Inherited Metabolic Disorders (IMD)
Conditions
Keywords
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
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.
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.
Interventions
DRUGMGTA-456
Hematopoietic stem cell transplantation will be done with the cell therapy product MGTA-456.
Sponsors
Magenta Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Engraftment | 42 days | Engraftment is defined as achieving an absolute neutrophil count (ANC) ≥0.5 × 10⁹/L for 3 consecutive days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Infusion Toxicities | 48 hours | Incidence of treatment-emergent adverse events (AEs) within 48 hours after MGTA-456 administration |
Countries
United States
Participant flow
Recruitment details
Patients were referred to clinical sites.
Pre-assignment details
Before an enrolled patient was infused with MGTA-456, the patient had to undergo a protocol-defined conditioning regimen and the proper expansion and manufacture of MGTA-456 investigational cell therapy product was confirmed.
Participants by arm
| Arm | Count |
|---|---|
| MGTA-456 MGTA-456 is an expanded CD34+ cell therapy investigational product used in replacement of single umbilical cord blood transplantation. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | MGTA-456 |
|---|---|
| Age, Continuous | 2.49 years STANDARD_DEVIATION 2.765 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 84.44 cm STANDARD_DEVIATION 23.419 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
| Weight | 13.74 kg STANDARD_DEVIATION 7.863 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 8 / 8 |
Outcome results
Primary
Number of Participants With Engraftment
Engraftment is defined as achieving an absolute neutrophil count (ANC) ≥0.5 × 10⁹/L for 3 consecutive days.
Time frame: 42 days
Population: Patients who received MGTA-456 investigational product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MGTA-456 Cohort 1 | Number of Participants With Engraftment | 6 Participants |
| MGTA-456 Cohort 2 | Number of Participants With Engraftment | 2 Participants |
Secondary
Number of Participants With Infusion Toxicities
Incidence of treatment-emergent adverse events (AEs) within 48 hours after MGTA-456 administration
Time frame: 48 hours
Population: All patients who received MGTA-456 investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MGTA-456 Cohort 1 | Number of Participants With Infusion Toxicities | Nausea | 5 Participants |
| MGTA-456 Cohort 1 | Number of Participants With Infusion Toxicities | Hypoalbuminemia | 4 Participants |
| MGTA-456 Cohort 1 | Number of Participants With Infusion Toxicities | Anemia | 4 Participants |
| MGTA-456 Cohort 1 | Number of Participants With Infusion Toxicities | Hypertension | 4 Participants |
| MGTA-456 Cohort 1 | Number of Participants With Infusion Toxicities | Hypocalcemia | 3 Participants |
| MGTA-456 Cohort 1 | Number of Participants With Infusion Toxicities | Leukopenia | 4 Participants |
| MGTA-456 Cohort 2 | Number of Participants With Infusion Toxicities | Hypocalcemia | 1 Participants |
| MGTA-456 Cohort 2 | Number of Participants With Infusion Toxicities | Nausea | 1 Participants |
| MGTA-456 Cohort 2 | Number of Participants With Infusion Toxicities | Hypertension | 1 Participants |
| MGTA-456 Cohort 2 | Number of Participants With Infusion Toxicities | Hypoalbuminemia | 1 Participants |
| MGTA-456 Cohort 2 | Number of Participants With Infusion Toxicities | Leukopenia | 0 Participants |
| MGTA-456 Cohort 2 | Number of Participants With Infusion Toxicities | Anemia | 1 Participants |