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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат Luspatercept
  Specified dose on specified days
• Препарат Placebo
  Specified dose on specified days

Первичные конечные точки

• 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 [Срок оценки: Up to Week 48]
• 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 [Срок оценки: Up to Week 24]
• 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 [Срок оценки: Up to Week 3]
• Number of participants with adverse events (AEs) [Срок оценки: Up to 8.5 years]
• Pharmacokinetics (PK): Serum concentration of Luspatercept [Срок оценки: Up to Week 102]

Вторичные конечные точки (12)

• 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 [Срок оценки: Up to Week 108]
• The longest duration with ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units [Срок оценки: Up to Week 108]
• Number of RBC transfusion units from week 1 to week 48 [Срок оценки: Up to Week 48]
• Change from baseline in hemoglobin in the absence of transfusion at Week 24 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Up to Week 24]
• Number of participants with AEs [Срок оценки: Up to 5 years]
• Number of participants with laboratory abnormalities [Срок оценки: Up to 5 Years]
• Number of participants with immunogenicity [Срок оценки: 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 [Срок оценки: Up to Week 48]

Критерии участия

Критерии включения

• Adult participant≥ 18 years with documented diagnosis of A-Thal HbH disease with Transfusion dependence defined as:.

• TD participant: ≥ 6 RBC units during the 24 weeks prior to randomization.
• 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 1.
• Adolescent participant 12 years to < 18 years with documented diagnosis of A-Thal HbH disease with transfusion dependence defined as:.

• 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.
• 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.
• Participant has Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening.

Критерии исключения

• 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.
• 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 5.0. 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 11 центров

• Sun Yat-sen Memorial Hospital, Sun Yat-Sen University — Гуанчжоу
• Nanfang Hospital of Southern Medical University — Гуанчжоу
• The First People's Hospital of Foshan — Foshan
• Maoming People's Hospital — Maoming Shi
• Shenzhen Second People's Hospital — Shenzhen Shi
• Liuzhou People's Hospital — Liuzhou
• People's Liberation Army The 923rd Hospital — Nanning
• Local Institution - 0011 — Haikou
• … и ещё 3 центра

Греция · 5 центров

• Local Institution - 0005 — Thessaloniki
• Local Institution - 0018 — Rio
• Local Institution - 0006 — Athens
• Local Institution - 0009 — Goudi
• Local Institution - 0007 — Larissa

Италия · 5 центров

• Local Institution - 0022 — Cagliari
• Local Institution - 0026 — Genova
• Local Institution - 0020 — Orbassano
• Local Institution - 0028 — Naples
• "Universita degli Studi della Campania ""Luigi Vanvitelli"" - AOU - Clinica Pediatrica" — Naples

Тайвань · 3 центра

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City
• National Taiwan University Hospital — Nan Gang Qu
• China Medical University Hospital — Taichung

Гонконг · 2 центра

• Local Institution - 0025 — Гонконг
• Local Institution - 0024 — Hong Kong Island

Малайзия · 2 центра

• Hospital Tunku Azizah — Kuala Lumpur
• Hospital Sultanah Aminah — Johor Bahru

Саудовская Аравия · 2 центра

• Local Institution - 0035 — Al-Ahsa
• King Saud University (KSU) - College of Medicine — Riyadh

Таиланд · 2 центра

• Siriraj Hospital — Bangkok Noi
• Naresuan University Hospital — Mueang Phitsanulok

Turkey (Türkiye) · 2 центра

• Hacettepe Üniversitesi Tıp Fakültesi — Altındağ
• Istanbul Universitesi - Istanbul Tip Fakultesi (ITF) Hastanesi — Topkapı

Канада · 1 центр

• Local Institution - 0008 — Halifax

Сингапур · 1 центр

• KK Women's and Children's Hospital — Singapore

Публикации

• Diamantidis MD, Pitsava S, Zayed O, Argyrakouli I, Karapiperis K, Chatzoulis C, Alexiou E, Manafas A, Tsangalas E, Karakoussis K. Concomitant Presence of Hb Agrinio and - -Med Deletion in a Greek Male Patient with Hemoglobinopathy H: More Severe Phenotype and Literature Review. Hematol Rep. 2023 Aug 8;15(3):483-490. doi: 10.3390/hematolrep15030050. PMID 37606495

Идентификаторы

NCT: NCT05664737 · CA056-015 · 2022-502328-35

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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