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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Infant

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.

Detailed 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 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.
Sponsor: Edimer Pharmaceuticals

Current Primary Outcome:

  • Incidence and severity of adverse events [ Time Frame: Up to 6 months after dosing ]
  • To assess the antibody response to EDI200 [ Time Frame: Up to 6 months after dosing ]
  • 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 ]
  • 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 ]
  • 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 ]


Original Primary Outcome:

  • Incidence and severity of adverse events [ Time Frame: Up to 6 months after dosing ]
    To assess the safety and tolerability EDI200 administered to XLHED-affected neonates
  • To assess the antibody response to EDI200 [ Time Frame: Up to 6 months after dosing ]
    To assess the immunogenicity of EDI200 administered to XLHED-affected neonates
  • Area under the concentration time curve to the end of the dosing period (AUC0-tau) of EDI200 [ Time Frame: Pre-dose and 1, 4, 8, 24, 48 and 72 hours post-dose 1 and 5 ]
    To assess the pharmacokinetics of EDI200 administered to XLHED-affected neonates
  • Peak plasma concentration (Cmax) of EDI200 [ Time Frame: Pre-dose and 1, 4, 8, 24, 48 and 72 hours post-dose 1 and 5 ]
    To assess the pharmacokinetics of EDI200 administered to XLHED-affected neonates
  • Time at which maximum concentration is observed (Tmax) of EDI200 [ Time Frame: Pre-dose and 1, 4, 8, 24, 48 and 72 hours post-dose 1 and 5 ]
    To assess the pharmacokinetics of EDI200 administered to XLHED-affected neonates


Current Secondary Outcome:

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


Original Secondary Outcome:

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


Information By: Edimer Pharmaceuticals

Dates:
Date Received: January 17, 2013
Date Started: April 2013
Date Completion:
Last Updated: January 19, 2016
Last Verified: January 2016