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)

• Sponsor: Edimer Pharmaceuticals
• Information provided by (Responsible Party): Edimer Pharmaceuticals

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
X-Linked Hypohidrotic Ectodermal Dysplasia	Drug: EDI200	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Study Start Date: April 2013
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

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 Name: 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 Name: APO200

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of adverse events [ Time Frame: Up to 6 months after dosing ]
2. To assess the antibody response to EDI200 [ Time Frame: Up to 6 months after dosing ]
3. Area under the concentration time curve to the end of the dosing period (AUC0-tau) of EDI200 [ Time Frame: 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 ]
4. Peak plasma concentration (Cmax) of EDI200 [ Time Frame: 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 ]
5. Time at which maximum concentration is observed (Tmax) of EDI200 [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: up to 14 Days (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California, San Francisco

San Francisco, California, United States, 94143

United States, District of Columbia

Children's National Medical Center

Washington, District of Columbia, United States, 20010

United States, Missouri

Washington University School of Medicine

St. Louis, Missouri, United States, 63110

France

Hôpital Necker-Enfants Malades

Paris, France, 75015

Germany

University Hospital Erlangen

Erlangen, Bavaria, Germany, 91054

Italy

Azienda Ospedaliera-Polo Universitario "Luigi Sacco"

Milan, Italy, 20157

United Kingdom

University Hospital of Wales

Cardiff, United Kingdom, CF14 4XW

Sponsors and Collaborators

Edimer Pharmaceuticals

Investigators

• Study Director: Kenneth Huttner, MD, PhD; Edimer Pharmaceuticals

More Information

• Responsible Party: Edimer Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01775462 History of Changes
• Other Study ID Numbers: ECP-002
• First Posted: January 25, 2013
• Last Update Posted: January 20, 2016
• Last Verified: January 2016

Keywords provided by Edimer Pharmaceuticals:

Hypohidrotic Ectodermal Dysplasia; XLHED

Additional relevant MeSH terms:

Ectodermal Dysplasia; Ectodermal Dysplasia 1, Anhidrotic; Hyperplasia; Pathologic Processes; Abnormalities, Multiple; Congenital Abnormalities; Skin Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Genetic Diseases, X-Linked; Immunoglobulin Fc Fragments; Immunologic Factors; Physiological Effects of Drugs