Hereditary Neuropathy Caused by SORD DeficiencyPhase 2/3INSPIRENCT05397665
Pharmacodynamic EffIcacy and Clinical Benefit of AT 007 in Patients With Sorbitol Dehydrogenase (SORD) Deficiency
A Phase 2/3 study testing AT-007 in people with Hereditary Neuropathy Caused by SORD Deficiency, run by Applied Therapeutics, Inc. at 10 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Hereditary Neuropathy Caused by SORD Deficiency
- What is being tested?
- AT-007
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 10 sitesin 4 countries
- Study dates
- 1 Jan 2022to 1 Jun 2026
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 10MWRT 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.
Show all 30Show fewer
- 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).
- History or presence of cardiovascular disorders including myocardial infarction, stroke, uncontrolled hypertension (sitting blood pressure ≥140/90 mmHg), left ventricular (LV) hypertrophy, atrial fibrillation, or valvular heart disease considered clinically significant by the Principal Investigator (PI) and/or Sponsor medical representative.
- Abnormal findings on the Screening 12-lead ECG, such as ST/T wave changes, pathological Q wave changes, or any rhythm other than normal sinus rhythm considered clinically significant by the PI and/or Sponsor medical representative.
- 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.
- History of significant drug allergy or drug hypersensitivity.
- Investigators, site personnel directly affiliated with this study, and their immediate families (defined as a spouse, parent, child, or sibling, whether biological or legally adopted).
- Any other condition that, in the opinion of the Investigator, precludes the patient from following and completing the protocol.
- A clinically significant abnormal finding on the physical exam/visual health assessment, medical history, ECG, or clinical laboratory results at Screening.
- A significantly abnormal diet (per Investigator judgment) during the 4 weeks preceding the first dose of study drug.
- Participation in another clinical study of a different investigational product within 30 days prior to the first dose of study drug.
- Use of any OTC medication (including nutritional or dietary supplements, herbal preparations, or vitamins) ≤7 days prior to the first dose of study drug until the last dose of study drug without evaluation and approval by the Investigator.
- Use of any prescription medication, except those allowed per protocol, from 30 days prior to the first dose of study drug until the last dose of study drug without evaluation and approval by the Investigator.
- Treatment with any sensitive substrates of Breast Cancer Resistance Protein (BCRP) or potent inhibitors of BCRP.
- Treatment with any sensitive substrates of cytochrome P450 3A4 (CYP3A4), CYP2B6, CYP2C19, or CYP1A2.
- Treatment with any sensitive substrates of Organic Anion Transporter (OAT)1 and OAT3. Treatment with any drugs potentially associated with transaminase elevations. Potentially nephrotoxic drugs are prohibited.
- Consumption of beverages or foods that contain alcohol, high levels of sorbitol, grapefruit, poppy seeds, broccoli, brussels sprouts, pomegranate, star fruit, char-grilled meat, or caffeine/xanthine from 48 hours prior to the first dose of study drug through the last dose of study drug. Patients will be instructed not to consume any of the above products; however, allowance for sporadic consumption may be evaluated and approved by the Investigator based on the potential for interaction with the study drug. Not more than half cup of coffee per day should be consumed.
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
United States7 sites
University of Colorado
Aurora, Colorado, 80045
Hassman Research Institute
Berlin, New Jersey, 08009
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Miami
Coral Gables, Florida, 33146
University of Iowa
Iowa City, Iowa, 52242
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Rochester
Rochester, New York, 14642
Italy1 site
Fondazione IRCCS Istituto Neurologico "Carlo Besta"
Milan, Milano, 20133
United Kingdom1 site
University College of London
London, London, WC1E 6BT
About this study
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
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.
Read the detailed description
This international, multi-center, randomized, double-blinded, placebo-controlled, phase 2-3 study is designed to assess the pharmacodynamic (PD) efficacy of AT-007 treatment, as well as the clinical benefit of long term administration to patients with SORD Deficiency utilizing a series of functional, patient-reported, and clinical outcomes measures.Safety and pharmacokinetics (PK) of AT-007 will also be evaluated. The study consists of Biomarker and Efficacy Assessments and an open-label extension (OLE) of active treatment for qualified patients.
Patients (18-55 years old) with SORD deficiency will be stratified according to their 10MWRT score (a single component of the CMT-FOM) and sex (male vs female). They will then be randomized in a 2:1 ratio to AT-007 20 mg/kg once daily (QD) or placebo.
The study will be conducted at up to 13 sites worldwide. A total of up to 72 subjects will be enrolled.
- Being tested
- AT-007, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT-007Drug
Also called Govorestat
AT-007, aldose reductase inhibitor
PlaceboDrug
Also called Liquid oral vehicle suspension
Liquid oral suspension
| Study group | Role | What they receive |
|---|---|---|
| AT-007 | Active comparator | AT-007 is an Aldose reductase inhibitor Receives: Drug: AT-007 |
| Placebo | Sham comparator | Is an non-active control Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: Baseline and up to 3 months.
Secondary outcomes (5)
Charcot Marie Tooth Functional Outcome Measure (CMT-FOM)
The CMT-Fom is a performance-based measure that assesses the functional ability of patients with CMT. Total and subdomain scores as well as individual components of the CMT-FOM, each as it's own secondary endpoint will be evaluated to detect change over time.
Measured: Baseline and up to month 24
Charcot Marie Tooth Health Index (CMTHI)
The CMTHI is a disease-specific patient reported outcome that assesses disease burden in the study population. This will be used to assess patient-detected disease burden over time.
Measured: Baseline and up to month 24
Exit Interview
A blinded assessment of the study population's perspective on the impact of disease on their lives and the benefit or perceived harm during the study.
Measured: To be completed at month 24
Muscle Magnetic Resonance Imaging (MRI)
Patients will undergo MRI of their legs to evaluate the fat deposition and the muscle size, both CMT-related parameters of disease progression.
Measured: Baseline and up to month 24 month
Blood Sorbitol Levels and Correlation with Clinical Outcomes
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. Longitudinal correlation of sorbitol levels with different clinical outcomes will provide support for the role sorbitol plays in the disease progression of CMT-SORD, and will demonstrate correlation of sorbitol level with clinical outcomes benefit.
Measured: Baseline and up to month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2022
- Study start1 Jan 2022
- Primary completion12 Oct 2024
- Study completion1 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Neuropathy Caused by SORD DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double blind study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Applied Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael E Shy, MD, Study chair, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05397665
- Sponsor's protocol ID
- AT-007-1005
- Acronym
- INSPIRE
- Status last verified
- Jun 2026
- First submitted
- 23 May 2022
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05397665
- Acronym / sponsor ID
- INSPIRE / AT-007-1005
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Applied Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 12 Oct 2024 (actual)
- Study completion
- 1 Jun 2026 (actual)
- First posted
- 31 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This international, multi-center, randomized, double-blinded, placebo-controlled, phase 2-3 study is designed to assess the pharmacodynamic (PD) efficacy of AT-007 treatment, as well as the clinical benefit of long term administration to patients with SORD Deficiency utilizing a series of functional, patient-reported, and clinical outcomes measures.Safety and pharmacokinetics (PK) of AT-007 will also be evaluated. The study consists of Biomarker and Efficacy Assessments and an open-label extension (OLE) of active treatment for qualified patients.
Patients (18-55 years old) with SORD deficiency will be stratified according to their 10MWRT score (a single component of the CMT-FOM) and sex (male vs female). They will then be randomized in a 2:1 ratio to AT-007 20 mg/kg once daily (QD) or placebo.
The study will be conducted at up to 13 sites worldwide. A total of up to 72 subjects will be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double blind study
| Arm | Type | Receives |
|---|---|---|
| AT-007 | Active comparator | Drug: AT-007AT-007 is an Aldose reductase inhibitor |
| Placebo | Sham comparator | Drug: PlaceboIs an non-active control |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (30 listed)
- 10MWRT 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AT-007Also: GovorestatAT-007, aldose reductase inhibitor | Drug | AT-007 |
| PlaceboAlso: Liquid oral vehicle suspensionLiquid oral suspension | Drug | Placebo |
Primary outcome
10-meter walk-run test (10MWRT).
Time frame: baseline and up to month 24
The 10MWRT is a timed functional test used to measure walking or running speed over 10 meters by the study population
Blood sorbitol levels
Time frame: Baseline and up to 3 months.
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.
5 secondary outcomes
Charcot Marie Tooth Functional Outcome Measure (CMT-FOM)
Time frame: Baseline and up to month 24
Charcot Marie Tooth Health Index (CMTHI)
Time frame: Baseline and up to month 24
Exit Interview
Time frame: To be completed at month 24
Muscle Magnetic Resonance Imaging (MRI)
Time frame: Baseline and up to month 24 month
Blood Sorbitol Levels and Correlation with Clinical Outcomes
Time frame: Baseline and up to month 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael E Shy, MD study chair
University of Iowa
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing AT-007 in people with Hereditary Neuropathy Caused by SORD Deficiency, run by Applied Therapeutics, Inc. at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Czechia, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
10-meter walk-run test (10MWRT). (time frame: baseline and up to month 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2026.