E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by inherited defects in the ectodysplasin (EDA) gene that disrupt synthesis and/or function of the primary translational product EDA-A1. The absence of normal EDA-A1 expression results in sweat and secretory gland hypoplasia predisposing XLHED-affected infants to serious and potentially life-threatening hyperthermia and pneumonia. |
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E.1.1.1 | Medical condition in easily understood language |
EDI200 is developed as a treatment of a rare genetic disorder, X-linked Hypohidrotic Ectodermal Dysplasia (XLHED) so called Christ-Siemens-Touraine Syndrome.
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072592 |
E.1.2 | Term | Hypohidrotic ectodermal dysplasia |
E.1.2 | System Organ Class | 100000004850 |
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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 safety, pharmacokinetics and immunogenicity of EDI200 administered to XLHED-affected neonates |
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E.2.2 | Secondary objectives of the trial |
• To assess the pharmacodynamics/efficacy of EDI200 administered to XLHED-affected neonates • To compare clinical data and medical history obtained from untreated male siblings to that of the XLHED-affected neonates receiving study drug
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects for study drug administration must meet all of the following criteria to be enrolled:
1. Male with genetic confirmation of an XLHED diagnosis. 2. Subject must be at least 48 hours age and no older than 14 days. 3. Subject will have reached term (defined as 37 weeks gestation or older) prior to receiving first dose study drug. 4. Written informed consent of both parents (if reasonably available) must be obtained for treatment of their XLHED-affected male infant. 5. Neither mother nor the XLHED-affected male infant known to have received an investigational study drug in the 9 months prior to study subject enrollment in this study. 6. No major medical issues that the PI considers a contraindication to participation.
Male siblings of subjects receiving study drug must meet all of the following criteria to be enrolled in the natural history sub-study (no age limit involved):
1. Provide written informed consent/assent. 2. A full or half-sibling of a study subject where the study subject has received at least one dose of study drug in the Phase 2 XLHED Neonate Study and has not yet completed the study. 3. No major medical issues that the PI considers a contraindication to participation.
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E.4 | Principal exclusion criteria |
Subjects for study drug administration who meet any of the following criteria cannot be enrolled in this study:
1. Medically significant postnatal complications or congenital anomalies outside of those considered associated with the diagnosis of XLHED.
Male siblings of subjects receiving study drug who meet any of the following criteria cannot be enrolled in the natural history sub-study:
1. Known hypersensitivity to pilocarpine or pilocarpine-like muscarinic agonists. 2. Known hypersensitivity to lidocaine or lidocaine-like agents. 3. Presence of pacemaker. 4. Subjects who are not able or are not willing to comply with the procedures of this protocol. 5. Subject has a condition, which in the opinion of the investigator would not allow for safe conduct of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Treated neonates 1. Safety laboratory measurements 2. Physical examination with weight and vital signs 3. Immunogenicity 4. Pharmacokinetics 5. Adverse events and concommitant medication |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Safety laboratory measurements: Baseline, treatment days 1, 16, 21 and 2 and 6 months after treatment
2. Physical examinations: Full physical examination: Baseline, treatment days 21, and 2, 4 and 6 months after treatment Brief physical examination: TD 0, 1, 4, 7, 11, 14 and 15
3. Immunogenicity: Baseline, treatment days 16, and 2 and 6 months after treatment
4. Pharmacokinetics: Day 0: Baseline, 15 min, 3, 8, 24, 48 hours after treatment Day 14: prior to treatment, 15 min, 3, 18, 48, 168 hours, 2 and 6 months after treatment
5. Adverse events and concommitant medication: at each visit |
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E.5.2 | Secondary end point(s) |
Treated neonates: 1. Growth and development 2. Infections and hospitalizations 3. Dental radiographs 4. Antenatal ultrasound results for tooth bud development 5. Facial photographs 6. Sweat duct number 7. Sweat rate 8. Thermoregulation 9. Dry eye evaluation 10. Skin biopsy for expression profile of molecular markers
Untreated siblings: 1. Medical history 2. Physical examination with vial signs and weight 3. Growth development 4. Infections/hospitalizations 5. Dentition 6. Facial development 7. Sweat duct number 8. Sweat rate 9. Pulmonary function 10. eNO level 11. Dry eye assessment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treated neonates 1. Growth and development Baseline and 2, 4 and 6 months after treatment
2. Infections and hospitalizations: Captured under adverse events at each study visit
3. Dental radiographs: Baseline
4. Antenatal ultrasound: Only if available as part of obsteric care
5. Facial photographs: Baseline and 6 months after treatment
6. Sweat duct number: Baseline and 2 and 6 months after treatment
7. Sweat rate: Baseline and 2 and 6 months after treatment
8. Thermoregulation: Baseline and treatment day 21
9. Dry eye evaluation: Baseline and 2 and 6 months after treatment
10. Skin biopsy: Baseline and treatment days 1, 15
Untreated siblings Medical history: study enrollment
Endpoints (1-11): Prior to study completion of affected sibling |
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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 | No |
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) | 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
| 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 | 3 |
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 |
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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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End of study: Last visit of the last subject undergoing the trial (6 month follow up) |
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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 | 2 |