Phase 2 Study to Evaluate Safety, Pharmacokinetics, Immunogenicity and Pharmacodynamics/Efficacy of EDI200 in Male Infants With X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) (ECP-002)

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)

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.

Study Overview

• Status: Completed
• Conditions: X-Linked Hypohidrotic Ectodermal Dysplasia
• Intervention / Treatment: Drug: EDI200

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hopital Necker-Enfants Malades
• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • University Hospital Erlangen
• Italy
  • Milan, Italy, 20157
    • Azienda Ospedaliera-Polo Universitario "Luigi Sacco"
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days to 2 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EDI200, 3mg/kg; Five doses of EDI200 given at 3 mg/kg twice weekly	Drug: EDI200; 3 or 10 mg/kg of EDI200; Other Names: APO200
Experimental: EDI200, 10 mg/kg; Five doses of EDI200 given at 10 mg/kg twice weekly	Drug: EDI200; 3 or 10 mg/kg of EDI200; Other Names: APO200

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of adverse events	Up to 6 months after dosing
To assess the antibody response to EDI200	Up to 6 months after dosing
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
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
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 Outcome Measures

Outcome Measure	Time Frame
To assess the pharmacodynamics/efficacy (growth and development) of EDI200	Baseline and 2, 4 and 6 months
To assess the pharmacodynamics/efficacy (dentition) of EDI200	Baseline and post-six months (extension study)
To assess the pharmacodynamics/efficacy (craniofacial development) of EDI200	Baseline and 6 months
To assess the pharmacodynamics/efficacy (sweat duct density) of EDI200	Baseline and 2 and 6 months
To assess the pharmacodynamics/efficacy (sweat rate) of EDI200	Baseline and 2 and 6 months
To assess the pharmacodynamics/efficacy (Dry eye signs and symptoms) of EDI200	Baseline and 2 and 6 months
To assess the pharmacodynamics/efficacy (thermoregulation) of EDI200	Baseline and study day 21
To assess the pharmacodynamics/efficacy (molecular expression profile of skin biopsy tissue) of EDI200	Baseline, study days 1 and 15

Collaborators and Investigators

• Sponsor: Edimer Pharmaceuticals
• Investigators: Study Director: Kenneth Huttner, MD, PhD, Edimer Pharmaceuticals

Publications and helpful links

Helpful Links

• Sponsor's website

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: January 17, 2013
• First Submitted That Met QC Criteria: January 24, 2013
• First Posted (Estimate): January 25, 2013

Study Record Updates

• Last Update Posted (Estimate): January 20, 2016
• Last Update Submitted That Met QC Criteria: January 19, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: XLHED; Hypohidrotic Ectodermal Dysplasia
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Skin Diseases, Genetic; Skin Abnormalities; Abnormalities, Multiple; Hyperplasia; Ectodermal Dysplasia; Ectodermal Dysplasia 1, Anhidrotic
• Other Study ID Numbers: ECP-002