E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Infantile Hypophosphatasia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049933 |
E.1.2 | Term | Hypophosphatasia |
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 |
1. To assess the efficacy of ENB-0040 in treating the skeletal manifestations of infantile HPP 2. To determine the safety and tolerability of ENB-0040 given intravenously (IV) in a single dose and subcutaneously (SC) in repeat doses |
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E.2.2 | Secondary objectives of the trial |
1. To assess the pharmacokinetics (PK) of ENB-0040 given IV and SC 2. To assess the bioavailability of SC ENB-0040 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Legal guardian(s) must provide informed consent prior to any study procedures 2. Documented diagnosis of severe HPP as indicated by: a. Total serum alkaline phosphatase at least 3 standard deviations (SD) below the mean for age b. Plasma pyridoxal 5’-phosphate at least 4 times the upper limit of normal c. Radiographic evidence of HPP, characterized by: * Flared and frayed metaphyses * Severe, generalized osteopenia * Widened growth plates d. One or more HPP-related findings: * History or presence of o Non-traumatic post-natal fracture o Delayed fracture healing * History of elevated serum calcium * Functional craniosynostosis with decreased head circumference growth * Nephrocalcinosis * Respiratory compromise e. Rachitic chest deformity and/or vitamin B6 dependent seizures f. Failure to thrive 3. Onset of symptoms prior to 6 months of age 4. Age ≤ 36 months 5. Otherwise medically stable (patient may be on ventilatory support) 6. Legal guardian(s) must be willing to comply with the study |
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E.4 | Principal exclusion criteria |
1. History of sensitivity to any of the constituents of the study drug 2. Current or prior clinically significant cardiovascular, endocrinologic, hematologic, hepatic, immunologic, metabolic, infectious, urologic, pulmonary, neurologic, dermatologic, renal condition and/or other major disease which, in the opinion of the investigator, precludes study participation 3. Treatment with an investigational drug within 1 month prior to the start of study drug administration 4. Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation) 5. Low serum calcium, phosphate or 25(OH) vitamin D 6. Current evidence of a treatable form of rickets 7. Prior treatment with bisphosphonate |
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E.5 End points |
E.5.1 | Primary end point(s) |
The efficacy of ENB-0040 will be determined by assessing the radiographic changes in skeletal disease. Standard images will be obtained at baseline and at 4, 12 and 24 weeks after initiation of ENB-0040 therapy.
Safety parameters, including spontaneously reported adverse events (AEs), infusion or injection associated reactions, vital signs, physical examination findings, laboratory assessments and anti-ENB-0040 antibody testing will be assessed for changes from baseline. In addition, any change in concomitant medications and therapies will be recorded. |
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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 | No |
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) | 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 | 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
| 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 | 2 |
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 | 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 | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 8 |