Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Pediatric and Adults Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)

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 is a medical research study to test a medication in patients 4 years of age and older with a disease called medium-chain acyl-CoA dehydrogenase deficiency (MCADD) caused by the common ACADM c.985 A>G (K304E) mutation. The medication is sodium phenylbutyrate (ACER-001), which is currently FDA approved for the treatment of Urea Cyle Disorders. Previous research suggests that sodium phenylbutyrate may also be effective in the treatment MCADD. This study will investigate the safety and efficacy (how well it works) of sodium phenylbutyrate in patients with MCADD.

Study Overview

• Status: Recruiting
• Conditions: Medium-chain Acyl-CoA Dehydrogenase Deficiency
• Intervention / Treatment: Drug: Sodium phenylbutyrate

Detailed Description

Participation in the study will require three outpatient visits at the Clinical and Translational Research Center at the UPMC Children's Hospital of Pittsburgh (also called the PCTRC). The total length of the study participation is approximately 5 weeks.

Participants will come in for a screening visit (Visit 1) to where they will undergo some lab work testing to confirm they are eligible for the study. If it's determined that they are eligible, they will undergo training on the use of a continuous glucose monitor (CGM). They will be sent home and asked to wear the CGM for the next 10 days. This 10-day period is considered the run-in period.

Following the run-in period, participants will return to the site (Visit 2) in a fasting state. They will have an intravenous access line (IV) placed for several blood draws during the visit. Fasting labs will be drawn, then the participant will be provided with a meal and then will then be dosed with ACER-001. Following the dose of ACER-001, pharmacokinetics (PK) samples will be collected over the next 8 hours. Once the final PK sample has been collected, participant will be sent home with continuous glucose monitoring and will be asked to log their ACER-001 doses as well as overnight fasting times.

All participants will be dosed at 4.0 g/m2/day divided two times a day.

Participants will be asked to return approximately 2 weeks later for Visit 3 to complete the same procedures outlined for Visit 2.

Study staff will contact the participant by phone approximately 1 week after Visit 3 to follow up on any adverse events.

All study procedures will be done at no cost to the participants..

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elizabeth McCracken; Phone Number: 412-692-5662; Email: elizabeth.mccracken@chp.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • UPMC Children's Hospital of Pittsburgh
      • Principal Investigator: Gerard Vockley, MD, PhD
      • Contact: Elizabeth McCracken, MS, CGC; Phone Number: 412-692-5662; Email: elizabeth.mccracken@chp.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4.0 g/m2/day BID sodium phenylbutyrate; Up to 24 subjects (12: ages 4-9 years old; 12:10 years of age and older) will be randomized to take 4.0 g/m2/day divided into two daily doses	Drug: Sodium phenylbutyrate; Open-label design with doses of sodium phenylbutyrate at 4.0 g/m2/day; Other Names: Olpruva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment related adverse events as assessed by CTCAE v5.0	5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of time before glucose falls below 60 mg/dL	Comparison of the length of time each participant's glucose level stays above 60 mg/dL, comparing their values from the run-in period to the results obtained between Visits 2 and 3	5 weeks
Length of time before glucose falls below 70 mg/dL	Comparison of the length of time each participant's glucose level stays above 70 mg/dL, comparing their values from the run-in period to the results obtained between Visits 2 and 3	5 weeks
Length of time before glucose falls below 80 mg/dL	Comparison of the length of time each participant's glucose level stays above 80 mg/dL, comparing their values from the run-in period to the results obtained between Visits 2 and 3	5 weeks

Collaborators and Investigators

• Sponsor: Jerry Vockley, MD, PhD
• Collaborators: Zevra Therapeutics
• Investigators: Principal Investigator: Gerard Vockley, MD, PhD, UPMC Children's Hospital of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 9, 2025
• First Posted (Actual): January 14, 2025

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Medium-chain Acyl-CoA Dehydrogenase Deficiency
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Medium chain acyl CoA dehydrogenase deficiency; Antineoplastic Agents; 4-phenylbutyric acid
• Other Study ID Numbers: STUDY24100064

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No