Epalrestat for PMM2-CDG

Overseen By Jess Ward, BS

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Eva Morava-Kozicz

Must not be taking: Aldose reductase inhibitors

Disqualifiers: Other CDG, Hepatic impairment, Renal impairment, Anemia, 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: 9 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called epalrestat, taken by mouth, to see if it helps children with a rare genetic disorder called PMM2-CDG. The goal is to check if the medication is safe and if it improves their metabolism and overall health. Researchers will compare the results to ensure the findings are accurate.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have used an investigational drug in the past 28 days or plan to use unapproved therapeutics during the trial.

How does the drug Epalrestat differ from other treatments for PMM2-CDG?

Epalrestat is unique for PMM2-CDG as there are no standard treatments for this condition, making it a novel option. It works by inhibiting aldose reductase, an enzyme involved in sugar metabolism, which is different from other treatments that might not target this specific pathway. ^{1 2 3 4 5}

Research Team

Eva Morava-Kozicz, MD, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for children aged 2 to under 18 with PMM2-CDG, a rare genetic disorder. They must be able to follow the study plan and not be pregnant or at risk of pregnancy without proper contraception. Kids can't join if they're allergic to epalrestat, have anemia, kidney problems, low platelets, liver issues, other CDGs or are on certain other drugs.

Inclusion Criteria

For subjects of child-bearing potential-only, subject has been counseled on and agrees to the requirement either for double barrier contraceptive methods and/or for total abstinence from prior to randomization through 3-months after the cessation of treatment.

Be willing and able to adhere to the study assessments and schedule described in the protocol and consent/assent documents

I am between 2 and 17 years old.

Exclusion Criteria

I have had liver problems, like high enzyme levels or liver stiffness, in the last 6 months.

Any other medical condition, which, in the opinion of the investigator, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results.

I haven't used any experimental drugs or biologics recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral epalrestat or placebo, administered 3 times per day, to assess safety, tolerability, and clinical and metabolic improvement

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Epalrestat
• Placebo

Trial Overview The study tests oral Epalrestat against a placebo in kids with PMM2-CDG. It's designed to see if it's safe and tolerable and whether it improves their condition. Participants will randomly receive either the drug or placebo without knowing which one they get.

Participant Groups

Group I: Epalrestat Experimental Treatment 1 Intervention

Epalrestat will be administered orally, 3 times per day (TID) spaced out as evenly as possible over 24 hours in a divided dose starting on Day 1 of the Study.

Group II: Placebo Placebo Group 1 Intervention

Placebo will be administered orally, 3 times per day (TID) spaced out as evenly as possible over 24 hours in a divided dose starting on Day 1 of the Study.

Who Is Running the Clinical Trial?

Eva Morava-Kozicz

Lead Sponsor

Trials

4

Recruited

80+

Maggie's Pearl, LLC

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

In a study involving human prostate cancer models, the combination of estramustine and docetaxel significantly prolonged tumor growth delay (TGD) in docetaxel-resistant tumors, achieving a TGD of 50 days compared to 18 days with estramustine alone.

Despite the efficacy of the combination treatment, its use may be limited in elderly patients or those with comorbidities due to the risk of serious side effects, such as venous thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preclinical therapeutic schedule optimizing docetaxel plus estramustine administration in prostate cancer. Dahmani, A., de Plater, L., Guyader, C., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacodynamics, safety, and immunogenicity of Pelmeg&#174;, a pegfilgrastim biosimilar in healthy subjects. [2023]

2. England pubmed.ncbi.nlm.nih.gov

A preclinical therapeutic schedule optimizing docetaxel plus estramustine administration in prostate cancer. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of Pelmeg&#174;, a pegfilgrastim biosimilar in healthy subjects. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a proposed pegfilgrastim biosimilar MSB11455 versus the reference pegfilgrastim Neulasta&#174; in healthy subjects: A randomized, double-blind trial. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Pegfilgrastim supports delivery of FEC-100 chemotherapy in elderly patients with high risk breast cancer: a randomized phase 2 trial. [2018]