A Phase 1, Open-label, Multicenter, Safety and Pharmacokinetic Study of EDI200

A Phase 1, Open-label, Multicenter, Safety and Pharmacokinetic Study of EDI200, an Ectodysplasin-A1 Replacement Molecule, in X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) Adults

Following discussions with the FDA, a Phase 1 safety study is being initiated in X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)-affected adults to develop safety and exposure data for EDI200 in anticipation of dosing XLHED-affected neonates. Selecting XLHED-affected adults for this study provides a genetic match and biologic relevance to XLHED-affected neonates. Both males and females will be enrolled, providing safety experience with EDI200 that will inform the planned neonate study as well as supportive data for potential future trials of antenatal EDI200 administration.

Study Overview

• Status: Completed
• Conditions: X-linked Hypohidrotic Ectodermal Dysplasia
• Intervention / Treatment: Drug: EDI200

Detailed Description

The Phase 1 study will enroll two cohorts of 3 XLHED-affected adults each, for a total of 6 subjects. The size and scope of the study design are consistent with a drug development program in an ultra-rare disease and supported by the absence of safety concerns in a GLP non-human primate toxicology study. All subjects must meet entry criteria including documentation of an EDA mutation. Mirroring the conditions of use anticipated for the XLHED-affected newborn study, the adult cohort study incorporates a multiple-dose regimen associated with maximal efficacy in the newborn canine model. Primary outcome measures will be safety, tolerability, immunogenicity and pharmacokinetics (PK). While current data does not support a likelihood of clinical benefit for the XLHED-affected adult subjects, assays of pharmacodynamic/biologic activity are incorporated into the study design as exploratory objectives.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Ohio
    • Cincinnati, Ohio, United States, 45226
      • Community Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females of child-bearing age, age 18-40 years
2. Weight between 45 and 90 kg and a body mass index (BMI) from 18 to 29 kg/m2 (calculated using the following formula: weight in kilograms/(height in meters)2)
3. Both males and females must be documented (via genetic testing) to carry an EDA mutation associated with XLHED; or have the clinical signs and symptoms associated with HED and/or a family history of HED and provide a blood sample to be sent for genetic testing that confirms an EDA mutation associated with XLHED
4. No major medical issues that the investigator considers to be a contraindication of participation
5. No scalp shaving in the month prior to first dose (males only)
6. Women must use a "highly effective" method of contraception throughout the trial. Highly effective methods of birth control are defined as those, alone or in combination, which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. These methods include implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation or a vasectomized partner.
7. No treatment with an investigational drug within the last three months
8. Signed written informed consent

Exclusion Criteria:

1. Women who are pregnant (confirmed via urine pregnancy test) or breastfeeding at screening or planning to become pregnant at any time during the study period
2. Known history of hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody
3. Known history of HIV infection
4. Known hypersensitivity to pilocarpine or pilocarpine-like muscarinic agonists
5. Known hypersensitivity to lidocaine or lidocaine-like agents
6. Presence of pacemakers
7. Subjects who are not able or are not willing to comply with the procedures of this protocol
8. Subject has a condition which in the opinion of the investigator would not allow for safe conduct of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EDI200	Drug: EDI200; Cohort 1 will be dosed at 3 mg/kg/dose. Cohort 2 will be dosed at 10 mg/kg/dose. Both cohorts will receive 2 doses/week for a total of 5 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events	Up to 42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory endpoint: change from baseline in biological activity	Hair number and growth properties; Pulmonary function and eNO levels; Sweat duct density; Sweat rate; Saliva quantitation; Tearing and dry eye evaluation; Skin biopsy for expression profile	Baseline and 42 days

Collaborators and Investigators

• Sponsor: Edimer Pharmaceuticals
• Investigators: Principal Investigator: Ophir Klein, MD, PhD, University of California, San Francisco; Principal Investigator: James Maynard, MD, Community Research

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: March 23, 2012
• First Submitted That Met QC Criteria: March 26, 2012
• First Posted (Estimate): March 27, 2012

Study Record Updates

• Last Update Posted (Estimate): November 27, 2013
• Last Update Submitted That Met QC Criteria: November 25, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: XLHED
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Skin Diseases, Genetic; Skin Abnormalities; Abnormalities, Multiple; Ectodermal Dysplasia; Ectodermal Dysplasia 1, Anhidrotic
• Other Study ID Numbers: ECP-004