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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Edimer Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01775462
First received: January 17, 2013
Last updated: January 19, 2016
Last verified: January 2016
  Purpose
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 Intervention Phase
X-Linked Hypohidrotic Ectodermal Dysplasia
Drug: EDI200
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Edimer Pharmaceuticals:

Primary Outcome Measures:
  • Incidence and severity of adverse events [ Time Frame: Up to 6 months after dosing ] [ Designated as safety issue: Yes ]
  • To assess the antibody response to EDI200 [ Time Frame: Up to 6 months after dosing ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the pharmacodynamics/efficacy (growth and development) of EDI200 [ Time Frame: Baseline and 2, 4 and 6 months ] [ Designated as safety issue: No ]
  • To assess the pharmacodynamics/efficacy (dentition) of EDI200 [ Time Frame: Baseline and post-six months (extension study) ] [ Designated as safety issue: No ]
  • To assess the pharmacodynamics/efficacy (craniofacial development) of EDI200 [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
  • To assess the pharmacodynamics/efficacy (sweat duct density) of EDI200 [ Time Frame: Baseline and 2 and 6 months ] [ Designated as safety issue: No ]
  • To assess the pharmacodynamics/efficacy (sweat rate) of EDI200 [ Time Frame: Baseline and 2 and 6 months ] [ Designated as safety issue: No ]
  • To assess the pharmacodynamics/efficacy (Dry eye signs and symptoms) of EDI200 [ Time Frame: Baseline and 2 and 6 months ] [ Designated as safety issue: No ]
  • To assess the pharmacodynamics/efficacy (thermoregulation) of EDI200 [ Time Frame: Baseline and study day 21 ] [ Designated as safety issue: No ]
  • To assess the pharmacodynamics/efficacy (molecular expression profile of skin biopsy tissue) of EDI200 [ Time Frame: Baseline, study days 1 and 15 ] [ Designated as safety issue: No ]

Estimated Enrollment: 6
Study Start Date: April 2013
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   up to 14 Days
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01775462

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

Additional Information:
Responsible Party: Edimer Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01775462     History of Changes
Other Study ID Numbers: ECP-002 
Study First Received: January 17, 2013
Last Updated: January 19, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Edimer Pharmaceuticals:
Hypohidrotic Ectodermal Dysplasia
XLHED

Additional relevant MeSH terms:
Ectodermal Dysplasia
Ectodermal Dysplasia 1, Anhidrotic
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Skin Abnormalities
Skin Diseases
Skin Diseases, Genetic

ClinicalTrials.gov processed this record on April 27, 2016