A non-interventional Long Chain Fatty Acid Oxidation Disorder study

• Research type

  Research Study

• Full title

  A prospective, multicenter, non-interventional study to investigate the disease characteristics of adult patients with long chain fatty acid oxidation disorders (FAOD)

• IRAS ID

  290009

• Contact name

  Mark Roberts

• Contact email

  markrob@doctors.org.uk

• Sponsor organisation

  Reneo Pharma Ltd.

• Clinicaltrials.gov Identifier

  NCT04482049

• Clinicaltrials.gov Identifier

  N/A, N/A

• Duration of Study in the UK

  1 years, 5 months, 29 days

• Research summary

  Research Summary
  This is multicenter, multinational, non-interventional, prospective study with the following objectives:
  1. To evaluate disease characteristics including functional and biochemical parameters in adult subjects with long-chain fatty acid oxidation disorders (FAOD)
  2. To evaluate symptoms related to FAOD using a newly developed muscle symptom questionnaire specifically designed for adult patients with long-chain FAOD

  The study will enroll approximately 90 individuals, 18 years and older at centers with expertise in evaluating and treating subjects with FAOD.

  Summary of Results
  This study was a 16-week, prospective, non-interventional study in LC-FAOD patients with various nDNA defects to better understand the natural history of LC-FAOD and changes in patient function and symptoms over time.

  Study Patients:

  A total of 58 patients participated in the study, including patients with defective long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD, n=16), carnitine palmitoyltransferase 2 (CPT2, n=30), or very long-chain acyl-CoA dehydrogenase (VLCAD, n=12).

  Mean age was 33.9 years (SD 13.3); gender was 57% males and 43% females.
  Mean (SD) changes in the 12-minute walk test (12MWT), 12-Item Short Form Health Survey (SF-12) vitality domain score, and Modified Fatigue Impact Scale (MFIS) total score for patients who completed both baseline and Week 16 assessments are summarized in Table 1. Symptom improvement is represented by an increase in SF-12 vitality score or a decrease in MFIS total score.
  Table 1. Mean (SD) Baseline and Week 16 Change by Subgroup
  12MWT (m) SF-12 Vitality MFIS Total
  n Baseline Change n Baseline Change n Baseline Change
  LCHAD 12 723.0
  (63.1) 11.9
  (26.7) 13 48.1
  (7.7) -1.9
  (6.6) 13 28.1
  (4.4) 2.3
  (2.9)
  CPT2 29 888.6
  (31.0) 24.4
  (12.8) 30 53.3
  (4.9) -2.5
  (4.9) 30 27.7
  (2.7) -2.4
  (1.9)
  VLCAD 11 818.1
  (35.2) 37.9
  (17.4) 12 45.8
  (6.0) -6.3
  (7.0) 12 33.8
  (3.7) 1.8
  (3.6)

  Safety Results:

  The most common adverse events experienced by patients were rhabdomyolysis (7 patients) and COVID-19 infection (5 patients); the majority of adverse events were mild or moderate in severity.

  Conclusions:

  • This study provides valuable information about disease characteristics, key safety events and the natural history of LC-FAOD in adults followed for 4 months
  • The increases in distance walked from baseline in the 12MWT are consistent with a learning effect, and lower than what would be expected for healthy individuals
  • The LCHAD population’s low mean SF-12 physical component score at baseline suggests that this population has more meaningful physical limitations than other LC-FAOD genotypes

  Both baseline values and changes from baseline observed at Month 4 in the 12MWT and SF-12 score support calculating performance of a placebo group in future interventional trials.

• REC name

  North West - Preston Research Ethics Committee

• REC reference

  20/NW/0418

• Date of REC Opinion

  30 Oct 2020

• REC opinion

  Favourable Opinion