Phase 2 Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics/Efficacy of EDI200 in Male Infants With X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) (ECP-002)
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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 and Pharmacodynamics/Efficacy of EDI200, an EDA-A1 Replacement Protein, Administered to Male Infants With X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) |
- 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 1, 4, 8, 24, 48 and 72 hours post-dose 1 and 5 ] [ Designated as safety issue: Yes ]
- Peak plasma concentration (Cmax) of EDI200 [ Time Frame: Pre-dose and 1, 4, 8, 24, 48 and 72 hours post-dose 1 and 5 ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: Yes ]
- 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 15 ] [ 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 and 6 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 6 |
| Study Start Date: | April 2013 |
| Estimated Study Completion Date: | October 2014 |
| Estimated Primary Completion Date: | October 2014 (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 |
Inclusion Criteria:
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.
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:
- 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.
Contacts and Locations| Contact: Ramsey Johnson, MSM | 617-758-4305 | ramsey@edimerpharma.com |
| United States, Missouri | |
| Washington University School of Medicine | Not yet recruiting |
| St. Louis, Missouri, United States, 63110 | |
| Contact: Dorothy Grange, MD 314-454-6093 grange_d@kids.wustl.edu | |
| Contact: , MD | |
| Germany | |
| University Hospital Erlangen | Not yet recruiting |
| Erlangen, Bavaria, Germany, 91054 | |
| Contact: Holm Schneider, MD, PhD +49 9131 8533775 Holm.Schneider@uk-erlangen.de | |
| Study Director: | Kenneth Huttner, MD, PhD | Edimer Pharmaceuticals |
More Information
Additional Information:
No publications provided
| 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 28, 2013 |
| 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 Hyperplasia Abnormalities, Multiple Congenital Abnormalities Skin Abnormalities |
Skin Diseases, Genetic Genetic Diseases, Inborn Skin Diseases Genetic Diseases, X-Linked Pathologic Processes |
ClinicalTrials.gov processed this record on May 16, 2013