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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called triheptanoin (also known as Dojolvi or UX007) for individuals with medium-chain acyl-CoA dehydrogenase deficiency (MCADD), a genetic disorder affecting fat metabolism. Triheptanoin is already used for other similar metabolic disorders, and the study aims to determine its safety and effectiveness for MCADD. The trial is open-label, so all participants will know they are receiving the trial medication. It suits those with a confirmed MCADD diagnosis who can engage in study activities, such as overnight stays at a research facility for testing. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that triheptanoin is likely to be safe for humans?

Research has shown that triheptanoin is generally safe for people. One study found no major safety concerns requiring special precautions. The FDA has already approved triheptanoin for treating certain fatty acid disorders, indicating it is usually well-tolerated.

Another study examined the safety of triheptanoin in both adults and children. The results were positive, indicating it can be used without major problems. This should reassure those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MCADD?

Unlike the standard of care for Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD), which often involves dietary management and emergency protocols for managing metabolic crises, Triheptanoin offers a new approach. Triheptanoin is a synthetic triglyceride that provides an alternative energy source by bypassing the block in fatty acid oxidation. Researchers are excited about Triheptanoin because it has the potential to provide a constant energy supply, reducing the risk of metabolic crises and improving overall energy metabolism for patients with MCADD.

What evidence suggests that triheptanoin might be an effective treatment for MCADD?

Research has shown that triheptanoin, which participants in this trial will receive, may help individuals with conditions like medium-chain acyl-CoA dehydrogenase deficiency (MCADD). It already treats related metabolic issues known as long-chain fatty acid oxidation disorders. Triheptanoin provides an alternative energy source, boosting energy production in the body. Previous studies found it effective in managing symptoms for individuals with similar metabolic disorders. There is hope it could also benefit those with MCADD, but further research is necessary to confirm this. ^{1 3 6 7 8}

Who Is on the Research Team?

Gerard Vockley, MD, PhD

Principal Investigator

UPMC Children's Hospital of Pittsburgh

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07097311

NCT07097311 | Study to Evaluate the Use of Triheptanoin ... Previous research suggests that triheptanoin may also be effective in the treatment MCADD. This study will investigate the safety and efficacy ( ...

2. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/213687Orig1s000RiskR.pdf

213687Orig1s000 - accessdata.fda.gov This review evaluates whether a risk evaluation and mitigation strategy (REMS) for Dojolvi (triheptanoin).

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1096719223003190

Heptanoic and medium branched-chain fatty acids as ... Triheptanoin (triheptanoylglycerol) has shown value as anaplerotic therapy for patients with long chain fatty acid oxidation disorders but is contraindicated ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01886378?term=AREA%5BExpandedAccessNCTId%5DNCT03773770&rank=5

A Study of UX007 (Triheptanoin) in Participants With Long- ... Diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, short- or medium-chain FAOD, ketone body metabolism defect, propionic acidemia or ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5234721/

Triheptanoin: long-term effects in the very long-chain acyl- ... Deficiency of one of the enzymes involved is associated with life-threatening events and death. Very-long chain acyl-CoA dehydrogenase (VLCAD) deficiency (OMIM ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK598998/

Clinical Review - Triheptanoin (Dojolvi) - NCBI Bookshelf Study CL201 (N = 29) was a multi-centre, open-label, single-arm phase II study investigating the efficacy and safety of triheptanoin in adults and children (6 ...

7. dojolvihcp.com dojolvihcp.com/

DOJOLVI® (triheptanoin) | LC Fatty Acid Oxidation Disorder DOJOLVI® (triheptanoin) is the first and only FDA approved treatment for patients diagnosed with long chain fatty acid oxidation disorders (LC-FAOD)

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK1424/

Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Risk stratification by residual enzyme activity after newborn screening for medium-chain acyl-CoA dehyrogenase deficiency: data from a cohort study.