E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Molydenum CoFactor Deficiency (MoCD) Type A |
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E.1.1.1 | Medical condition in easily understood language |
Molydenum CoFactor Deficiency |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10069687 |
E.1.2 | Term | Molybdenum cofactor deficiency |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 evaluate the safety and efficacy of ORGN001 in neonate, infant , and pediatric patients with MoCD Type A who are either treatment-naïve or who have received compassionate use ORGN001 |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of ORGN001 on MoCD-associated urine and blood biomarker concentrations - To evaluate the effect of ORGN001 on growth and development using age-appropriate assessments - To evaluate the effect of ORGN001 on pediatric measures of functional ability and activities of daily living - To characterize the pharmacokinetics (PK) of ORGN001 and the impact on pharmacodynamic (PD) biomarkers |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male or female neonatal patients (1 to 28 days of age [inclusive] at the time of ORGN001 administration, with day 1 of age corresponding to the day of birth) or infant (29 days to <2 years of age) or child (2 to 5 years of age [inclusive]) with MoCD Type A, previously untreated with ORGN001 or treated with ORGN001 through the EAP -In neonates, diagnosis of MoCD Type A, based on o Prenatal genetic diagnosis, or o Onset of clinical and/or laboratory signs and symptoms consistent with MoCD Type A within the first 28 days after birth - In infants or children, diagnosis of MoCD Type A, based on: o Confirmed genetic diagnosis (genetic confirmation of the diagnosis of MoCD Type A may be obtained after initiation of ORGN001 therapy in certain cases), biochemical profile, and clinical presentation consistent with MoCD Type A -Parent or legal guardian must have signed the informed consent form (ICF) prior to any study procedures being performed. |
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E.4 | Principal exclusion criteria |
-Diagnosis other than MoCD Type A (may be determined after the initiation of study drug) -Condition that is considered by the treating physician to be a contraindication to therapy, including evidence of abnormalities on brain imaging not attributable to MoCD Type A, or that might otherwise interfere with the patient’s participation in the study, pose any additional risk for the patient, or confound patient assessments -Antenatal and/or postnatal brain imaging prior to initiation of treatment with ORGN001 that indicates cortical or subcortical cystic encephalomalacia, clinically significant intracranial hemorrhage, or other abnormalities on brain imaging determined by the treating physician to be clinically significant -Modified Glasgow Coma Scale (mGCS) for Infants and Children score of less than 7 for more than 24 hours (does not apply to children less than 1 day of age). |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Through study completion. |
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E.5.2 | Secondary end point(s) |
- Changes in MoCD-related biomarkers (SSC, xanthine, uric acid in plasma and urine) - Changes in growth parameters (height, weight, body mass index [BMI], head circumference) - Feeding pattern assessments - Gross Motor Function Classification System Expanded and Revised (GMFCS-E&R) results - Assessments of the Bayley Scales of Infant Development® – Third Edition (Bayley – III®) Cognitive and Motor Scales as measured o For children aged 3 and above, for whom the Bayley-III is no longer appropriate, the Wechsler Preschool and Primary Scale of Intelligence – Fourth Edition (WPPSI-IV) will be administered. o For patients with severe developmental delay, the WPPSI may not be an appropriate assessment, and therefore, the Bayley-III may be administered instead. - functionnal ability and activities of daily living, measured by the Pediatric Evaluation of Disability Inventory (PEDI) - Gross Motor Function Measure (GMFM)-88 results |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
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 | No |
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 |
Argentina |
Israel |
Saudi Arabia |
Turkey |
United Kingdom |
United States |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 30 |