Phase 2 Study to Evaluate Safety, Pharmacokinetics, Immunogenicity and Pharmacodynamics/Efficacy of EDI200 in Male Infants With X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)

X-Linked Hypohidrotic Ectodermal Dysplasia Clinical Trial

— ECP-002  

Official title:

A Phase 2 Open-label, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity and Pharmacodynamics/Efficacy of EDI200, an EDA-A1 Replacement Protein, Administered to Male Infants With X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01775462
• Other study ID #: ECP-002
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2013
• Last updated: January 19, 2016
• Start date: April 2013
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Edimer Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 2 first-in-neonate EDI200 study will enroll treatment-naïve, XLHED-affected male newborns in the first two weeks of life. All subjects will meet entry criteria including documentation of an Ectodysplasin (EDA) mutation associated with XLHED. Following Baseline evaluations, EDI200 dosing will be initiated between day-of-life 2 and 14, with each study subject receiving 2 doses/week for a total of 5 doses. The study will enroll subjects in two cohorts with subjects in cohort 1 dosed at 3 mg/kg/dose, associated with partial efficacy, and cohort 2 dosed at 10 mg/kg/dose where enhanced efficacy was demonstrated in the most relevant preclinical model. Given the challenge of identifying families where the subject is yet to be born, it is expected that cohort size and time for recruitment will be variable.

Description:

This Phase 2 first-in-neonate EDI200 study will enroll treatment-naïve, XLHED-affected male newborns in the first two weeks of life. All subjects will meet entry criteria including documentation of an EDA mutation associated with XLHED. Following Baseline evaluations, EDI200 dosing will be initiated between day-of-life 2 and 14, with each study subject receiving 2 doses/week for a total of 5 doses. This dosing regimen mirrors that used to enhance efficacy in the dog XLHED model, considered to be most relevant to the clinical study design. The study will enroll subjects in two cohorts with subjects in cohort 1 dosed at 3 mg/kg/dose, associated with partial efficacy, and cohort 2 dosed at 10 mg/kg/dose where enhanced efficacy was demonstrated in the most relevant preclinical model. Given the challenge of identifying families where the subject is yet to be born, it is expected that cohort size and time for recruitment will be variable. The sponsor anticipates enrollment and dosing of 6-10 subjects over a 12-18 month period, 3-5 subjects per cohort.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 14 Days

Eligibility

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.

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 investigator considers contraindications to participation.

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 to be associated with the diagnosis of XLHED.

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.

Related Conditions & MeSH terms

• Ectodermal Dysplasia
• Hyperplasia
• X-Linked Hypohidrotic Ectodermal Dysplasia

Intervention

Drug:
• EDI200
3 or 10 mg/kg of EDI200

Locations

Country	Name	City	State
France	Hôpital Necker-Enfants Malades	Paris
Germany	University Hospital Erlangen	Erlangen	Bavaria
Italy	Azienda Ospedaliera-Polo Universitario "Luigi Sacco"	Milan
United Kingdom	University Hospital of Wales	Cardiff
United States	University of California, San Francisco	San Francisco	California
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Edimer Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events		Up to 6 months after dosing
Primary	To assess the antibody response to EDI200		Up to 6 months after dosing
Primary	Area under the concentration time curve to the end of the dosing period (AUC0-tau) of EDI200		Pre-dose and 15 minutes and 3, 8, 24 and 48 hours post-dose 1 and pre-dose and 15 minutes and 3, 18, 48 and 168 hours post-dose 5
Primary	Peak plasma concentration (Cmax) of EDI200		Pre-dose and 15 minutes and 3, 8, 24 and 48 hours post-dose 1 and pre-dose and 15 minutes and 3, 18, 48 and 168 hours post-dose 5
Primary	Time at which maximum concentration is observed (Tmax) of EDI200		Pre-dose and 15 minutes and 3, 8, 24 and 48 hours post-dose 1 and pre-dose and 15 minutes and 3, 18, 48 and 168 hours post-dose 5
Secondary	To assess the pharmacodynamics/efficacy (growth and development) of EDI200		Baseline and 2, 4 and 6 months
Secondary	To assess the pharmacodynamics/efficacy (dentition) of EDI200		Baseline and post-six months (extension study)
Secondary	To assess the pharmacodynamics/efficacy (craniofacial development) of EDI200		Baseline and 6 months
Secondary	To assess the pharmacodynamics/efficacy (sweat duct density) of EDI200		Baseline and 2 and 6 months
Secondary	To assess the pharmacodynamics/efficacy (sweat rate) of EDI200		Baseline and 2 and 6 months
Secondary	To assess the pharmacodynamics/efficacy (Dry eye signs and symptoms) of EDI200		Baseline and 2 and 6 months
Secondary	To assess the pharmacodynamics/efficacy (thermoregulation) of EDI200		Baseline and study day 21
Secondary	To assess the pharmacodynamics/efficacy (molecular expression profile of skin biopsy tissue) of EDI200		Baseline, study days 1 and 15