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

NCT05397665 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AT-007-1005
• Study Type: interventional
• Target: 56
• Locations: 4 countries
• Sites: 10

Brief Summary

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 in patients for up to 24 months.

Conditions

Hereditary Neuropathy Caused by SORD Deficiency

Outcome Measures

Primary Outcomes (2)

• 10-meter walk-run test (10MWRT).

  The 10MWRT is a timed functional test used to measure walking or running speed over 10 meters by the study population

  baseline and up to month 24

• Blood sorbitol levels

  Patients with SORD Deficiency develop extremely high sorbitol levels in cells and tissues, as aldose reductase converts glucose to sorbitol which then cannot be converted into fructose by SORD. Sorbitol is known to be toxic to many cell types. The measurement of change in sorbitol will provide evidence of the efficacy of the treatment (AT-007) used in the study.

  Baseline and up to 3 months.

Secondary Outcomes (5)

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

  Baseline and up to month 24

• Charcot Marie Tooth Health Index (CMTHI)

  Baseline and up to month 24

• Exit Interview

  To be completed at month 24

• Muscle Magnetic Resonance Imaging (MRI)

  Baseline and up to month 24 month

• Blood Sorbitol Levels and Correlation with Clinical Outcomes

  Baseline and up to month 24

Study Arms (2)

AT-007

ACTIVE COMPARATOR

AT-007 is an Aldose reductase inhibitor

Drug: AT-007

Placebo

SHAM COMPARATOR

Is an non-active control

Drug: Placebo

Interventions

AT-007 DRUG

AT-007, aldose reductase inhibitor

Also known as: Govorestat

AT-007

Placebo DRUG

Liquid oral suspension

Also known as: Liquid oral vehicle suspension

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

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 18 and 55 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 an acceptable 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 an acceptable form of birth control from Screening through 30 days after the last dose of study drug.
• 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.
• 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.
• Willing and able to be confined to the clinical research unit (CRU) as required by the protocol.

You may not qualify if:

• MWRT classified as very severe disease (e.g. 10MWRT \>15 seconds to complete OR unable to complete 10MWRT without the use of an assistive device such as a cane/walker/wheelchair).
• 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.
• Body Mass Index (BMI) \>35 kg/m2.
• Clinically relevant underweight, weight loss suggestive of a pathology unrelated to SORD deficiency, 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.
• Prior bilateral ankle stabilization surgery.
• 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 (10)

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Miami

Coral Gables, Florida, 33146, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Axon Clinical, s.r.o.

Prague, Prague, 150 00, Czechia

Location

Fondazione IRCCS Istituto Neurologico "Carlo Besta"

Milan, Milano, 20133, Italy

Location

University College of London

London, London, WC1E 6BT, United Kingdom

Location

Study Officials

• Michael E Shy, MD

  University of Iowa

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: AT-007 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: May 23, 2022
• First Posted: May 31, 2022
• Study Start: January 1, 2022
• Primary Completion: October 12, 2024
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); US (7); CZ (1); GB (1)