Pmm2-CDGPhase 3NCT04925960
Oral Epalrestat Therapy in Pediatric Subjects With PMM2-CDG
A Phase 3 study testing Epalrestat in people with Pmm2-CDG and Phosphomannomutase 2 Deficiency, run by Maggie's Pearl, LLC at 1 site in United States.
Trial 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 more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Pmm2-CDG, Phosphomannomutase 2 Deficiency, Phosphomannomutase 2 Congenital Disorder of Glycosylation
- What is being tested?
- Epalrestat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Nov 2022to 28 Feb 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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)
- Any other clinically significant lab abnormality which, in the opinion of the investigator, should be exclusionary
- Anemia (Hgb < 10 g/dL)
- Use of an investigational drug, including acetazolamide, in the past 28 days; use of an investigational biologic in the past 12 months
- Concurrent or planned participation in interventional protocol or use of any other unapproved therapeutics, and,
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
- Conditions
- Pmm2-CDG, Phosphomannomutase 2 Deficiency, Phosphomannomutase 2 Congenital Disorder of Glycosylation, Phosphomannomutase II Congenital Disorder of Glycosylation, Phosphomannomutase II Deficiency
- Being tested
- Epalrestat, Placebo
- Medical subject headings
- Congenital disorder of glycosylation type 1A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpalrestatDrug
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.
PlaceboDrug
The placebo capsule with be identical in appearance to the Epalrestat capsule. It will contain microcrystalline cellulose filler in a gelatin capsule.
| Study group | Role | What they receive |
|---|---|---|
| Epalrestat | Experimental | 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. Receives: Drug: Epalrestat |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in sorbitol (mmol/mol creatinine)
Change in sorbitol from baseline between study arms
Measured: 9 months
Change in ICARS
Change in ICARS from baseline between study arms
Measured: 9 months
Change in Antithrombin III (ATIII)
Change in ATIII from baseline between study arms
Measured: 9 months
Secondary outcomes (6)
Change of Body Max Index (BMI) percentile
Change of BMI percentile from baseline between study arms
Measured: 9 months
Change of factor XI activity percentage
Change of factor XI activity from baseline between study arms
Measured: 9 months
Change of liver transaminases (U/L)
Change of liver transaminases from baseline between study arms
Measured: 9 months
Change of transferrin glycosylation (ratio)
Change of transferrin glycosylationfrom baseline between study arms
Measured: 9 months
Change in Nijmegen Pediatric CDG Rating Scale (NPCRS) score
Change in NPCRS from baseline between study arms
Measured: 9 months
Change of normalized mannitol (mmol/mol creatinine)
Change of normalized mannitol from baseline between study arms
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2021
- Study start10 Nov 2022
- Primary completion28 Feb 2025
- Study completion28 Feb 2025
Why it stopped: Due to futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pmm2-CDGStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized to treatment or placebo. Patients and study staff will be blinded to the study arm.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maggie's Pearl, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eva Morava-Kozicz, MD, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04925960
- Sponsor's protocol ID
- 21-000492
- Status last verified
- Sep 2025
- First submitted
- 8 Jun 2021
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04925960
- Acronym / sponsor ID
- 21-000492
- Conditions
- Pmm2-CDG, Phosphomannomutase 2 Deficiency, Phosphomannomutase 2 Congenital Disorder of Glycosylation, Phosphomannomutase II Congenital Disorder of Glycosylation, Phosphomannomutase II Deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to futility
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Maggie's Pearl, LLCIndustry (pharma, biotech, devices)
- Study start
- 10 Nov 2022 (actual)
- Primary completion
- 28 Feb 2025 (actual)
- Study completion
- 28 Feb 2025 (actual)
- First posted
- 14 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized to treatment or placebo. Patients and study staff will be blinded to the study arm.
| Arm | Type | Receives |
|---|---|---|
| Epalrestat | Experimental | Drug: EpalrestatEpalrestat 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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 may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (15 listed)
- Known or suspected other known CDG
- Known allergy to aldose reductase inhibitors
- Hypersensitivity to epalrestat
- Hepatic impairment defined as any one of the following:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EpalrestatEpalrestat 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. | Drug | Epalrestat |
| PlaceboThe placebo capsule with be identical in appearance to the Epalrestat capsule. It will contain microcrystalline cellulose filler in a gelatin capsule. | Drug | Placebo |
Primary outcome
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
6 secondary outcomes
Change of Body Max Index (BMI) percentile
Time frame: 9 months
Change of factor XI activity percentage
Time frame: 9 months
Change of liver transaminases (U/L)
Time frame: 9 months
Change of transferrin glycosylation (ratio)
Time frame: 9 months
Change in Nijmegen Pediatric CDG Rating Scale (NPCRS) score
Time frame: 9 months
Change of normalized mannitol (mmol/mol creatinine)
Time frame: 9 months
Results and safety
The study was stopped early (reason given: Due to futility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Pmm2-CDG
Enrolling by invitationPhase 2
Open-Label Extension Study to Assess GLM101 in PMM2-CDG Patients
Pmm2-CDG, Phosphomannomutase 2 Deficiency
Active, not recruitingPhase 2/3
A Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 in Participants With PMM2-CDG
Phosphomannomutase 2 Deficiency, PMM2-CDG
RecruitingObservational study
Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
Congenital Disorders of Glycosylation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva Morava-Kozicz, MD, PhD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Epalrestat in people with Pmm2-CDG and Phosphomannomutase 2 Deficiency, run by Maggie's Pearl, LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to futility). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in sorbitol (mmol/mol creatinine) (time frame: 9 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025.