Confirmatory Study of Govorestat in CMT-SORD

NCT07191912 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AT-007-1020
• Study Type: interventional
• Target: 155
• Locations: 7 countries
• Sites: 13

Brief Summary

This study is designed to assess the long-term efficacy and clinical benefit of AT-007 in patients with CMT-SORD. This randomized, double-blind study will assess the effect of govorestat compared to placebo in patients with CMT-SORD for up to 36 months.

Conditions

Charcot-Marie-Tooth Disease With Sorbitol Dehydrogenase Deficiency (CMT-SORD)

Outcome Measures

Primary Outcomes (1)

• Charcot-Marie-Tooth, Health Index (CMT-HI) Total Score

  The CMT-HI is a disease-specific, validated, patient-reported measure that is largely focused on functional items in addition to activities of daily living and emotional well-being. The CMT-HI was designed to assess specific impact of CMT disease and to remove redundancy.

  From enrollment to the end of treatment at 36 months

Secondary Outcomes (7)

• 10-meter walk-run test (10MWRT)

  From enrollment to the end of treatment at 36 months

• Dorsiflexion

  From enrollment to the end of treatment at 36 months

• Charcot-Marie-Tooth, Health Index (CMT-HI) Sub-Domain Scores

  From enrollment to the end of treatment at 36 months

• Charcot Marie Tooth Functional Outcome Measure (CMT-FOM)

  From enrollment to the end of treatment at 36 months

• Muscle Magnetic Resonance Imaging (MRI)

  From enrollment to the end of treatment at 36 months

Study Arms (2)

Govorestat

ACTIVE COMPARATOR

Govorestat is an aldose reductase inhibitor

Drug: Govorestat

Placebo

PLACEBO COMPARATOR

Non-active control

Drug: Placebo Control

Interventions

Govorestat DRUG

Govorestat will be provided as a liquid suspension (200mg/mL) for weight-based administration and administered orally at 20 mg/kg QD (every 24 hours)

Also known as: AT-007

Govorestat

Placebo Control DRUG

Placebo will also be provided as a matching liquid suspension to be taken orally QD

Placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male and non-pregnant, non-lactating female patients between the ages of 16 and 65 years, inclusive.
• 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 a highly effective form of birth control from Screening until 30 days after the last dose of study drug.
• 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 a highly effective form of birth control from Screening through 105 days (sum of 5 half-lives and 90 days interval as per CTFG guidelines) after the last dose of study drug.
• Clinical diagnosis of Charcot-Marie-Tooth Type 2 (CMT2) or distal Hereditary Motor Neuropathy (dHMN) due to CMT-SORD confirmed by medical record or written communication by health care professional, elevated blood sorbitol level (\>10,000 ng/mL), and SORD gene analysis report indicating at least one pathogenic mutation.
• Patient may be on concomitant medications and dietary supplements; however, they must be on stable doses for at least 1 month prior to Screening and throughout the study. In addition, all over-the-counter (OTC) and/or prescription medications must be reviewed and approved by the Investigator.

You may not qualify if:

• Absence of force generated in one or both feet with dorsiflexion (value of 0 Newton).
• 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 - a priori - altering the proper evaluation of the safety and efficacy of govorestat; 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.
• Body Mass Index (BMI) \>35 kg/m2.
• Clinically relevant underweight, weight loss suggestive of a pathology unrelated to CMT-SORD, or BMI \< 17.5 kg/m2.
• 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.
• Individuals who smoke or use tobacco or nicotine-containing products.
• Pregnant, lactating, or not using/not willing to use appropriate means of contraception.
• Any prior history of substance abuse (including alcohol) or treatment for such.
• Positive urine drug screen (UDS) for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, opiates) or cotinine.
• Non-ambulatory disability.
• Lower limb surgery such as bilateral ankle stabilization or contracture release in the past 5 years.
• Impaired renal function or estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m2. Note: The eGFR is an estimation of renal function, and the ultimate decision of whether a patient has normal renal function (and can be included in the study) is at the discretion of the Investigator, assuming there are no safety concerns. Also, because eGFR can vary from day to day based on outside factors, patients can be re screened for eGFR multiple times to understand the renal function of the patient.
• Hemoglobin (Hgb) \< 10.0 g/dL at Screening.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin (except in case of Gilbert's syndrome) \> 1.5 x upper limit of normal (ULN) at Screening.
• Urinary albumin-to-creatinine ratio (UACR) \> 30 mg/g at Screening in the presence of elevated creatinine (\>2X ULN).

Sponsors & Collaborators

• Applied Therapeutics, Inc.: lead

Study Sites (13)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Clinic for Special Children

Gordonville, Pennsylvania, 17529, United States

Location

Sydney Childrens

Sydney, 2013, Australia

Location

CHU La Timone

Marseille, 13005, France

Location

Institut de Myologie

Paris, 75013, France

Location

Uniklinik of the RWTH Aachen University

Aachen, 52074, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

University Medicine Gottingen (UMG)

Göttingen, 37075, Germany

Location

Carlo Besta Neurological Institute

Milan, 20133, Italy

Location

Vall d'Hebron Institut de Recerca (VHIR)

Barcelona, 08035, Spain

Location

La Fe University and Polytechnic Hospital

Valencia, 46026, Spain

Location

Koç University Hospital

Istanbul, 34010, Turkey (Türkiye)

Location

Istanbul University

Istanbul, 34093, Turkey (Türkiye)

Location

Central Study Contacts

Evan Bailey, MD

CONTACT

212-220-9226; Ebailey@appliedtherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Govorestat and its matching placebo will have the same presentation, the same aspect and taste in order to be indistinguishable, and they will be supplied and used in the same conditions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind study

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: September 25, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); IT (1); ES (2); TU (2); DE (3); FR (2); AU (1)