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

Phase 2

Active, not recruiting

• Conditions: Hereditary Neuropathy Caused by SORD Deficiency
• Interventions: Drug: Placebo; Drug: AT-007

• Registration Number: NCT05397665
• Lead Sponsor: Applied Therapeutics, Inc.

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 patients for 24 months.

Detailed Description

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.

Study Timeline

• Study Start: 2022-01-01
• Study First Submitted: 2022-05-23
• Study First Submitted QC: 2022-05-26
• Study First Posted: 2022-05-31
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-22
• Last Update Posted: 2023-09-25
• Primary Completion: 2024-07-31
• Study Completion: 2026-07-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Is an non-active control
AT-007	AT-007	AT-007 is an Aldose reductase inhibitor

Primary Outcome Measures

Name	Time	Method
blood sorbitol levels	Baseline and up to month 24	Patients with SORD Deficiency are unable to metabolize sorbitol. All patients with SORD Deficiency have highly elevated levels of blood sorbitol.; The measurement of Sorbitol will provide evidence of the efficacy of the treatment (AT-007) used in the study
Muscle MRI (Magnetic Resonance Imaging)	Baseline and up to month 24 month	Patients will undergo MRI of their legs to evaluate the fat deposition and the muscle size.
10-meter walk-run test (10MWRT).	baseline and up to month 24	The 10MWRT measures the time necessary to walk or run a distance of 10 meters by the study population
CMT-Fom (Charcot Marie Tooth Functional Outcome Measure)	Baseline and up to month 24	The CMT-Fom is a performance-based assessment that measures the functional ability of patients with neuropathies

Trial Locations

Locations (10)

University of Rochester; 🇺🇸 Rochester, New York, United States

University of Miami; 🇺🇸 Coral Gables, Florida, United States

Fondazione IRCCS Istituto Neurologico "Carlo Besta"; 🇮🇹 Milano, Italy

Axon Clinical, s.r.o.; 🇨🇿 Prague, Czechia

Hassman Research Institute; 🇺🇸 Berlin, New Jersey, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University College of London; 🇬🇧 London, United Kingdom