Oral Epalrestat Therapy in Pediatric Subjects With PMM2-CDG
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|ClinicalTrials.gov Identifier: NCT04925960|
Recruitment Status : Not yet recruiting
First Posted : June 14, 2021
Last Update Posted : April 5, 2022
|Condition or disease||Intervention/treatment||Phase|
|Pmm2-CDG Phosphomannomutase 2 Deficiency Phosphomannomutase 2 Congenital Disorder of Glycosylation Phosphomannomutase II Congenital Disorder of Glycosylation Phosphomannomutase II Deficiency||Drug: Epalrestat Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Subjects will be randomized to treatment or placebo. Patients and study staff will be blinded to the study arm.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Patients and all study personnel will remain blinded to the original treatment assignment until study close.|
|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)|
|Estimated Study Start Date :||July 1, 2022|
|Estimated Primary Completion Date :||February 28, 2026|
|Estimated Study Completion Date :||December 31, 2026|
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.
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.
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.
The placebo capsule with be identical in appearance to the Epalrestat capsule. It will contain lactose monohydrate filler in a gelatin capsule.
- 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
- Change in Antithrombin III (ATIII) [ Time Frame: 9 months ]Change in ATIII from baseline between study arms
- Change of Body Max Index (BMI) percentile [ Time Frame: 9 months ]Change of BMI percentile from baseline between study arms
- Change of factor XI activity percentage [ Time Frame: 9 months ]Change of factor XI activity from baseline between study arms
- Change of liver transaminases (U/L) [ Time Frame: 9 months ]Change of liver transaminases from baseline between study arms
- Change of transferrin glycosylation (ratio) [ Time Frame: 9 months ]Change of transferrin glycosylationfrom baseline between study arms
- Change in Nijmegen Pediatric CDG Rating Scale (NPCRS) score [ Time Frame: 9 months ]Change in NPCRS from baseline between study arms
- Change of normalized mannitol (mmol/mol creatinine) [ Time Frame: 9 months ]Change of normalized mannitol from baseline between study arms
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04925960
|Contact: Eva Morava-Kozicz, MD, PhDemail@example.com|
|Contact: Kaitlin Schwartz, BSfirstname.lastname@example.org|
|Principal Investigator:||Eva Morava-Kozicz, MD, PhD||Mayo Clinic|