Govorestat for Charcot-Marie-Tooth Disease

Not yet recruiting at 12 trial locations

Overseen By Evan Bailey, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Applied Therapeutics, Inc.

Must not be taking: Antidepressants, Antipsychotics, others

Disqualifiers: Diabetes, Hypertension, HIV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term effects of a drug called govorestat for individuals with a specific nerve disease known as CMT-SORD. Participants will receive either govorestat or a placebo (a non-active pill) to determine if the drug helps manage symptoms over up to 36 months. This study suits individuals diagnosed with CMT-SORD who have high blood sorbitol levels and are stable on their current medications. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Do I have to stop taking my current medications for the trial?

You can continue taking your current medications, but they must be stable for at least 1 month before the trial and throughout the study. All medications, including over-the-counter ones, need to be reviewed and approved by the study doctor.

Is there any evidence suggesting that govorestat is likely to be safe for humans?

Research has shown that govorestat is well tolerated for up to 24 months. In earlier studies, patients using govorestat did not experience major safety problems. This treatment has proven safe, with no reports of serious side effects from patients. Govorestat reduces sorbitol levels, which can help protect nerves, an important factor in treating Charcot-Marie-Tooth disease. Overall, current findings suggest that govorestat is safe to use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Govorestat for treating Charcot-Marie-Tooth disease because it introduces a new approach by inhibiting aldose reductase. Unlike current treatments that mainly manage symptoms, Govorestat targets the underlying biochemical pathway thought to contribute to nerve damage in this condition. This mechanism has the potential to slow disease progression, offering hope for more effective management of Charcot-Marie-Tooth disease than existing options.

What evidence suggests that govorestat might be an effective treatment for Charcot-Marie-Tooth disease?

Research has shown that Govorestat, also known as AT-007, may help treat Charcot-Marie-Tooth Disease type SORD (CMT-SORD). In earlier studies, Govorestat led to noticeable improvements in a key health measure related to CMT after 12 months, with patients continuing to experience health benefits over 18 and 24 months. In this trial, participants will receive either Govorestat or a placebo. Govorestat lowers sorbitol levels in the blood. High sorbitol levels are believed to cause nerve damage in CMT-SORD, so reducing them might help protect nerves and improve their function. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with Charcot-Marie-Tooth Disease linked to SORD deficiency. Specific eligibility details are not provided, but typically participants must meet certain health criteria and not have conditions that could interfere with the study or pose additional risks.

Inclusion Criteria

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

I have been diagnosed with CMT2 or dHMN, have high blood sorbitol, and a SORD gene mutation.

I am a man or a woman not pregnant or breastfeeding, aged 16 to 65.

Exclusion Criteria

Body Mass Index (BMI) >35 kg/m2

I cannot walk by myself.

Hemoglobin (Hgb) < 10.0 g/dL at Screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive govorestat or placebo for up to 36 months to assess long-term efficacy and clinical benefit

36 months

Interim Analysis

A pre-planned interim analysis will be conducted at 24 months to determine if clinical benefit is met

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Govorestat

Trial Overview The trial is testing Govorestat's long-term effectiveness in treating CMT-SORD over a period of up to 36 months. Patients will be randomly assigned to receive either Govorestat or a placebo without knowing which one they're getting (double-blind).

How Is the Trial Designed?

Group I: Govorestat Active Control 1 Intervention

Govorestat is an aldose reductase inhibitor

Group II: Placebo Placebo Group 1 Intervention

Non-active control

Who Is Running the Clinical Trial?

Applied Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

900+

Citations

1. ir.appliedtherapeutics.com ir.appliedtherapeutics.com/news-releases/news-release-details/applied-therapeutics-presents-full-12-month-clinical-results-and

Press Release Details Govorestat treatment demonstrated a statistically significant improvement (p=0.039) on key secondary endpoint, CMT-HI at 12 months. A ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07191912

Confirmatory Study of Govorestat in CMT-SORD This study is designed to assess the long-term efficacy and clinical benefit of AT-007 in patients with CMT-SORD.

3. cmtrf.org cmtrf.org/applied-therapeutics-presents-findings-from-phase-2-3-clinical-trial-of-govorestat-in-cmt-sord/

Applied Therapeutics Presents Findings From Phase 2/3 ... Highlights from the 18- and 24-month results include sustained reductions in blood sorbitol levels and sustained improvements in the CMT-Health ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/14737175.2025.2470980

Charcot-Marie-Tooth disease: a review of clinical ... The INSPIRE trial is based on the hypothesis that using an aldose reductase inhibitor (AT-007/Govorestat) to reduce sorbitol levels will halt the ...

5. appliedtherapeutics.com appliedtherapeutics.com/pipeline/govorestat/

AT-007 Aldose Reductase, Galactosemia Govorestat has demonstrated rapid and sustained reductions in galactitol in clinical trials, which resulted in a meaningful benefit on clinical outcomes across ...

6. cmtausa.org cmtausa.org/simply-cmt/cmt-sord-pns2025/

Applied Therapeutics Shares 24-Month Trial Results at PNS The company reported that govorestat remained safe and well tolerated through 24 months and that a potential FDA new drug application (NDA) ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07191912

Confirmatory Study of Govorestat in CMT-SORD This study is designed to assess the long-term efficacy and clinical benefit of AT-007 in patients with CMT-SORD.

8. hnf-cure.org hnf-cure.org/triad/triad-therapeutics/applied-therapeutics/hnf-partner-cmt-sord-clinical-trial-update/

HNF Partner: CMT-SORD Clinical Trial Update Govorestat is an orphan drug designed to lower sorbitol levels and protect nerves. The INSPIRE trial tested its effect on symptoms, walking ...