Principal Investigator: Nicola Longo
Keywords: Fatty Acid Oxidation Disorders , FAOD , REN001-102 Department: Pediatric Genetics
IRB Number: 00121194
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Recruiting

Contact Information

Carrie Bailey

Brief Summary

This is an open-label, multiple-dose Phase 1 study of the safety and tolerability of 2 dose levels of REN001 in subjects with fatty acid oxidation disorders (FAODs). Patients should have a confirmed FAOD due to mutations in the CPT2, VLCAD, LCHAD, or TFP proteins to be eligible for the study.



  • To evaluate the safety and tolerability of 12 weeks treatment with REN001 in subjects with FAOD.

Pharmacokinetics Objective:

  • To investigate pharmacokinetics of REN001 in subjects with FAOD treated for 12 weeks with REN001.

Pharmacodynamic Objective:

  • To investigate the pharmacodynamics effects of REN001 in subjects with FAOD treated for 12 weeks.

Exploratory Objectives:

  • To explore the effect of 12 weeks treatment of REN001 on potential clinical outcome measures in subjects with FAOD.
  • To explore the effects of REN001 on quality of life measures in subjects with FAOD treated for 12 weeks.

Inclusion Criteria

  1. Males and females aged 18 years or older.
  2. Confirmed diagnosis of one of the following:
    1. Carnitine palmitoyltransferase II deficiency (CPT2)
    2. Very long-chain Acyl-CoA dehydrogenase deficiency (VLCAD)
    3. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD)
    4. Trifunctional protein deficiency (TFP)
  3. A diagnostic acylcarnitine profile, in blood or cultured fibroblasts.
  4. Genotyping with at least 1 allele that is not a stop codon or a frame shift. If no confirmed genotyping is available genotyping can be conducted as part of the screening process.
  5. Have evidence of any one of the following clinical manifestations despite therapy:
    1. Chronic elevated CPK in the last 3 years as evidenced by at least 2 blood CPK levels above the upper limit of normal (ULN) obtained at least 3 months apart. NOTE: an elevated CPK level at screening can be used to fulfill this criterion
    2. History of cardiomyopathy
    3. A clinical event of hypoglycemia, rhabdomyolysis, or exacerbation of cardiomyopathy within the 12 months preceding enrollment
  6. Currently following a stable dietary regimen with avoidance of fasting as documented by a 3-day dietary record obtained during the screening period.
  7. A stable treatment regimen for at least 30 days prior to enrollment.
  8. Expected and willing to remain on stable diet and medication through the study.
  9. Ambulatory and able to perform the study exercise tests.
  10. Adequate kidney function defined as an estimated glomerular filtration rate (eGFR) defined as ≥60 mL/min/1.73 m2 using the MDRD formula
  11. Able to swallow capsules.
  12. Females should be either of non-child-bearing potential or must agree to use a highly effective method of contraception. Males with partners who are WOCBP must also use contraception from baseline.
  13. Willing and able to personally sign and date an informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

Exclusion Criteria

  1. Unstable or poorly controlled disease as determined by one or more of the following:
    1. Echocardiogram with evidence of active or worsening cardiomyopathy at screening
    2. Presence of symptoms of acute rhabdomyolysis with elevations in serum CPK consistent with acute exacerbation of myopathy
    3. Evidence of acute crisis from their underlying disease
  2. Currently taking anticoagulants.
  3. Currently taking or anticipated to need a PPAR agonist during the study.
  4. Have motor abnormalities other than those related to the fatty acid oxidation disorder that could interfere with the outcome measures.
  5. Treatment with an investigational drug within 1 month or within 5 half-lives, whichever is longer.
  6. Evidence of significant concomitant clinical disease that in the opinion of the Investigator may need a change in management during the study or could interfere with the conduct or safety of this study. (Stable well-controlled chronic conditions such as controlled hypertension (BP<140/90 mmHg) thyroid disease, well-controlled Type 1 or Type 2 diabetes (HbA1c< 8%), hypercholesterolemia, gastroesophageal reflux, or depression under control with medication (other than tricyclic antidepressants), are acceptable provided the symptoms and medications would not be predicted to compromise safety or interfere with the tests and interpretations of this study).
  7. History of cancer with the exception of in situ skin cancer.
  8. Have been hospitalized within the 3 months prior to screening for any major medical condition (as deemed by the primary investigator).
  9. Any condition possibly reducing drug absorption (e.g., gastrectomy).
  10. History of clinically significant liver disease as evidenced by elevations in ALT, GGT or TB.  Subjects with modestly elevated bilirubin (e.g. < 2xULN) may be included after discussion with the Medical Monitor if the cause is due to a benign hereditary disorder of metabolism such as Gilbert’s syndrome.
  11. Positive hepatitis B surface antigen (HBsAg) or hepatitis C, or HIV at screening.
  12. Pregnant or nursing females.
  13. History of sensitivity to PPAR agonists.
  14. Donation or intent to donate blood, or blood components during the study or within one month after completion of the study.
  15. History of illicit drug abuse or with a positive urine drug screen including a positive for cannabis in states where cannabis use is legalized. Positive results for opiates and/or benzodiazepines will only be allowed if supported by a corresponding prescription from a medically qualified person.
  16. History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of spirits) within 6 months of screening.
  17. Inability to comprehend or unwilling to follow the study requirements including restrictions on treatments, attendance at out-subject clinic visits, completion of questionnaires and participation in laboratory testing as called for by the protocol.
  18. Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the Investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results.
  19. Currently taking drugs with a narrow therapeutic index and P-glycoprotein/Breast Cancer Resistance Protein (P-gp/BCRP) mediated absorption, distribution, metabolism and excretion (ADME) e.g., aliskiren, ambrisentan, colchicine, digoxin, everolimus, imatinib, lapatinib, maraviroc, nilotinib,  posaconazole, ranolazine, saxagliptin, sirolimus, sitagliptin, talinolol, tolvaptan, topotecan, methotrexate, mitoxantrone, irinotecan, rosuvastatin, and sulfasalazine.
  20. Subjects who are not eligible or have a contraindication for cataract surgery.