Treatment of Medium Chain Acyl-CoA Dehydrogenase Deficiency with Sodium Phenylbutyrate

A Phase 2, Open-label, Fixed-dose Study to Assess the Efficacy of Sodium Phenylbutyrate (ACER-001) in Treating Pediatric and Adult Patients With Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency Resulting From the Prevalent ACADM c.985 A>G (K304E) Mutation

This study is testing if sodium phenylbutyrate can safely help people aged 4 and older with medium-chain acyl-CoA dehydrogenase deficiency feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 4 Years and up
• Sex: All
• Sponsor: University of Pittsburgh (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT06773026 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of sodium phenylbutyrate (ACER-001) in patients aged 4 years and older diagnosed with medium-chain acyl-CoA dehydrogenase deficiency (MCADD) due to the common ACADM c.985 A>G mutation. Participants will undergo a series of outpatient visits, including screening, continuous glucose monitoring, and blood draws to assess the medication's effects. The study spans approximately 5 weeks, with participants receiving the medication in a controlled setting and monitored for pharmacokinetics. The goal is to determine if this FDA-approved drug can effectively treat MCADD.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 4 years and older with a confirmed diagnosis of MCADD and the specific genetic mutation.

Not a fit: Patients without the common c.985 A>G mutation or those under 4 years of age may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve metabolic control and quality of life for patients with MCADD.

How similar studies have performed: Previous studies have indicated potential effectiveness of sodium phenylbutyrate for similar metabolic disorders, suggesting a promising avenue for MCADD treatment.

Eligibility criteria

Inclusion Criteria:

1. A diagnosis of MCADD and molecular confirmation of at least one copy of the common c.985A\>G mutation.
2. ≥4 years of age
3. Able to perform and comply with study activities placement of a continuous glucose monitor, IV catheter, and all blood draws.
4. Negative pregnancy test for all female subjects of childbearing age.
5. Signed informed consent by the subject or parent/guardian of minors.
6. All females of childbearing age and all sexually active males must agree to use an acceptable method of contraception throughout the study. Appropriate contraceptive methods include hormonal contraceptives (oral, injected, implanted, or transdermal), tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier methods. Abstinence is an acceptable form of birth control, though appropriate contraception must be used if the subject becomes sexually active.
7. Willing and able to adhere to requirements for maintaining continuous glucose monitoring.

Exclusion Criteria:

1. Use of any investigational drug within 30 days of Day 1.
2. Active infection (viral or bacterial) or any other intercurrent condition as reported by the subject or noted on physical exam at screening.
3. Any clinical or laboratory abnormality of Grade 3 or greater severity according to the CTCAE v5.0, or Grade 3 elevations in liver enzymes, defined as levels 5-20 times ULN in alanine aminotransferase (ALT/SGPT), or aspartate aminotransferase (AST/SGOT) in a clinically stable subject.
4. Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at increased risk by participating in this study.
5. Use of any medication known to significantly affect renal clearance (e.g., probenecid) or to increase protein catabolism (e.g., corticosteroids), or other medication known to increase ammonia levels (e.g., valproic acid or haloperidol), within the 48 hours prior to Day 1 and throughout the study.
6. Subjects with renal insufficiency will be excluded from the study. Cutoff eGFR \<60 mL/min/1.73m2 (GFR categories G3a-G5) will be used as measure of renal insufficiency.
7. Use of sodium benzoate within one week of Day 1.
8. Known hypersensitivity to PAA or PBA.
9. Breastfeeding or lactating females.
10. Subjects at risk of hypokalemia due to pre-existing diagnosis or on medications that can cause hypokalemia.
11. Subjects with type 1 or type 2 diabetes, or who take medications as part of their routine care that can cause hypoglycemia
12. A positive urine drug screen at screening for drugs without a prescription
13. Subjects who are taking medications in the antimetabolite drug class (e.g., hydroxyurea, 5-fluorouracil (5-FU), methotrexate) will be excluded; these medications can interfere with the DEXCOM sensor and cause inaccurate glucose readings

Where this trial is running

Pittsburgh, Pennsylvania

• UPMC Children's Hospital of Pittsburgh — Pittsburgh, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Gerard Vockley, MD, PhD — UPMC Children's Hospital of Pittsburgh
• Study coordinator: Elizabeth McCracken

Conditions Medium-chain Acyl-CoA Dehydrogenase Deficiency