Pmm2-CDG Clinical Trial
Official title:
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)
Verified date | May 2024 |
Source | Maggie's Pearl, LLC |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 40 |
Est. completion date | December 31, 2025 |
Est. primary completion date | February 28, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 2 Years to 17 Years |
Eligibility | 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: 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. |
Country | Name | City | State |
---|---|---|---|
United States | Mayo Clinic | Rochester | Minnesota |
Lead Sponsor | Collaborator |
---|---|
Maggie's Pearl, LLC |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in sorbitol (mmol/mol creatinine) | Change in sorbitol from baseline between study arms | 9 months | |
Primary | Change in ICARS | Change in ICARS from baseline between study arms | 9 months | |
Primary | Change in Antithrombin III (ATIII) | Change in ATIII from baseline between study arms | 9 months | |
Secondary | Change of Body Max Index (BMI) percentile | Change of BMI percentile from baseline between study arms | 9 months | |
Secondary | Change of factor XI activity percentage | Change of factor XI activity from baseline between study arms | 9 months | |
Secondary | Change of liver transaminases (U/L) | Change of liver transaminases from baseline between study arms | 9 months | |
Secondary | Change of transferrin glycosylation (ratio) | Change of transferrin glycosylationfrom baseline between study arms | 9 months | |
Secondary | Change in Nijmegen Pediatric CDG Rating Scale (NPCRS) score | Change in NPCRS from baseline between study arms | 9 months | |
Secondary | Change of normalized mannitol (mmol/mol creatinine) | Change of normalized mannitol from baseline between study arms | 9 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05549219 -
24-Week Study to Assess the PD, Safety, Tolerability, and PK of GLM101 in Participants With PMM2-CDG
|
Phase 2 | |
Terminated |
NCT04679389 -
Acetazolamide Efficacy in Ataxia in PMM2-CDG
|
Phase 2/Phase 3 |