AT-007 for Sensory and Autonomic Neuropathy

(INSPIRE Trial)

Not currently recruiting at 10 trial locations

Overseen By Michael E Shy, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Applied Therapeutics, Inc.

Must not be taking: Prescription medications

Disqualifiers: Diabetes, Neuropathy, Myopathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment called AT-007 for individuals with SORD Deficiency, a condition affecting nerves responsible for sensation and autonomic functions like sweating. The study compares AT-007 to a placebo (a non-active substance) to determine if it can safely improve symptoms over two years. Candidates for this trial include those with a confirmed diagnosis of SORD Deficiency and stable medication routines. As a Phase 2, Phase 3 trial, this research evaluates the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it excludes those using prescription medications likely to interfere with the study drug. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that AT-007 is likely to be safe for humans?

Research has shown that AT-007 has been tested in other conditions, such as Classic Galactosemia, with strong safety results over three years in 185 patients. Most patients tolerated the treatment well. In studies for Sorbitol Dehydrogenase Deficiency, AT-007 was tested for 24 months and demonstrated promising safety outcomes. This treatment is an aldose reductase inhibitor, which helps prevent certain sugars from accumulating in the body. Overall, evidence suggests that AT-007 is well-tolerated, with no major safety concerns reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for sensory and autonomic neuropathy focus on managing symptoms with medications like antidepressants, anticonvulsants, or pain relievers. But AT-007 works differently by targeting the root cause of the condition. It's an aldose reductase inhibitor, which means it aims to prevent nerve damage by stopping the buildup of harmful sugar alcohols in nerve cells. Researchers are excited because this new approach could potentially slow down or even halt disease progression, offering hope for more long-term relief compared to traditional symptom management.

What evidence suggests that AT-007 might be an effective treatment for SORD Deficiency?

Research has shown that AT-007, a medication under study in this trial, offers promising results for conditions like Classic Galactosemia, which resembles SORD Deficiency. Specifically, studies involving 185 patients over three years demonstrated the medication's effectiveness and safety. Patients experienced slower disease progression and improved health outcomes, with harmful substances like sorbitol reduced for up to 24 months. These findings suggest that AT-007 could also effectively treat SORD Deficiency by targeting similar pathways and reducing toxic buildup. ^{1 3 6 7 8}

Who Is on the Research Team?

Michael E Shy, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with SORD Deficiency, confirmed by medical records and gene analysis. Participants must have elevated sorbitol levels and agree to use birth control if they can bear children. Excluded are those with very severe disease, significant other health issues, high or low BMI outside set limits, substance abuse history, recent blood donations or participation in another drug study.

Inclusion Criteria

I cannot have children or agree to use birth control during the study.

I am a male who is either surgically sterile or will use birth control during and after the study.

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

Exclusion Criteria

I do not have any major health issues that could affect the study's safety or results.

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

History of significant drug allergy or drug hypersensitivity

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either AT-007 or placebo daily for 24 months

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AT-007
• Placebo

Trial Overview

The trial tests the efficacy and safety of AT-007 against a placebo over 24 months in patients with SORD Deficiency. It's randomized and double-blind, meaning neither the researchers nor participants know who receives the actual drug versus the placebo.

How Is the Trial Designed?

Group I: AT-007 Active Control 1 Intervention

AT-007 is an Aldose reductase inhibitor

Group II: Placebo Placebo Group 1 Intervention

Is an non-active control

Who Is Running the Clinical Trial?

Applied Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

900+

Citations

1.

appliedtherapeutics.com

appliedtherapeutics.com/pipeline/govorestat/

AT-007 Aldose Reductase, Galactosemia

Additional supportive studies resulted in robust efficacy and safety data across 185 patients with Classic Galactosemia over 3 years. The results of the ...

2.

ir.appliedtherapeutics.com

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

Press Release Details

Slowing of progression of disease observed via MRI at 24 months. Improvements in outcomes and reduction in sorbitol maintained through 24 ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/7579007/

Effects of an aldose reductase inhibitor, epalrestat, on ...

Effects of an aldose reductase inhibitor, epalrestat, on diabetic neuropathy. Clinical benefit and indication for the drug assessed from the results of a ...

4.

appliedtherapeutics.gcs-web.com

appliedtherapeutics.gcs-web.com/news-releases/news-release-details/applied-therapeutics-announces-positive-results-12-month-interim

Press Release Details

Applied Therapeutics Announces Positive Results from 12-month Interim Analysis of Govorestat (AT-007) in the Ongoing INSPIRE Phase 3 Trial in ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05397665

Study Details | NCT05397665 | Pharmacodynamic EffIcacy ...

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 ...

6.

appliedtherapeutics.gcs-web.com

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

Applied Therapeutics Presents Full 12-Month Clinical Results ...

Full 12-month clinical results and new topline data from 18 and 24 months from the INSPIRE Phase 2/3 trial of govorestat (AT-007) for the treatment of Sorbitol ...

7.

ir.appliedtherapeutics.com

ir.appliedtherapeutics.com/news-releases/news-release-details/applied-therapeutics-present-data-007-govorestat-treatment-sord

Press Release Details

A randomized study to evaluate pharmacodynamic and clinical benefit of AT-007 in patients with sorbitol dehydrogenase deficiency.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6400176/

Aldose reductase inhibitor ranirestat significantly improves ...

Ranirestat (40 mg/day) was well tolerated and improved nerve conduction velocity. Regarding symptoms and signs, no detectable benefits over the placebo were ...