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

NCT01775462 | Completed Phase 2 DMC

• 1 other identifier: ECP-002
• Study Type: interventional
• Target: 6
• Locations: 5 countries
• Sites: 7

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.

Conditions

X-Linked Hypohidrotic Ectodermal Dysplasia

Keywords

Hypohidrotic Ectodermal Dysplasia; XLHED

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (8)

• 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

Study Arms (2)

EDI200, 3mg/kg

EXPERIMENTAL

Five doses of EDI200 given at 3 mg/kg twice weekly

Drug: EDI200

EDI200, 10 mg/kg

EXPERIMENTAL

Five doses of EDI200 given at 10 mg/kg twice weekly

Drug: EDI200

Interventions

EDI200 DRUG

3 or 10 mg/kg of EDI200

Also known as: APO200

EDI200, 10 mg/kg; EDI200, 3mg/kg

Eligibility Criteria

• Age: 48 Hours - 14 Days
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subjects for study drug administration must meet all of the following criteria to be enrolled:
• Male with genetic confirmation of an XLHED diagnosis.
• Subject must be at least 48 hours age and no older than 14 days.
• Subject will have reached term (defined as 37 weeks gestation or older) prior to receiving first dose study drug.
• Written informed consent of both parents (if reasonably available) must be obtained for treatment of their XLHED-affected male infant.
• 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.
• 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):
• Provide written informed consent/assent.
• 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.
• No major medical issues that the investigator considers contraindications to participation.

You may not qualify if:

• Subjects for study drug administration who meet any of the following criteria cannot be enrolled in this study:
• \. 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:
• Known hypersensitivity to pilocarpine or pilocarpine-like muscarinic agonists.
• Known hypersensitivity to lidocaine or lidocaine-like agents.
• Presence of pacemaker.
• Subjects who are not able or are not willing to comply with the procedures of this protocol.
• Subject has a condition, which in the opinion of the investigator would not allow for safe conduct of the study.

Sponsors & Collaborators

• Edimer Pharmaceuticals: lead

Study Sites (7)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

University Hospital Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Azienda Ospedaliera-Polo Universitario "Luigi Sacco"

Milan, 20157, Italy

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Related Links

• Sponsor's website

MeSH Terms

Conditions

Ectodermal Dysplasia 1, Anhidrotic

Interventions

Fc-EDA

Condition Hierarchy (Ancestors)

Ectodermal Dysplasia; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Abnormalities; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Kenneth Huttner, MD, PhD

  Edimer Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2013
• First Posted: January 25, 2013
• Study Start: April 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 20, 2016

Record last verified: 2016-01

Locations

DE (1); FR (1); US (3); IT (1); GB (1)