A Study Evaluating the Safety and Efficacy of the GMCN-508A Drug Product in Transfusion-dependent α-Thalassemia Participants

Официальное название

A Phase 1 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With Transfusion-dependent α-Thalassemia by Transplantation of Autologous CD34+ Cells Transduced Ex Vivo With a Lentiviral Vector (GMCN-508A Drug Product)

Обзор

This is a non-randomized, open label, single-site, single-dose, phase 1 study in up to 5 participants (between 5 and 35 years of age, inclusive) with Transfusion-dependent α-thalassemia. The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using GMCN-508A Drug Product \[autologous CD34+ hematopoietic stem cells transduced with GMCN-508A lentiviral vector encoding the human α-globin gene\].

Подробное описание

Subject participation for this study will be 5 years.

Вмешательства

• Генная терапия GMCN-508A Drug Product
  Transplant of autologous hematopoietic stem and progenitor cells transduced with GMCN-508A lentiviral vector.

Первичные конечные точки

• Percentage of Participants Who Achieved Transfusion Independence (TI) [Срок оценки: From time of drug product infusion up to 24 months]

Вторичные конечные точки (12)

• Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 24 [Срок оценки: Month 24]
• Duration of Transfusion Independence (TI) [Срок оценки: From time of drug product infusion up to 24 months]
• Time From GMCN-508A Drug Product Infusion to Achieving Transfusion Independence (TI) [Срок оценки: From time of drug product infusion up to 24 months]
• Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) [Срок оценки: From time of drug product infusion up to 24 months]
• Annualized Number of pRBC Transfusions [Срок оценки: From 12 to 24 months post drug product infusion]
• Annualized Volume of pRBC Transfusions [Срок оценки: From 12 to 24 months post drug product infusion]
• Proportion of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion. [Срок оценки: From 6 to 24 months]
• Change From Baseline in liver Iron Content by Magnetic Resonance Imaging (MRI) [Срок оценки: Baseline, Month 12 and 24]
• Change From Baseline in Cardiac T2* on MRI [Срок оценки: Baseline, Month 12 and 24]
• Change From Baseline in Serum Ferritin [Срок оценки: Baseline, Month 12 and 24]
• Time to Neutrophil Engraftment [Срок оценки: From time of drug product infusion up to 24 months]
• Proportion of Participants With Successful Platelet Engraftment [Срок оценки: From time of drug product infusion up to 24 months]

Критерии участия

Критерии включения

• The subject himself/herself or one legal guardian/agent of the subject is required to fully understand the study and voluntarily sign a written informed consent.
• Ages 5 to 35, no gender limitation.
• The clinical diagnosis of Transfusion-dependent α-Thalassemia.Transfusion dependence was defined as ≥6 Units of transfusions of pRBCs for the prior 24 weeks without >56 days of non-transfusion.
• Karnofsky Level of Performance (KPS) score or Lansky Level of Performance (LPS) score ≥70.
• Subjects were determined to undergo autologous hematopoietic stem cell transplantation and conditioning procedure by the principle investigator.
• Subjects were willing to comply with the protocol.
• Fertile Subjects are willing to take effective contraceptive measures during the study.

Критерии исключения

• Diagnosed with mild α-thalassemia, Hb Bart's edema, ATRx α-thalassemia, hemoglobin S/β-thalassemia, myelodysplastic subtype anemia, or with HbE homozygous β gene mutation, or with any type of β-thalassemia Thalassemia.
• Uncorreted Bleeding disorders with frequent bleeding (eg, menorrhagia, epistaxis, coagulation disorders).
• Bacterial, fungal, parasitic or viral infection as determined by the investigator to be clinically significant.
• Presence of severe iron overload.
• Any prior or current malignancy, myeloproliferative disorders or immunodeficiency disorders.
• Any major medical disease, laboratory test abnormality or mental illness that would render the participant ineligible for the study.
• Immediate family member with a known Familial Cancer Syndrome.
• Prior receipt of gene therapy, allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation.
• Participation in another clinical study with an investigational drug 3 months prior to Screening.
• Pregnancy, plan to be pregnant during study or breastfeeding in a postpartum female.
• Known hypersensitivity to any ingredients or excipients of the test drug.
• Eligible for allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation with a known and available donor.
• Any other condition that would render the participant ineligible for the study, as determined by the investigator.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The affiliated hospital of guangxi medical university — Nanning

Идентификаторы

NCT: NCT05757245 · GMCN-508A-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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