First human testing of EDK060 in adults with CMT1A.

A First-in-human, Multi-center, Randomized, Participant- and Investigator-blinded, Placebo Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of EDK060 in Adults With Charcot-Marie Tooth Type 1A (CMT1A).

This trial will test whether different doses of the experimental drug EDK060 are safe and how the body processes them in adults with CMT1A.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Locations: 3 sites (Ottawa, Ontario and 2 other locations)
• Trial ID: NCT07140614 on ClinicalTrials.gov

What this trial studies

This is a first-in-human Phase 1 interventional study in which adults with genetically confirmed CMT1A will receive one of four doses of EDK060 or placebo. Participants will be monitored closely for safety, tolerability, and pharmacokinetics after dosing and followed for adverse events and selected neurological measures. Key eligibility includes age 18–60, PMP22 gene duplication, measurable nerve conduction, a CMTNSv2R score >2 and ≤20, and foot dorsiflexion weakness. The trial is sponsored by Novartis and conducted at sites in Ottawa, Montreal, and Sherbrooke.

Who should consider this trial

Good fit: Adults 18 to 60 with genetically confirmed PMP22 duplication, detectable nerve conduction, CMTNSv2R >2 and ≤20, and foot dorsiflexion weakness who can give informed consent and attend study visits are the intended participants.

Not a fit: People under 18, those without a confirmed PMP22 duplication, those with disease severity outside the inclusion ranges, or those unable to travel to the study sites are unlikely to benefit from or be eligible for this trial.

Why it matters

Potential benefit: If EDK060 is safe and shows favorable pharmacokinetics, it could lead to a new therapy that improves nerve function or symptoms for people with CMT1A.

How similar studies have performed: Other experimental therapies targeting PMP22 for CMT1A have shown early promise in preclinical and some clinical work, but first-in-human testing of EDK060 is a novel step.

Eligibility criteria

Inclusion Criteria:

* Provide written informed consent before any assessment is performed.
* Be male or female and 18 to 60 (inclusive) years of age at the time of screening.
* Participant must have a clinical diagnosis of Charcot-Marie-Tooth Disease Type 1A (CMT1A) including verified documentation of genetic testing showing duplication of the PMP22 gene by an accredited/certified laboratory (according to local regulations)
* Have detectable upper extremity nerve conduction velocities (sensory and/or motor) in at least one extremity at screening.
* CMTNSv2R score \>2 and ≤20 in at least one assessment, confirmed either at the baseline visit or documented in the medical record within the 6 months prior to baseline.
* Muscle weakness evidenced by foot dorsiflexion MRC grade \<5 in at least one limb, confirmed either at screening assessment or documented in the medical record within the 6 months prior to screening.

Exclusion Criteria

* Unable to communicate well with the investigator, to understand and comply with the visits and procedures of the study.
* History of cardiac, renal, liver, hematological, immune system disorders.
* Pregnant/nursing female participants. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for the duration of the follow-up period. Sexually active males unless they use a condom during intercourse.
* Inability or unwillingness to provide serial skin biopsy samples.
* Inability or unwillingness to undergo repeated venipuncture or in the opinion of the investigator, participant would be at an increased risk for adverse events related to these procedures.
* Use of any drug intended to modify the course of CMT1A within 6 months from screening, including but not limited to: PTX-3003 (baclofen, sorbitol, and naltrexone in combination).
* History of compression neuropathy within the last 6 months from screening and/or other conditions that can cause peripheral neuropathy, including but not limited to diabetes, chronic alcoholism, exposure to neurotoxic medications, exposure to environmental neurotoxins, traumatic nerve injury, thyroid disease, or infections.

Other protocol-defined inclusion/exclusion criteria may apply

Where this trial is running

Ottawa, Ontario and 2 other locations

• The Ottawa Hospital — Ottawa, Ontario, Canada (Recruiting)
• Montreal Neurological Institute — Montreal, Quebec, Canada (Recruiting)
• CIUSS de l´Estrie-CHUS- Hôpital Fleurimont — Sherbrooke, Quebec, Canada (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Charcot-Marie-Tooth Disease, Type 1A; CMT1A