Pharmacodynamic EffIcacy and Clinical Benefit of AT 007 in Patients With Sorbitol Dehydrogenase (SORD) Deficiency

This study is designed to assess the efficacy and safety of AT-007 treatment in patients with SORD Deficiency. This randomized, double-blind study will assess the effect of AT-007 compared to Placebo in SORD Deficiency patients for 24 months.

This international, multi-center, randomized, double-blinded, placebo-controlled, phase 2-3 study is designed to assess the pharmacodynamic (PD) efficacy and clinical benefit of long term administration of AT 007 versus placebo in male and non-pregnant female subjects with genetically confirmed SORD Deficiency aged 18-55 and able to ambulate with a 10MWRT time of \<10 seconds.

The study will be conducted at up to 12 sites worldwide. Genetically confirmed SORD Deficiency patients with blood sorbitol levels \>10,000 ng/ml will be screened and randomized in a 2:1 ratio to receive either AT-007 daily or a matching placebo for 24 months. A total of up to 72 subjects will be enrolled.

The primary clinical outcome measure, 10-meter walk-run test (10MWRT), will be assessed at 24 months and compared to baseline.

Eligibility Criteria:
1. Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.
2. Male and non-pregnant, non-lactating female patients between the ages of 18 and 55 years, inclusive.
3. Females must be of non-childbearing potential (defined as surgically sterile \[i.e., had a bilateral tubal ligation, hysterectomy, or bilateral oophorectomy ≥6 months prior to the first dose of study drug\] or postmenopausal for ≥1 year \[confirmatory follicle stimulating hormone or FSH test results required\] prior to the first dose of study drug) or agree to use an acceptable form of birth control from Screening until 30 days after the last dose of study drug.
4. Males must be unable to procreate (defined as surgically sterile \[i.e., had a vasectomy ≥6 months prior to Screening\]) or must agree to use an acceptable form of birth control from Screening through 30 days after the last dose of study drug.
5. Clinical diagnosis of CMT2 or dHMN due to SORD Deficiency confirmed by medical record or written communication by health care professional, elevated sorbitol level (\>10,000 ng/mL), and gene analysis report indicating a biallelic mutation in SORD.

Exclusion Criteria:

1. 10MWRT classified as very severe disease (e.g. 10MWRT \>10 seconds to complete).
2. History or presence of clinically significant hematopoietic, renal, hepatic, endocrine (e.g. diabetes), metabolic, pulmonary, neurological (e.g. other neuropathy, myopathy or neuromuscular disorder), psychiatric, cardiovascular, immunological, dermatological, or gastrointestinal diseases that are -at priori- altering the proper evaluation of the safety and efficacy of AT-007; conditions capable of altering the absorption, metabolism, or elimination of drugs; or conditions that constitute a risk factor when taking the study drug and/or impact the conduct or results of the study.
3. Body Mass Index (BMI) \>35 kg/m2 or clinically relevant underweight, weight loss suggestive of a pathology unrelated to SORD deficiency, or BMI \< 17.5 kg/m2.
4. Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) at Screening or previous treatment for hepatitis B, hepatitis C, or HIV infection.
5. Individuals who smoke or use tobacco or nicotine-containing products. Any prior history of substance abuse.
6. Pregnant, lactating, or not using/not willing to use appropriate means of contraception.
7. Non-ambulatory disability.
8. Prior bilateral ankle stabilization surgery.
9. Evidence of significant active hematological disease and/or cumulative blood donation of 1 unit (500 mL) or more including blood drawn during clinical studies in the last 3 months.
10. History of significant drug allergy or drug hypersensitivity.
11. Participation in another clinical study of a different investigational product within 30 days prior to the first dose of study drug.
12. Use of any prescription medication that is likely to interfere with the study drug.