A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Study of Oral Epalrestat Therapy in Pediatric Subjects With Phosphomannomutase 2-congenital Disorder of Glycosylation (PMM2-CDG)
Overview
- Phase
- Phase 3
- Intervention
- Epalrestat
- Conditions
- Pmm2-CDG
- Sponsor
- Maggie's Pearl, LLC
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Change in Antithrombin III (ATIII)
- Status
- Terminated
- Last Updated
- 7 months ago
Overview
Brief 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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 2 and \< 18 years
- •Diagnosis of PMM2-CDG, based on molecularly confirmed biallelic PMM2 pathogenic variants (can be historical diagnosis with lab report on file)
- •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
- •Be willing and able to adhere to the study assessments and schedule described in the protocol and consent/assent documents
- •Negative urine pregnancy test (only for female subjects of child-bearing potential)
- •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
- •Known or suspected other known CDG
- •Known allergy to aldose reductase inhibitors
- •Hypersensitivity to epalrestat
- •Hepatic impairment defined as any one of the following:
- •AST/ALT \>5x ULN in the 6 months prior to screening
- •Bilirubin \>2X ULN in the last 6 months prior to screening
- •Synthetic liver dysfunction (albumin deficiency \< 2.8 mmol/L) at screening, or
- •Diagnosis of liver fibrosis (Fibroscan \> 7 kPa) confirmed by liver elastogram at screening
- •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)
- •Low platelet count (\< 125x109 /L)
Arms & Interventions
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.
Intervention: Epalrestat
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Change in Antithrombin III (ATIII)
Time Frame: 9 months
Change in ATIII from baseline between study arms
Change in sorbitol (mmol/mol creatinine)
Time Frame: 9 months
Change in sorbitol from baseline between study arms
Change in ICARS
Time Frame: 9 months
Change in ICARS from baseline between study arms
Secondary Outcomes
- Change of Body Max Index (BMI) percentile(9 months)
- Change of factor XI activity percentage(9 months)
- Change of normalized mannitol (mmol/mol creatinine)(9 months)
- Change in Nijmegen Pediatric CDG Rating Scale (NPCRS) score(9 months)
- Change of liver transaminases (U/L)(9 months)
- Change of transferrin glycosylation (ratio)(9 months)