A Multi-center, Randomized, Double-blind, Placebo Controlled Phase III Study to Assess the Efficacy, Safety, and Tolerability of PXT3003 in Charcot-Marie-Tooth Type 1A (CMT1A)

• Male and non-pregnant female subjects, aged 16 to 65 years with a genetically proven diagnosis of CMT1A. Notes: a) A report of a genetic test confirming PMP22 duplication and therefore a diagnosis of CMT1A must be available in the subject's record at the clinical site. b) In the absence of a report of a genetic test confirming PMP22 duplication in the subject's medical record, a confirmatory genetic test must be conducted via the central laboratory as part of Screening. c) In the exceptional case wherein subject was randomized into the study without meeting(a) or (b), an unscheduled confirmatory genetic test will be performed. In the event of a negative genetic test result, the subject will be withdrawn from the study.

• Able to provide written informed consent/assent and comply with study procedures.

• Mild-to-moderate severity assessed by a CMTNS-V2 score \>2 and ≤18.

• Muscle weakness in at least foot dorsiflexion on clinical assessment.

• Ulnar nerve motor conduction time of at least 15 m/s.

• If taking prescribed psychoactive drugs(eg, antidepressants, stimulants, tranquilizers, anti-epileptics) for CMT1A, should be on a stable dose for at least 4 weeks prior to randomization, which is not planned to be changed.

• If taking prescribed or 'over-the-counter' analgesic medications (eg, paracetamol/acetaminophen, nonsteroidal anti-inflammatory drugs) for CMT1A, should be on a stable dose for at least 2 weeks prior to randomization, which is not planned to be changed.

• If female, subject must be: (a) surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or (b) of childbearing potential and using a birth control method such as:

‣ Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

• Oral

∙ Intravaginal

∙ Transdermal

⁃ Progestogen-only hormonal contraception associated with inhibition of ovulation:

• Oral

∙ Injectable

∙ Implantable

⁃ Intrauterine device

⁃ Intrauterine hormone-releasing system

⁃ Bilateral tubal occlusion

⁃ Vasectomized partner

⁃ Sexual abstinence or (c) Of non-childbearing potential (i.e., no menses for ≥ 12 consecutive months without any other underlying medical cause)

• If male, the subject must have had a vasectomy or must use a reliable method of birth control with their partner or total abstinence from sexual intercourse. The subject must agree to continue using their selected method of birth control with their sexual partner during the study and for 120 days after study completion.

• Able to provide written informed consent/assent and comply with study procedures.

• If female, subject must be (a) surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or (b) of childbearing potential and using a birth control method such as:

‣ Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

• Oral

∙ Intravaginal

∙ Transdermal

⁃ Progestogen-only hormonal contraception associated with inhibition of ovulation:

• Oral

∙ Injectable

∙ Implantable

⁃ IUD

⁃ IUS

⁃ Bilateral tubal occlusion

⁃ Vasectomized partner

⁃ Sexual abstinence or (c) of non-childbearing potential (ie, no menses for ≥12 consecutive months without any other underlying medical cause).

• If male, the subject must have had a vasectomy or must use a reliable method of birth control with their partner or total abstinence from sexual intercourse. The subject must agree to continue using their selected method of birth control with their sexual partner during the study and for 120 days after study completion.