Clinical trial NCT01775462: Phase 2 Study to Evaluate Safety, Pharmacokinetics, Immunogenicity and Pharmacodynamics/Efficacy of EDI200 in Male Infants With X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: X-Linked Hypohidrotic Ectodermal Dysplasia
Keywords: Hypohidrotic Ectodermal Dysplasia
XLHED
Lead sponsor: Edimer Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-01-25
Enrollment: 6
Sex: MALE
Minimum age (years): 48
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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 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.

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: Up to 6 months after dosing
measure: To assess the antibody response to EDI200
timeFrame: Up to 6 months after dosing
measure: Area under the concentration time curve to the end of the dosing period (AUC0-tau) of EDI200
timeFrame: 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
measure: Peak plasma concentration (Cmax) of EDI200
timeFrame: 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
measure: Time at which maximum concentration is observed (Tmax) of EDI200
timeFrame: 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:
measure: To assess the pharmacodynamics/efficacy (growth and development) of EDI200
timeFrame: Baseline and 2, 4 and 6 months
measure: To assess the pharmacodynamics/efficacy (dentition) of EDI200
timeFrame: Baseline and post-six months (extension study)
measure: To assess the pharmacodynamics/efficacy (craniofacial development) of EDI200
timeFrame: Baseline and 6 months
measure: To assess the pharmacodynamics/efficacy (sweat duct density) of EDI200
timeFrame: Baseline and 2 and 6 months
measure: To assess the pharmacodynamics/efficacy (sweat rate) of EDI200
timeFrame: Baseline and 2 and 6 months
measure: To assess the pharmacodynamics/efficacy (Dry eye signs and symptoms) of EDI200
timeFrame: Baseline and 2 and 6 months
measure: To assess the pharmacodynamics/efficacy (thermoregulation) of EDI200
timeFrame: Baseline and study day 21
measure: To assess the pharmacodynamics/efficacy (molecular expression profile of skin biopsy tissue) of EDI200
timeFrame: Baseline, study days 1 and 15
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Erlangen
country: Germany
facility: University Hospital Erlangen
state: Bavaria
city: Milan
country: Italy
facility: Azienda Ospedaliera-Polo Universitario "Luigi Sacco"
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
Study officials:
affiliation: Edimer Pharmaceuticals
name: Kenneth Huttner, MD, PhD
role: STUDY_DIRECTOR
References: