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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)

Primary Purpose

X-Linked Hypohidrotic Ectodermal Dysplasia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

EDI200

About this trial

This is an interventional treatment trial for X-Linked Hypohidrotic Ectodermal Dysplasia focused on measuring Hypohidrotic Ectodermal Dysplasia, XLHED

Eligibility Criteria

48 Hours - 14 Days (Child)MaleDoes not accept healthy volunteers

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.

Sites / Locations

University of California, San Francisco
Children's National Medical Center
Washington University School of Medicine
Hôpital Necker-Enfants Malades
University Hospital Erlangen
Azienda Ospedaliera-Polo Universitario "Luigi Sacco"
University Hospital of Wales

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

EDI200, 3mg/kg

EDI200, 10 mg/kg

Arm Description

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

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

Outcomes

Primary Outcome Measures

Incidence and severity of adverse events

To assess the antibody response to EDI200

Area under the concentration time curve to the end of the dosing period (AUC0-tau) of EDI200

Peak plasma concentration (Cmax) of EDI200

Time at which maximum concentration is observed (Tmax) of EDI200

Secondary Outcome Measures

To assess the pharmacodynamics/efficacy (growth and development) of EDI200

To assess the pharmacodynamics/efficacy (dentition) of EDI200

To assess the pharmacodynamics/efficacy (craniofacial development) of EDI200

To assess the pharmacodynamics/efficacy (sweat duct density) of EDI200

To assess the pharmacodynamics/efficacy (sweat rate) of EDI200

To assess the pharmacodynamics/efficacy (Dry eye signs and symptoms) of EDI200

To assess the pharmacodynamics/efficacy (thermoregulation) of EDI200

To assess the pharmacodynamics/efficacy (molecular expression profile of skin biopsy tissue) of EDI200

Full Information

NCT ID

NCT01775462

First Posted

January 17, 2013

Last Updated

January 19, 2016

Sponsor

Edimer Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01775462

Brief Title

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

Acronym

ECP-002

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

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Completed

Study Start Date

April 2013 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Edimer Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

X-Linked Hypohidrotic Ectodermal Dysplasia

Keywords

Hypohidrotic Ectodermal Dysplasia, XLHED

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

EDI200, 3mg/kg

Arm Type

Experimental

Arm Description

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

Arm Title

EDI200, 10 mg/kg

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

EDI200

Other Intervention Name(s)

APO200

Intervention Description

3 or 10 mg/kg of EDI200

Primary Outcome Measure Information:

Title

Incidence and severity of adverse events

Time Frame

Up to 6 months after dosing

Title

To assess the antibody response to EDI200

Time Frame

Up to 6 months after dosing

Title

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

Title

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

Title

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

Secondary Outcome Measure Information:

Title

To assess the pharmacodynamics/efficacy (growth and development) of EDI200

Time Frame

Baseline and 2, 4 and 6 months

Title

To assess the pharmacodynamics/efficacy (dentition) of EDI200

Time Frame

Baseline and post-six months (extension study)

Title

To assess the pharmacodynamics/efficacy (craniofacial development) of EDI200

Time Frame

Baseline and 6 months

Title

To assess the pharmacodynamics/efficacy (sweat duct density) of EDI200

Time Frame

Baseline and 2 and 6 months

Title

To assess the pharmacodynamics/efficacy (sweat rate) of EDI200

Time Frame

Baseline and 2 and 6 months

Title

To assess the pharmacodynamics/efficacy (Dry eye signs and symptoms) of EDI200

Time Frame

Baseline and 2 and 6 months

Title

To assess the pharmacodynamics/efficacy (thermoregulation) of EDI200

Time Frame

Baseline and study day 21

Title

To assess the pharmacodynamics/efficacy (molecular expression profile of skin biopsy tissue) of EDI200

Time Frame

Baseline, study days 1 and 15

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

48 Hours

Maximum Age & Unit of Time

14 Days

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kenneth Huttner, MD, PhD

Organizational Affiliation

Edimer Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

Children's National Medical Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20010

Country

United States

Facility Name

Washington University School of Medicine

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Hôpital Necker-Enfants Malades

City

Paris

ZIP/Postal Code

75015

Country

France

Facility Name

University Hospital Erlangen

City

Erlangen

State/Province

Bavaria

ZIP/Postal Code

91054

Country

Germany

Facility Name

Azienda Ospedaliera-Polo Universitario "Luigi Sacco"

City

Milan

ZIP/Postal Code

20157

Country

Italy

Facility Name

University Hospital of Wales

City

Cardiff

ZIP/Postal Code

CF14 4XW

Country

United Kingdom

12. IPD Sharing Statement

Links:

URL

http://www.edimerpharma.com

Description

Sponsor's website

Learn more about this trial

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

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