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

• ClinicalTrials.gov Identifier: NCT03406962
• Recruitment Status: Completed
• First Posted: January 23, 2018
• Results First Posted: October 28, 2021
• Last Update Posted: November 3, 2021
• Sponsor: Magenta Therapeutics, Inc.
• Information provided by (Responsible Party): Magenta Therapeutics, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Inherited Metabolic Disorders (IMD)	Drug: MGTA-456	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: February 9, 2018
• Actual Primary Completion Date: February 10, 2020
• Actual Study Completion Date: January 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: MGTA-456; MGTA-456 is an expanded CD34+ cell therapy investigational product used in replacement of single umbilical cord blood transplantation.	Drug: MGTA-456; Hematopoietic stem cell transplantation will be done with the cell therapy product MGTA-456.; Other Name: HSC835

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Engraftment [ Time Frame: 42 days ]
   Engraftment is defined as achieving an absolute neutrophil count (ANC) ≥0.5 × 10⁹/L for 3 consecutive days.

Secondary Outcome Measures :

1. Number of Participants With Infusion Toxicities [ Time Frame: 48 hours ]
   Incidence of treatment-emergent adverse events (AEs) within 48 hours after MGTA-456 administration

Eligibility Criteria

• Ages Eligible for Study: 0 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Sponsors and Collaborators

Magenta Therapeutics, Inc.

Investigators

• Study Director: Magenta Study Coordinator; Magenta Therapeutics

  Study Documents (Full-Text)

Documents provided by Magenta Therapeutics, Inc.:

Study Protocol  [PDF] January 10, 2020

Statistical Analysis Plan  [PDF] February 15, 2021

More Information

• Responsible Party: Magenta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03406962
• Other Study ID Numbers: IMD-001
• First Posted: January 23, 2018
• Results First Posted: October 28, 2021
• Last Update Posted: November 3, 2021
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Magenta Therapeutics, Inc.:

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

Additional relevant MeSH terms:

Metabolic Diseases; Disease; Pathologic Processes