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TerminatedNCT04925960Updated Sep 25, 2025

Oral Epalrestat Therapy in Pediatric Subjects With PMM2-CDG

A Phase 3 interventional study of Epalrestat and Placebo in Pmm2-CDG, Phosphomannomutase 2 Deficiency and Phosphomannomutase 2 Congenital Disorder of Glycosylation, sponsored by Maggie's Pearl, LLC. Terminated at 1 site in United States. Open to participants aged 2 Years to 17 Years. Per ClinicalTrials.gov, last updated 2025-09-25.

Sponsored by Maggie's Pearl, LLC · Phase 3, Interventional, and Treatment

Why this study was terminated
Due to futility

From the registry’s dates

  • Primary completion was Feb 2025, 1 year 7 months ago, and no results have been posted to the registry.
Phase
Phase 3
Study type
Interventional
Enrollment
42
Allocation
Randomized
Ages
2 Years to 17 Years
Sex
All
01

Study summary

This is a prospective, single-center, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and clinical and metabolic improvement of pediatric subjects with PMM2-CDG on oral epalrestat therapy vs. placebo.

Read the detailed description

This is a prospective, single-center, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and clinical and metabolic improvement of pediatric subjects with PMM2-CDG on oral epalrestat therapy vs. placebo. The primary study objective is to evaluate the safety and probable benefit of oral epalrestat therapy in pediatric subjects with PMM2-CDG. Study outcomes include evaluating the metabolic improvement of pediatric subjects treated with oral epalrestat therapy compared to placebo, evaluating safety, clinical improvement, and pharmocokinetics (PK) of oral epalrestat therapy in pediatric subjects compared to placebo, and evaluating urine polyols, adverse events, laboratory data, other safety measures, PK, and Quality of Life surveys to measure clinical improvement.

02

Conditions studied

  • Pmm2-CDG
  • Phosphomannomutase 2 Deficiency
  • Phosphomannomutase 2 Congenital Disorder of Glycosylation
  • Phosphomannomutase II Congenital Disorder of Glycosylation
  • Phosphomannomutase II Deficiency
03

In context

Lead sponsor

This is the only study on the registry with Maggie's Pearl, LLC as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
2 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age ≥ 2 and \< 18 years
  2. Diagnosis of PMM2-CDG, based on molecularly confirmed biallelic PMM2 pathogenic variants (can be historical diagnosis with lab report on file)
  3. Informed consent (and assent, as applicable) document personally signed by the legally authorized representative of the patient, indicating that the patient's parent/guardian has been informed and agreed to all aspects of the study
  4. Be willing and able to adhere to the study assessments and schedule described in the protocol and consent/assent documents
  5. Negative urine pregnancy test (only for female subjects of child-bearing potential)
  6. 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.

Exclusion criteria

Exclusion Criteria:

  1. Known or suspected other known CDG
  2. Known allergy to aldose reductase inhibitors
  3. Hypersensitivity to epalrestat

  4. Hepatic impairment defined as any one of the following:

    1. AST/ALT >5x ULN in the 6 months prior to screening
    2. Bilirubin >2X ULN in the last 6 months prior to screening
    3. Synthetic liver dysfunction (albumin deficiency \< 2.8 mmol/L) at screening, or
    4. Diagnosis of liver fibrosis (Fibroscan > 7 kPa) confirmed by liver elastogram at screening
  5. Renal impairment defined as serum creatinine: > 0.5 mg/dL (≤ 6 years); > 0.7 mg/dL (7-10 years); > 1.24 mg/dL (≥ 11 years)
  6. Low platelet count (\< 125x109 /L)
  7. Any other clinically significant lab abnormality which, in the opinion of the investigator, should be exclusionary
  8. Anemia (Hgb \< 10 g/dL)
  9. Use of an investigational drug, including acetazolamide, in the past 28 days; use of an investigational biologic in the past 12 months
  10. Concurrent or planned participation in interventional protocol or use of any other unapproved therapeutics, and,
  11. 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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
42 participants (actual)

Study arms

  • Experimental
    Epalrestat

    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.

    Drug: Epalrestat

  • Placebo comparator
    Placebo

    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.

    Drug: Placebo

Interventions

  • DrugEpalrestat

    Epalrestat is a noncompetitive and reversible aldose reductase inhibitor (ARI) used for the treatment of diabetic neuropathy in Japan. The drug's ability to safely improve symptoms of neuropathy alone by reducing oxidative stress, increasing glutathione levels, and reducing intracellular sorbitol accumulation make it a desirable medication for PMM2-CDG patients who commonly suffer with various neuropathies. However, work recently conducted by Perlara, a public benefit company with the mandate to screen existing commercially available drugs for possible application in rare diseases, has demonstrated that Epalrestat can also elevate the level PMM2 produced endogenously. This may reduce the severity of the morbidities associated with PMM2-CDG.

  • DrugPlacebo

    The placebo capsule with be identical in appearance to the Epalrestat capsule. It will contain microcrystalline cellulose filler in a gelatin capsule.

06

What researchers measure

Primary outcomes

  1. Change in sorbitol (mmol/mol creatinine)

    Change in sorbitol from baseline between study arms

    Time frame: 9 months

  2. Change in ICARS

    Change in ICARS from baseline between study arms

    Time frame: 9 months

  3. Change in Antithrombin III (ATIII)

    Change in ATIII from baseline between study arms

    Time frame: 9 months

Secondary outcomes

  1. Change of Body Max Index (BMI) percentile

    Change of BMI percentile from baseline between study arms

    Time frame: 9 months

  2. Change of factor XI activity percentage

    Change of factor XI activity from baseline between study arms

    Time frame: 9 months

  3. Change of liver transaminases (U/L)

    Change of liver transaminases from baseline between study arms

    Time frame: 9 months

  4. Change of transferrin glycosylation (ratio)

    Change of transferrin glycosylationfrom baseline between study arms

    Time frame: 9 months

  5. Change in Nijmegen Pediatric CDG Rating Scale (NPCRS) score

    Change in NPCRS from baseline between study arms

    Time frame: 9 months

  6. Change of normalized mannitol (mmol/mol creatinine)

    Change of normalized mannitol from baseline between study arms

    Time frame: 9 months

07

Study locations

1 site
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 25, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04925960
Lead sponsor
Maggie's Pearl, LLC
Responsible party
Sponsor
First posted
Jun 14, 2021
Start date
Nov 10, 2022
Primary completion
Feb 28, 2025
Completion
Feb 28, 2025
Last update
Sep 25, 2025

Study contacts

Eva Morava-Kozicz, MD, PhD
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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