A Trial of a Single ProHema-CB Product Transplant in Pediatric Patients With Inherited Metabolic Disorders (PROVIDE)

This is an interventional treatment trial for Metabolic Disorders Read More

Inclusion Criteria:

1. Patients must have a confirmed diagnosis of an inherited metabolic disorder (IMD) and be amenable to treatment by hematopoietic cell transplantation:

   • Mucopolysaccharidoses: Hurler Syndrome (MPS IH), MPS I-HS (Hurler-Scheie Syndrome), Hunter Syndrome (MPS II), Sanfilippo Syndrome (MPS III), or MPS VI (Maroteaux-Lamy syndrome) with early neurologic involvement and/or sensitization to enzyme replacement therapy (ERT); or
   • Leukodystrophies: Krabbe disease (Globoid Leukodystrophy), Metachromatic Leukodystrophy (MLD), Adrenoleukodystrophy (ALD and AMN); or
   • Other IMD with lysosomal storage disorder including glycoproteinoses (Alpha-Mannosidosis, Mucolipidosis II or I-Cell disease), sphingo- and other lipidoses (Sandhoff disease, Tay Sachs disease, Pelizaeus Merzbacher (PMD), Niemann-Pick disease, GM1 gangliosidosis, Wolman's disease.
2. Male and female subjects aged 1 to 18 years, inclusive.
3. Lack of 4 6/6 HLA matched non-carrier related UCB or 8/8 HLA A, B, C, DRß1 matched non-carrier related or 8/8 unrelated bone marrow donor; or donor not available within appropriate timeframe, as determined by the transplant physician.
4. Availability of suitable primary and secondary umbilical cord blood (UCB) units.

5. Adequate performance status, defined as:

   • Subjects ≥ 16 years: Karnofsky score ≥ 70%.
   • Subjects < 16 years: Lansky score ≥ 70%.
6. Cardiac: Left ventricular ejection fraction at rest must be > 40%, or shortening fraction > 26%.

7. Pulmonary:

   • Subjects > 10 years: DLCO (diffusion capacity) > 50% of predicted (corrected for hemoglobin)
   • FEV1, FVC > 50% of predicted; Note: If unable to perform pulmonary tests, then O2 saturation > 92% on room air.
8. Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) > 70mL/min/1.73m2.
9. Hepatic: Bilirubin ≤ 2.5 mg/dL (except in the case of Gilbert's syndrome, ongoing hemolytic anemia, or due to the primary IMD); and ALT, AST and Alkaline Phosphatase ≤ x 3 ULN (all elevations beyond the ULN must be secondary to the primary IMD and not a comorbid condition).
10. Signed IRB approved Informed Consent Form (ICF).

Exclusion Criteria:

1. Evidence of HIV infection or HIV positive serology.
2. Current uncontrolled bacterial, viral or fungal infection (progression of clinical symptoms despite therapy).
3. Requirement for continuous respiratory supportive therapy (e.g. ventilator). Patients on intermittent respiratory support should be discussed with the Sponsor.
4. Active problems related to chronic aspiration.
5. Uncontrolled seizures.
6. Any active malignancy or myelodysplastic syndrome or any history of malignancy.
7. Inability to give informed consent/assent or to comply with the requirements for care after allogeneic stem cell transplantation.
8. Female subjects that are breastfeeding or with a positive pregnancy (HCG) test at Screening.
9. Use of an investigational drug within 30 days prior to screening for the primary IMD.