Charcot-Marie-Tooth Disease With Sorbitol Dehydrogenase Deficiency (CMT-SORD)Phase 3NCT07191912
Confirmatory Study of Govorestat in CMT-SORD
A Phase 3 study testing Govorestat in people with Charcot-Marie-Tooth Disease With Sorbitol Dehydrogenase Deficiency (CMT-SORD), run by Applied Therapeutics, Inc. at 13 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Charcot-Marie-Tooth Disease With Sorbitol Dehydrogenase Deficiency (CMT-SORD)
- What is being tested?
- Govorestat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 13 sitesin 7 countries
- Study dates
- May 2026to Jan 2029
- Phase
- Phase 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 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older 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 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.
Who cannot join
- 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.
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- 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).
- 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 Investigator 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 Investigator 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, medical history 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
13 sites in 7 countries.
13 sites in 7 countries
Germany3 sites
Uniklinik of the RWTH Aachen University
Aachen, 52074
Charité - Universitätsmedizin Berlin
Berlin, 10117
University Medicine Gottingen (UMG)
Göttingen, 37075
United States2 sites
Clinic for Special Children
Gordonville, Pennsylvania, 17529
University of Iowa
Iowa City, Iowa, 52242
Spain2 sites
Vall d'Hebron Institut de Recerca (VHIR)
Barcelona, 08035
La Fe University and Polytechnic Hospital
Valencia, 46026
Turkey (Türkiye)2 sites
Koç University Hospital
Istanbul, 34010
Istanbul University
Istanbul, 34093
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Long-Term Clinical Benefit of Govorestat in Patients With Charcot-Marie-Tooth-Sorbitol Dehydrogenase Deficiency (CMT-SORD)
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.
Read the detailed description
This international, multi-center, randomized, double-blinded, placebo-controlled, phase 3 study is designed to assess the efficacy and clinical benefit of long-term govorestat administration to patients with CMT-SORD utilizing functional, patient-reported, and clinical outcomes measures including the CMT-HI, 10MWRT, dorsiflexion, the CMT-FOM, and CMT-related lower extremity muscle MRI parameters along with the long-term effect of govorestat on whole blood sorbitol. Long-term safety of govorestat will also be evaluated.
Patients (16 to 65 years old) with CMT-SORD will be stratified according to their sex (male vs female) and age before randomization in a 2:1 ratio to govorestat 20 mg/kg once daily (QD) or placebo.
There will be a pre-planned Interim Analysis at 2 years (Month 24). If clinical benefit is determined to be met with the Interim Analysis, the study will end and not continue to 3 years.
The study will be conducted at up to 16 sites worldwide. Approximately 155 subjects will be enrolled.
- Being tested
- Govorestat, Placebo Control
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GovorestatDrug
Also called AT-007
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)
Placebo ControlDrug
Placebo will also be provided as a matching liquid suspension to be taken orally QD
| Study group | Role | What they receive |
|---|---|---|
| Govorestat | Active comparator | Govorestat is an aldose reductase inhibitor Receives: Drug: Govorestat |
| Placebo | Placebo comparator | Non-active control Receives: Drug: Placebo Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrollment to the end of treatment at 36 months
Secondary outcomes (7)
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: From enrollment to the end of treatment at 36 months
Dorsiflexion
Maximum isometric dorsiflexion force measured in Newtons using a calibrated dynamometer in a standardized position; higher values indicate greater dorsiflexion strength.
Measured: From enrollment to the end of treatment at 36 months
Charcot-Marie-Tooth, Health Index (CMT-HI) Sub-Domain Scores
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. The CMT-HI has 18 sub-domains, each of which will be evaluated separately.
Measured: From enrollment to the end of treatment at 36 months
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. There are 5 domains (strength, upper limb function, lower limb function, balance, and motility) that are assessed by 13 test items specifically selected to ensure functional/patient-relevance, reliability/validity, and responsiveness to change. Total and sub-domain scores of the CMT-FOM, will be evaluated to detect change over time.
Measured: From enrollment to the end of treatment at 36 months
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: From enrollment to the end of treatment at 36 months
Whole blood sorbitol levels
Patients with CMT-SORD 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. Prior studies have shown a correlation of sorbitol levels with different clinical outcomes in CMT-SORD. We will evaluate the effect of govorestat on whole blood sorbitol levels over time.
Measured: From enrollment to the end of treatment at 36 months
Plasma drug concentration
Plasma drug concentration samples will be obtained pre-dose (within 60 minutes) and at 2, 4, 6, 8 hours after the dose.
Measured: From enrollment through Month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2025
- Study startMay 2026 (estimated)
- Primary completionOct 2028 (estimated)
- Study completionJan 2029 (estimated)
Why it stopped: The study was withdrawn prior to enrollment as the sponsor decided not to proceed with study initiation.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Charcot-Marie-Tooth Disease With Sorbitol Dehydrogenase Deficiency (CMT-SORD)Studies 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 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Applied Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07191912
- Sponsor's protocol ID
- AT-007-1020
- Status last verified
- May 2026
- First submitted
- 10 Sep 2025
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Long-Term Clinical Benefit of Govorestat in Patients With Charcot-Marie-Tooth-Sorbitol Dehydrogenase Deficiency (CMT-SORD)
- ClinicalTrials.gov ID
- NCT07191912
- Acronym / sponsor ID
- AT-007-1020
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was withdrawn prior to enrollment as the sponsor decided not to proceed with study initiation.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Applied Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2026 (estimated)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 25 Sep 2025 (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 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.
Detailed description
This international, multi-center, randomized, double-blinded, placebo-controlled, phase 3 study is designed to assess the efficacy and clinical benefit of long-term govorestat administration to patients with CMT-SORD utilizing functional, patient-reported, and clinical outcomes measures including the CMT-HI, 10MWRT, dorsiflexion, the CMT-FOM, and CMT-related lower extremity muscle MRI parameters along with the long-term effect of govorestat on whole blood sorbitol. Long-term safety of govorestat will also be evaluated.
Patients (16 to 65 years old) with CMT-SORD will be stratified according to their sex (male vs female) and age before randomization in a 2:1 ratio to govorestat 20 mg/kg once daily (QD) or placebo.
There will be a pre-planned Interim Analysis at 2 years (Month 24). If clinical benefit is determined to be met with the Interim Analysis, the study will end and not continue to 3 years.
The study will be conducted at up to 16 sites worldwide. Approximately 155 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 |
|---|---|---|
| Govorestat | Active comparator | Drug: GovorestatGovorestat is an aldose reductase inhibitor |
| Placebo | Placebo comparator | Drug: Placebo ControlNon-active control |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 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 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.
Key exclusion criteria (30 listed)
- 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.
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 |
|---|---|---|
| GovorestatAlso: AT-007Govorestat will be provided as a liquid suspension (200mg/mL) for weight-based administration and administered orally at 20 mg/kg QD (every 24 hours) | Drug | Govorestat |
| Placebo ControlPlacebo will also be provided as a matching liquid suspension to be taken orally QD | Drug | Placebo |
Primary outcome
Charcot-Marie-Tooth, Health Index (CMT-HI) Total Score
Time frame: From enrollment to the end of treatment at 36 months
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.
7 secondary outcomes
10-meter walk-run test (10MWRT)
Time frame: From enrollment to the end of treatment at 36 months
Dorsiflexion
Time frame: From enrollment to the end of treatment at 36 months
Charcot-Marie-Tooth, Health Index (CMT-HI) Sub-Domain Scores
Time frame: From enrollment to the end of treatment at 36 months
Charcot Marie Tooth Functional Outcome Measure (CMT-FOM)
Time frame: From enrollment to the end of treatment at 36 months
Muscle Magnetic Resonance Imaging (MRI)
Time frame: From enrollment to the end of treatment at 36 months
Whole blood sorbitol levels
Time frame: From enrollment to the end of treatment at 36 months
Plasma drug concentration
Time frame: From enrollment through Month 3
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
- Individual participant dataSharing planned: No
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.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Govorestat in people with Charcot-Marie-Tooth Disease With Sorbitol Dehydrogenase Deficiency (CMT-SORD), run by Applied Therapeutics, Inc. at 13 sites in 7 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 6 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: withdrawn, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany, United States, France, Spain, Turkey (Türkiye) and 2 more countries. 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 phase mean?
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 was withdrawn before enrolling participants, so there are no results.
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?
Charcot-Marie-Tooth, Health Index (CMT-HI) Total Score (time frame: From enrollment to the end of treatment at 36 months). 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 29 May 2026.