E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inborn errors of metabolism |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062018 |
E.1.2 | Term | Inborn error of metabolism |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of adjuvant therapy of ALD-101 in accelerating platelet engraftment in patients receiving a standard unrelated UCBT for treatment of inborn errors of metabolism |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of adjuvant therapy of ALD-101 assessed by infusional toxicity, adverse events and primary graft failure rates compared to historic controls To assess the efficacy of ALD-101 in accelerating and increasing overall rates of neutrophil engraftment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must have a confirmed diagnosis of inborn error of metabolism. Diagnosis to be confirmed by two appropriate tests (enzyme or mutation analysis) before study entry. Inborn errors of metabolism include the following: • Hurler Syndrome (MPS I) • Hurler-Scheie Syndrome • Hunter Syndrome (MPS II) • Sanfilippo Syndrome (MPS III) • Maroteau-Lamy Syndrome (MPS VI) • Krabbe Disease (Globoid Leukodystrophy) • Metachromatic Leukodystrophy (MLD) • Adrenoleukodystrophy ALD and AMN) • Sandhoff Disease • Tay Sachs Disease • Pelizaeus Merzbacher (PMD) • Neiman-Pick Disease • Alpha-mannosidosis 2. Patients must be <16 years of age at the time of study enrollment. 3. Patients must be ≥ 5 kg in weight. 4. Patients must have a good performance status (Lansky ≥80%). 5. Patients must have adequate function of other organ systems as measured by: • Creatinine < 2.0 mg/dl and creatinine clearance > 60 cc/min/1.73m2. Newborns must have a creatinine clearance > 25 cc/min. For babies < 3 months of age, the raw value on GFR must be > 1 cc/kg/min. • Hepatic transaminases (ALT/AST) <4 x normal, bilirubin <2.0mg/dl • Cardiac function by echocardiogram or radionuclide scan (ejection fraction or shortening fraction >80% of normal value for age) • Pulmonary function tests demonstrating FVC, CVC or FEV1 of >60% of predicted for age. If child is too young for PFTs, the option of crying vial capacity (CVC) testing is recommended. If CVC is not available at the investigational site, a room air pulse oxymetry oxygen ≥ 94% will be required to meet entry criteria. 6. Patient, and parent, or legal guardian must have given written informed consent according to FDA guidelines. 7. Patients must have a minimum life expectancy of at least 6 months. 8. Patient must be determined to be a good candidate for a standard UCBT according to the investigator and standard eligibility work-up at the site. 9. Patients must have an IQ >70 or if too young for IQ testing the potential to reach this endpoint by age 5. 10. Patient must have an available 4, 5, or 6/6 antigen matching unrelated UCB unit cryopreserved in a compartmentalized bag that will deliver a cell dose between ≥2.5 x 10e7cells/kg from one fraction (based on the precryopreservation cell content). The cord blood unit must be stored in a dual compartment bag or 2 bags to enable manufacturing ALD-101 prior to conventional transplantation. 11. Female patients of childbearing potential cannot be pregnant or lactating/breast-feeding and must be either surgically sterile, no menses for the previous 12 months, or must be practicing an effective method of birth control as determined by the investigator (e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with existing vasectomy).
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E.4 | Principal exclusion criteria |
1. Patients that are HIV, Hepatitis B and/or Hepatitis C positive. 2. Patients that are concurrently involved in any other clinical study that affects engraftment or immune reconstitution (e.g., other hematopoietic growth factors). 3. Patients with uncontrolled seizures, apnea, evidence of aspiration pneumonia, or evidence of brain stem involvement on MRI scans. 4. Patients with uncontrolled infections. 5. Patients with prior allogeneic stem cell transplant with cytoreduction preparative therapy within 12 months of enrollment. 6. Patients that have any comorbid condition which, in the view of the Principal Investigators, renders the patient at too high a risk from treatment complications and regimen related morbidity/mortality.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to platelet engraftment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |