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

• ClinicalTrials.gov Identifier: NCT05397665
• Recruitment Status: Recruiting
• First Posted: May 31, 2022
• Last Update Posted: May 31, 2022
• Sponsor: Applied Therapeutics, Inc.
• Information provided by (Responsible Party): Applied Therapeutics, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hereditary Neuropathy Caused by SORD Deficiency	Drug: AT-007; Drug: Placebo	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double blind study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: 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.
• Primary Purpose: Treatment
• Official Title: A RandomIzed, Double-Blind, Placebo-CoNtrolled, Two-Part Study to Evaluate the Pharmacodynamic EffIcacy and Clinical Benefit of AT 007 in Patients With SoRbitol Dehydrogenase (SORD) DEficiency
• Actual Study Start Date: January 1, 2022
• Estimated Primary Completion Date: July 31, 2024
• Estimated Study Completion Date: July 31, 2026

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: AT-007; AT-007 is an Aldose reductase inhibitor	Drug: AT-007; AT-007, aldose reductase inhibitor; Other Name: Govorestat
Sham Comparator: Placebo; Is an non-active control	Drug: Placebo; Liquid oral suspension; Other Name: Liquid oral vehicle suspension

Outcome Measures

Primary Outcome Measures :

1. 10-meter walk-run test (10MWRT). [ Time Frame: 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
2. blood sorbitol levels [ Time Frame: 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

3. Muscle MRI (Magnetic Resonance Imaging) [ Time Frame: Baseline and up to month 24 month ]
   Patients will undergo MRI of their legs to evaluate the fat deposition and the muscle size.
4. CMT-Fom (Charcot Marie Tooth Functional Outcome Measure) [ Time Frame: Baseline and up to month 24 ]
   The CMT-Fom is a performance-based assessment that measures the functional ability of patients with neuropathies

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Contacts

Contact: Riccardo Perfetti, MD, PhD; 3477023018; rperfetti@appliedtherapeutics.com

Contact: Michael E Shy, MD; 319.356.7110; michael-shy@uiowa.edu

Locations

United States, New Jersey

Hassman Research Institute; Recruiting

Berlin, New Jersey, United States, 08009

Contact: Michael Hassman, MD 856-753-7355 ext 316 drmhassman@hritrials.com

Sponsors and Collaborators

Applied Therapeutics, Inc.

Investigators

• Study Chair: Michael E Shy, MD; University of Iowa

More Information

• Responsible Party: Applied Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05397665
• Other Study ID Numbers: AT-007-1005
• First Posted: May 31, 2022
• Last Update Posted: May 31, 2022
• Last Verified: May 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No