E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034872 |
E.1.2 | Term | Phenylketonuria |
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 |
- Determine safe, effective, and tolerable dose of BMN 307
- Determine the efficacy of a single administration of BMN 307
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E.2.2 | Secondary objectives of the trial |
- Determine the efficacy of a single administration of BMN 307 on changing plasma Phe level over time
- Assess the change in dietary protein intake post-infusion following a single administration of BMN 307
- Assess changes in dietary Phe and protein intake over time following a single administration of BMN 307
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. age 15 or 18 years and older at Screening
2. Diagnosis of PKU which is a condition characterized by PAH deficiency
3. Average of two plasma Phe levels > 600 μmol/L during the Screening period
4. Ability and willingness to maintain dietary protein intake consistent with baseline intake for the duration of the study unless otherwise directed.
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E.4 | Principal exclusion criteria |
1. Subjects with primary BH4 deficiency or other forms of BH4 metabolism deficiency.
2. Clinically significant liver disease as assessed by ultrasound at Screening.
3. Prior treatment with gene therapy.
4. Detectable antibodies to the AAV5 capsid at Screening.
5. Contraindication to use of corticosteroids (CS) or history of condition that could worsen with CS therapy.
6. Hemoglobin A1C ≥ 8.0% or glucose ≥ 250 mg/dL at Screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change in mean plasma Phe levels
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change in mean plasma Phe levels
- Proportion of subjects achieving plasma Phe milestones
- Change in dietary protein intake from intact food
- Proportion of subjects consuming protein from intact food while maintaining plasma Phe
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 22 - 24, Week 24, Week 48, Week 96 |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | No |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
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 |
Australia |
Germany |
Italy |
Spain |
Taiwan |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
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 | 0 |