Triheptanoin for MCADD

Overseen By Elizabeth McCracken, MS, CGC

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Jerry Vockley, MD, PhD

Must not be taking: Investigational drugs, Pancreatic lipase inhibitors

Disqualifiers: Active infection, Liver disease, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 9 weeks

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a medical research study to test a medication in adult patients with a disease called medium-chain acyl-CoA dehydrogenase deficiency (MCADD). The medication is triheptanoin, which is currently FDA approved for the treatment of Long-Chain Fatty Acid Oxidation Disorders. Previous research suggests that triheptanoin may also be effective in the treatment MCADD. This study will investigate the safety and efficacy (how well it works) of triheptanoin in patients with MCADD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using a pancreatic lipase inhibitor or medications that can cause low blood sugar. It's best to discuss your specific medications with the trial team.

What data supports the idea that the drug Triheptanoin for MCADD is an effective treatment?

The available research does not provide any data on Triheptanoin for MCADD. Instead, it focuses on treatments for eye conditions like macular edema and age-related macular degeneration. Therefore, there is no information here to support the effectiveness of Triheptanoin for MCADD. ^{1 2 3 4 5}

Research Team

Gerard Vockley, MD, PhD

Principal Investigator

UPMC Children's Hospital of Pittsburgh

Eligibility Criteria

Adults over 16 with MCADD, able to stay overnight for study activities at UPMC Children's Hospital Pittsburgh. Participants must not be pregnant or breastfeeding, agree to use contraception, and have no liver disease or diabetes. They can't have used investigational drugs recently or take meds that affect blood sugar levels.

Inclusion Criteria

I can stay overnight at the hospital, have an IV placed, and undergo blood tests.

I agree to use effective birth control or practice true abstinence during the study.

I am not pregnant.

Exclusion Criteria

I do not have any active infections or other ongoing health issues.

I have pancreatic insufficiency or I'm taking medication that affects fat absorption.

Pregnant, planning to become pregnant, breastfeeding or lactating females

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive triheptanoin with dose escalation from 0.2 gm/kg/day to 1.0 gm/kg/day, with three overnight admissions and fasting procedures

9 weeks

3 visits (in-person, overnight)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a phone call to check for adverse effects

1 week

1 visit (phone call)

Treatment Details

Interventions

• Triheptanoin

Trial Overview The trial is testing Triheptanoin in adults with MCADD to see if it's safe and effective. Triheptanoin is already approved for other metabolic disorders but might help prevent low blood sugar in MCADD too.

Participant Groups

Group I: Triheptanoin Experimental Treatment 1 Intervention

Open label study

Triheptanoin is already approved in United States for the following indications:

Approved in United States as Dojolvi for:

• Long-chain fatty acid oxidation disorders (LC-FAOD)

Who Is Running the Clinical Trial?

Jerry Vockley, MD, PhD

Lead Sponsor

Trials

6

Recruited

460+

Ultragenyx Pharmaceutical Inc

Industry Sponsor

Trials

94

Recruited

104,000+

Dr. Emil D. Kakkis

Ultragenyx Pharmaceutical Inc

Chief Executive Officer since 2010

MD/PhD in Biological Chemistry from UCLA

Dr. Eric Crombez

Ultragenyx Pharmaceutical Inc

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Findings from Research

In a study of 20 patients with chronic non-infectious uveitis and cystoid macular edema, treatment with a 0.19 mg fluocinolone acetonide implant led to significant improvements in best corrected visual acuity and reductions in central retinal thickness over a follow-up period of 2.3 years.

The treatment was found to be safe, with a notable percentage of patients able to reduce or discontinue systemic corticosteroids and disease-modifying antirheumatic drugs, indicating its potential to lessen the need for other anti-inflammatory treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal fluocinolone acetonide 0.19 mg (Iluvien®) for the treatment of uveitic macular edema: 2-year follow-up of 20 patients. Studsgaard, A., Clemmensen, KØ., Nielsen, MS.[2022]

Intravitreal triamcinolone acetonide (TA) effectively resolved cystoid macular oedema (CMO) in all 12 patients with refractory cases, with a mean follow-up of 40.5 months showing significant visual acuity improvements in 75% of patients.

While 41.6% of patients experienced ocular hypertension as a side effect, the treatment remains a viable option for managing resistant uveitic CMO, with the possibility of maintaining response through additional steroid injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal triamcinalone acetonide for refractory uveitic cystoid macular oedema: longterm management and outcome. Angunawela, RI., Heatley, CJ., Williamson, TH., et al.[2013]

In a pilot study of six patients with inflammatory cystoid macular oedema (CMO) resistant to other treatments, a single intravitreal injection of triamcinolone resulted in clinical and angiographic resolution of CMO for up to 6 months.

While the treatment was effective, five patients experienced increased intraocular pressure, and two developed cataracts, highlighting the need for monitoring and further research on the safety profile of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in uveitis. Young, S., Larkin, G., Branley, M., et al.[2022]

In a 2-year study involving 100 participants, adding intravitreal triamcinolone acetonide (ITA) to photodynamic therapy (VPDT) did not significantly improve visual acuity compared to VPDT alone, with both groups experiencing a loss of letters read.

However, the combination therapy with ITA resulted in fewer required retreatments (1.28 vs 1.94), indicating a potential benefit in reducing treatment frequency, although it also led to a higher incidence of elevated intraocular pressure that was manageable with medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy and intravitreal triamcinolone for neovascular age-related macular degeneration: a randomized clinical trial. Maberley, D.[2018]

Intravitreal injections of preservative-free triamcinolone acetonide (Triesence) significantly improved visual acuity and reduced central macular thickness in patients with macular edema, with the most notable improvements observed at one month after treatment.

While there were some adverse events, primarily elevated intraocular pressure, these were manageable with antiglaucoma medications, and no serious complications like endophthalmitis were reported during the study involving 102 patients over a 6-month follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intravitreal Preservative-Free Triamcinolone Acetonide (Triesence) for Macular Edema. Chang, AA., Li, H., Broadhead, GK., et al.[2015]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Intravitreal fluocinolone acetonide 0.19 mg (Iluvien®) for the treatment of uveitic macular edema: 2-year follow-up of 20 patients. [2022]

2. Denmark pubmed.ncbi.nlm.nih.gov

Intravitreal triamcinalone acetonide for refractory uveitic cystoid macular oedema: longterm management and outcome. [2013]

3. Australia pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in uveitis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Photodynamic therapy and intravitreal triamcinolone for neovascular age-related macular degeneration: a randomized clinical trial. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intravitreal Preservative-Free Triamcinolone Acetonide (Triesence) for Macular Edema. [2015]