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

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.

Inclusion criteria

• Males and females of child-bearing age, age 18-40 years
• 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)
• 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
• No major medical issues that the investigator considers to be a contraindication of participation
• No scalp shaving in the month prior to first dose (males only)
• 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.
• No treatment with an investigational drug within the last three months
• Signed written informed consent

Exclusion criteria

• 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
• Known history of hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody
• Known history of HIV infection
• Known hypersensitivity to pilocarpine or pilocarpine-like muscarinic agonists
• Known hypersensitivity to lidocaine or lidocaine-like agents
• Presence of pacemakers
• 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