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

A Phase 2, Open-Label, Fixed Dose Study to Evaluate the Use of Sodium Phenylbutyrate (ACER-001) in the Treatment of Pediatric and Adult Patients With MCAD Deficiency Caused by the Common ACADM c.985 A>G (K304E) Mutation

This study is testing if sodium phenylbutyrate can safely help people aged 10 and older with medium-chain acyl-CoA dehydrogenase deficiency feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 10 Years and up
• Sex: All
• Sponsor: University of Pittsburgh (Academic / other)
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT06069375 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of sodium phenylbutyrate (ACER-001) in patients aged 10 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 two overnight admissions and one outpatient visit over a total study duration of 7 weeks, during which they will fast and receive the study drug in varying doses. Blood samples will be collected to monitor the drug's effects and any potential adverse reactions.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 10 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 10 years of age may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with MCADD, potentially improving their health outcomes.

How similar studies have performed: Previous studies have suggested that sodium phenylbutyrate may be effective for MCADD, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* A diagnosis of MCADD and molecular confirmation of at least one copy of the common c.985A\>G mutation.
* ≥16 years of age for cohort 1 and ≥10-15 years of age for cohort 2.
* Able to perform and comply with study activities including overnight admission to the PCTRC, placement of an IV catheter, and all blood draws.
* Negative pregnancy test for all female subjects of childbearing age.
* Signed informed consent by the subject or parent/guardian of minors.
* 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.

Exclusion Criteria:

* Use of any investigational drug within 30 days of Day 1.
* Active infection (viral or bacterial) or any other intercurrent condition as reported by the subject or noted on physical exam at screening.
* 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), aspartate aminotransferase (AST/SGOT), or gamma glutamyl transpeptidase (GGT) in a clinically stable subject.
* 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.
* 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.
* 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.
* Use of sodium benzoate within one week of Day 1.
* Known hypersensitivity to PAA or PBA.
* Breastfeeding or lactating females.
* Subjects at risk of hypokalemia due to pre-existing diagnosis or on medications that can cause hypokalemia.
* Subjects with type 1 or type 2 diabetes, or who take medications as part of their routine care that can cause hypoglycemia

Where this trial is running

Pittsburgh, Pennsylvania

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

Study contacts

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

Conditions Medium-chain Acyl-CoA Dehydrogenase Deficiency; Medium Chain Acyl-CoA Dehydrogenase Deficiency