A Safety and Efficacy Study Evaluating ET-01 in Subjects With Transfusion Dependent β-Thalassaemia

Study Overview
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Brief Summary
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This is a single-arm, open label, multi-center, single-dose phase 1 study in subjects with transfusion dependent β-thalassaemia. The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using ET-01.

Official Title
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A Multicenter, Open Label Phase 1 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) in Subjects With Transfusion Dependent β-Thalassaemia

Conditions
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Transfusion Dependent Beta-Thalassaemia

Intervention / Treatment
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* Biological: ET-01


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects and/or legal representative fully understand and voluntarily sign informed consent forms. Diagnosis of transfusion dependent β-thalassemia (β-TDT) as defined by protocol. Be not appropriate to receive conventional allogeneic hematopoietic stem cell transplantation. Lansky/Karnofsky score ≥ 70%. Eligible for hematopoietic stem cell transplantation and conditioning with busulfan as per investigator's judgement. Other protocol defined inclusion criteria may apply. Key Exclusion Criteria: Subjects with associated α-thalassemia. Subjects with any clinically significant acute or uncontrolled infections. History of uncontrolled epilepsy or other mental disorders. Previous treatment with allogeneic bone marrow transplantation or gene therapy. Other protocol defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ET-01<br> | Biological: ET-01<br>* Recruited participants will receive ET-01 IV infusion following myeloablative conditioning with busulfan.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of collected AEs & SAEs |  | Within 24 months after ET-01 infusion | 
| All-cause mortality |  | From signing of informed consent up to 24 months post-ET-01 infusion | 
| Incidence of transplant-related mortality |  | From baseline (pre-transfusion) up to 12 months post-ET-01 infusion | 
| Total lymphocyte count |  | Within 24 months after ET-01 infusion | 
| Proportion of subjects with abnormal proliferation of blood cells |  | Within 24 months after ET-01 infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta-Thalassaemia, CRISPR-Cas9, Human Hematopoietic Stem and Progenitor Cells