A Phase 1b Open Label Study of REN001 in McArdle Disease
Research type
Research Study
Full title
A PHASE 1B, OPEN-LABEL STUDY TO EVALUATETHE SAFETY AND TOLERABILITY OF 12 WEEKS TREATMENT WITH ORAL REN001 IN PATIENTS WITH MCARDLE DISEASE (GLYCOGEN STORAGE DISORDER TYPE 5)
IRAS ID
263201
Contact name
Lynn Purkins
Contact email
Sponsor organisation
Reneo Pharma Ltd
Eudract number
2019-001349-42
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Research Summary
This is an open-label, Phase 1b study of the safety and tolerability of 12-weeks treatment with 100mg REN001 in subjects with McArdle disease.
Primary Objective:
To evaluate the safety and tolerability of REN001 in subjects with McArdle Disease during 12 weeks of treatment.Pharmacokinetic Objectives:
To investigate pharmacokinetics of REN001 in subjects with McArdle Disease treated for 12 weeks with REN001, administered as a capsule, using population pharmacokinetic methodology.Exploratory Objectives:
To evaluate the effect of REN001 on clinical outcome measures in subjects with McArdle Disease treated for 12 weeks.
To explore the effects of REN001 on quality of life measures in subjects with McArdle Disease treated for 12 weeks.
To explore the change from Screening to Week 12 in Acylcarnitine profile.Summary of Results
• A multicenter study that evaluated the safety and tolerability of REN001 in subjects with McArdle disease. This was an open-label study with all subjects receiving 100 mg REN001 as 2 x 50 mg oral capsules once daily for 12 weeks.
• Although the study was designed to determine the safety, tolerability, and pharmacokinetic profile of dosing with REN001, exploratory outcome measures were included to ascertain the appropriate measures to be used in future clinical development.
• Approximately 24 subjects were planned to be screened to achieve 19 subjects dosed with REN001.
• Twenty-two subjects were screened and 18 subjects were dosed with REN001.
• As some subjects were re-screened and 1 subject participated in the dosing phase twice, there were 19 unique subjects screened and 17 unique subjects who were dosed with REN001.
• The planned duration of the study for each subject was approximately 18 weeks (assuming up to 4 weeks screening, 12 weeks of treatment, and 2 weeks of follow-up). The study closed when all subjects had completed the Follow-up Visit and the subsequent adverse event (AE) follow-up telephone call (30 days after last study treatment).
• Fifteen of the 18 subjects dosed completed the study; 1 of these had their Week 12 Visit after 10 weeks of dosing due to the ensuing Coronavirus disease 2019 (COVID-19) pandemic. Three subjects withdrew from the study due to the pandemic. One of the subjects who withdrew had completed 10 weeks of dosing but was unable to attend an early Week 12 Visit; consequently, they were re-enrolled and completed a further 12 weeks of dosing. The remaining 2 subjects did not re-enroll.
• In this study REN001 was safe and well tolerated with no SAEs or TEAEs leading to study withdrawal, nor any other significant safety findings.
• REN001 plasma concentrations increased after dosing to a maximum median value of 5,970 ng/mL at 2 hours postdose on Day 1 and 5,900 ng/mL at 4 hours postdose on Week 12.
• Overall there were no meaningful changes from baseline in any of the exploratory assessments conducted including patient-reported outcomes. However, importantly, an increase in mean fat oxidation (38.47%), as measured by indirect calorimetry, was observed. This increase was corroborated by a mean decrease in the RER in the submaximal exercise test. The increase in fat oxidation observed is consistent with the REN001 mechanism of action. However, the improvement in fat oxidation did not translate to improvements in muscle symptoms or quality of life in this population of relatively fit and asymptomatic patients with McArdle disease.REC name
London - Fulham Research Ethics Committee
REC reference
19/LO/0819
Date of REC Opinion
29 May 2019
REC opinion
Favourable Opinion