MGTA-456 in Patients With Inherited Metabolic Disorders Undergoing Hematopoietic Stem Cell Transplantation (HSCT)

Study Overview
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Brief Summary
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This study is designed to assess the safety and efficacy of using MGTA-456 in patients with Inherited Metabolic Disorders (IMD) undergoing stem cell transplantation.

Detailed Description
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This phase 2 study is designed to evaluate the safety and efficacy of MGTA-456 in patients with IMD after receiving myeloablative conditioning and HSCT. MGTA-456 is an expanded CD34+ cell therapy product candidate given to induce rapid and sustained hematopoietic engraftment. In patients with selected IMDs, transplant is expected to replace defective or missing protein and preserve neurodevelopment. Since MGTA-456 offers increased numbers of HSCs over standard umbilical cord blood, it is expected to reduce the risks of prolonged neutropenia and thrombocytopenia and graft failure, and potentially transplant-related mortality (TRM). Patients with Hurler syndrome (also referred to as mucopolysaccharidosis-1H (MPS-1H)), cerebral adrenoleukodystrophy (cALD), metachromatic leukodystrophy (MLD) or globoid cell leukodystrophy (GLD) (also referred to as Krabbe disease) are eligible for this study.

Official Title
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A Phase 2, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of MGTA-456 in Patients With Inherited Metabolic Disorders (IMD) Undergoing Hematopoietic Stem Cell Transplantation (HSCT)

Conditions
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Inherited Metabolic Disorders (IMD)

Intervention / Treatment
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* Drug: MGTA-456


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 2.5 years with Hurler syndrome, age 2-17 years with cerebral adrenoleukodystrophy (cALD), age < 16 years with metachromatic leukodystrophy (MLD) and age ≤ 10 years with globoid cell leukodystrophy (GLD) (also referred to as Krabbe) Cord blood grafts require genetic testing and/or demonstration of enzyme activity for patients with Hurler syndrome, MLD or GLD and are tested for very long chain fatty acids (VLCFA) to confirm there is no evidence of VLCFA consistent with ALD Adequate organ function Availability of eligible donor material Exclusion Criteria: Availability of a matched-related donor who is not a carrier of the same genetic defect Active infection at screening Prior myeloablative conditioning History of human immunodeficiency virus (HIV) infection

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 17 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: MGTA-456<br>MGTA-456 is an expanded CD34+ cell therapy investigational product used in replacement of single umbilical cord blood transplantation. | Drug: MGTA-456<br>* Hematopoietic stem cell transplantation will be done with the cell therapy product MGTA-456.<br>* Other names: HSC835;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Engraftment | Engraftment is defined as achieving an absolute neutrophil count (ANC) ≥0.5 × 10⁹/L for 3 consecutive days. | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Infusion Toxicities | Incidence of treatment-emergent adverse events (AEs) within 48 hours after MGTA-456 administration | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inherited metabolic disorders, cerebral adrenoleukodystrophy, Hurler syndrome, globoid cell leukodystrophy, Krabbe disease, metachromatic leukodystrophy, hematopoietic stem cells, hematopoietic stem cell transplant, umbilical cord blood, umbilical cord blood transplant, MGTA-456, myeloablative conditioning regimen, bone marrow transplant, mucopolysaccharidosis-1H