
Adult TD Cohort
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
时间窗: Up to Week 3
Adolescent TD and NTD Cohorts
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
时间窗: Up to Week 24
Adult NTD Cohort
次要结局
- Mean change in biomarkers for hemolysis(Up to Week 48)
- Number of participants with immunogenicity(Up to 2 Years)
- Percent Change from Baseline in Biomarkers for Erythropoiesis at Week 48(Baseline, Week 48)
- Percent Change from Baseline in Biomarkers and Parameters for Iron Homeostasis at Week 48(Up to 5 Years)
- Percent Change from Baseline in HB Variants including HBH(Baseline, Week 48)
- Number of participants with antidrug antibody (ADA)(Up to 2 Years)
- Mean change in biomarkers and parameters for iron homeostasis(Up to 5 Years)
- Assessment of Hematologic Parameters(Up to Week 48)
- The change from baseline in the number of health care resource utilization (HCRU)(Up to 5 Years)
- Mean change from baseline in Pediatric Quality of Life Inventory (PedsQL) domain scores(Up to 3 Years)
- Mean change from baseline EQ-5D-5L utility index(Up to 3 Years)
- Mean change from baseline visual analogue scale (VAS) scores(Up to 3 Years)
- 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(Up to Week 108)
- The longest duration with ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units(Up to Week 108)
- Number of RBC transfusion units from week 1 to week 48(Up to Week 48)
- Change from baseline in hemoglobin in the absence of transfusion at Week 24(Up to Week 24)
- 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(Up to Week 108)
- Time Duration with an increase from baseline of ≥ 1.0 g/dL in hemoglobin values in the absence of transfusion within 48 weeks(Up to Week 48)
- 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(Up to Week 24)
- ≥ 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(Up to Week 24)
- Number of participants with AEs(Up to 5 years)
- Number of participants with laboratory abnormalities(Up to 5 Years)
- 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(Up to Week 48)
- 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(Up to Week 108)
- 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(Up to Week 48)
- 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(Up to Week 48)
- 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(Up to Week 48)
- 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(Up to Week 48)
- 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(Up to Week 48)
- The longest duration of RBC transfusion-free period for participants who achieve transfusion-free period of ≥ 12 weeks(Up to Week 108)
- 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)(Up to Week 108)
- Time from first dose to first day of response (rolling 12-week and 24-week response, both for ≥ 33% and ≥ 50% reduction)(Up to Week 108)
- Change from baseline in number of transfusion events at Week 48(Up to Week 48)
- Number of participants who achieve RBC transfusion-free period of any continuous ≥ 12 weeks during treatment(Up to Week 108)
- Number of participants who achieve RBC transfusion-free period of any continuous ≥ 24 weeks during treatment(Up to Week 108)
- Time to first transfusion(Up to Week 108)
- Number of transfusions(Within 48 Weeks)
- Number of transfusion visits/units(Within 48 Weeks)
- 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(Up to Week 48)
- 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(Up to Week 48)
- Time from first to last Hb measurement with increase from baseline by ≥ 1.0 g/dL(Up to Week 108)
- Time to the first increase from baseline of ≥ 1.0 g/dL in mean Hb value(Up to Week 48)
- 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(Up to Week 48)
- 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(Up to Week 48)
- Change from baseline in non-transfusion dependent β-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(Up to Week 48)
- Change from baseline in FACT-An FS Score at Week 24 and Week 48(Up to Week 48)
- Change from baseline in Functional Assessment of Cancer Therapy Anemia Anemia Subscale (FACT-An AS) at Week 24 and Week 48(Up to Week 48)
- Number of participants with at least one hemolytic crisis(Up to Week 108)
- Rate of hemolytic crises(Up to Week 108)
- Time to first hemolytic crisis(Up to Week 108)
- Time to second hemolytic crisis(Up to Week 108)
- Change from baseline in hemolysis markers at Week 24 and Week 48(Up to Week 48)
- Change from baseline in the 6-minute walk test (6MWT) distance at Week 24 and Week 48(Up to Week 48)
- Pharmacokinetics (PK): Serum concentration of Luspatercept(Up to Week 108)
- Change in mean corpuscular volume (MCV) at Week 48(Baseline, Week 48)
- Change in mean corpuscular hemoglobin (MCH) at Week 48(Baseline, Week 48)
- Change in nucleated red blood cells (nRBC) at Week 48(Baseline, Week 48)
- Change in red blood cells (RBC) at Week 48(Baseline, Week 48)
- The longest duration with reduction from baseline in the RBC transfusion burden(Up to Week 48)
- The number of participants with ≥ 50% reduction from baseline in RBC transfusion burden during an continuous 12 weeks during Weeks 13-48(Up to Week 48)
- The number of participants with ≥ 33% reduction from baseline in RBC transfusion burden during an continuous 24 weeks(Up to Week 48)
- 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(Up to Week 24)
- 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(Up to Week 48)
- 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(Up to Week 48)
- The longest duration with an increase from baseline of ≥1.0g/dL in mean Hb values in absence of transfusions(Up to Week 48)
研究者
研究点 (33)
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