Phase 1 of Single Intravenous Infusion of Ascending Doses of ENTR-601-44 in Healthy Male Volunteers

• Research type

  Research Study

• Full title

  Phase 1 Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Infusion of Ascending Doses of ENTR-601-44 in Healthy Male Volunteers

• IRAS ID

  1007814

• Contact name

  Bhavna Patel-Shah

• Sponsor organisation

  Entrada Therapeutics, Inc.

• ISRCTN Number

  ISRCTN36174912

• Research summary

  Research Summary\n\nThe purpose of this study is to test an investigational (unapproved) drug called ENTR-601-44 (the ‘study drug’) that is being developed for the treatment of Duchenne muscular dystrophy (DMD).\nDuchenne muscular dystrophy is a genetic disease that occurs mostly in males. Duchenne muscular dystrophy is caused by mutations in the DMD gene that interrupt the production of a functional dystrophin protein. As dystrophin is important for muscle health and function, people with these mutations experience muscle weakness that gets worse over time. Eventually, patients with DMD lose the ability to walk and breathe. The average age of death in patients with DMD is in the early 30s.\nThe main aims of this study are:\n•\tTo assess the safety and tolerability of the study drug\n•\tTo see how the body absorbs and removes the study drug\n•\tTo assess the effect of the study drug on the body\nIt is planned to enrol 40 participants into the study, who will be divided into 5 groups, consisting of 8 participants each. In each group, 6 participants will receive the study drug and 2 participants will receive placebo. Therefore, participants have a 3 in 4 (75%) chance of receiving the study drug and a 1 in 4 (25%) chance of receiving placebo.\nHealthy males aged between 18 to 55 years and who are likely to match all the other characteristics required to enter this study will be invited to take part.\n\nSummary of Results\n\nPhase 1 Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Infusion of Ascending Doses of ENTR-601-44 in Healthy Male Volunteers MAC Number: MAC175 Protocol Number: ENTR-601-44-101\n\nThis study was organised and funded by Entrada Therapeutics (the ’Sponsor’) and was run by MAC Clinical Research in Manchester, UK from August 2023 to June 2024.\n\nWhy was this study conducted?\nThe purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics (PK; how the body absorbs and removes the study drug) of four doses of a new medicine called ENTR-601-44 given to healthy male participants. ENTR-601-44 was administered as a single intravenous (IV) dose, which is a controlled flow of the study medication directly into the bloodstream over a certain amount of time, to determine if it causes any side effects by comparing its results with a placebo. A placebo looks like the study medicine but does not contain any active ingredients. ENTR-601-44 is being investigated as a potential treatment for Duchenne muscular dystrophy (DMD).\nDuchenne muscular dystrophy is a rare neuromuscular genetic disorder that affects the muscles. Duchenne muscular dystrophy is caused by changes in the DMD gene that make it harder for the body to produce a certain protein called dystrophin. Dystrophin is important for muscle health and function. There is currently no cure for DMD, and current treatment options often have unwanted side effects and do not address the root cause of the disease, which is genetic.\nENTR-601-44 works by a process called exon skipping, which is a natural process that helps the body to skip over missing pieces of the genetic code. Exon skipping can allow a slightly shorter but functional dystrophin protein to be formed. ENTR-601-44 is designed to increase this process in the missing sections of genetic code. The production of a functional dystrophin protein is key in making sure the muscle cells work as they should, and in patients with DMD, this has the potential to relieve some symptoms and may result in a milder course of the disease.\n\nThe main aims of the study were to assess:\n* the safety and tolerability of ENTR-601-44 at 4 different dose levels.\n* how the body absorbs and removes ENTR-601-44.\nThis study was the first time the study drug was given to humans. Prior to this study, the study drug was tested in animals.\n\nWho took part in the study?\n33 healthy male participants were enrolled onto the study; 32 participants were dosed and completed the study. Participants were split into 4 groups consisting of 8 participants each. In each group, 6 participants received ENTR-601-44 and 2 participants received placebo. Each group received a different dose level of ENTR-601-44:\n* Group 1 - 0.75 mg/kg\n* Group 2 - 1.5 mg/kg\n* Group 3 - 3.0 mg/kg\n* Group 4 - 6.0 mg/kg\n\nWhat happened during the study?\nParticipants attended the clinic for a Screening visit where they had various health checks to confirm they were eligible to participate in the study.\nEligible participants checked into the clinic 1 day before they were due to receive the study medication (Day-1). After receiving the study medication on Day 1, participants completed additional safety tests and stayed in the clinic for a further 6 nights. Participants were discharged from the clinic on Day 7. Following discharge, participants returned to the clinic for a further 3 follow-up visits (Day 14, Day 21 and Day 28; each for a single overnight stay) for further safety tests. A final outpatient visit to the clinic on Day 42 marked the end of the study.\nSafety tests included vital signs (blood pressure, body temperature, breathing rate and heart rate measurements), electrocardiogram (ECG) monitoring (recording the electrical activity of the heart), physical examination (a medical check-up by the study doctor) and urine and blood tests. A muscle biopsy was also performed once during the study to check the levels of the study drug and look at the effect it had on the muscle.\nThe maximum length of participation in this study was approximately 10 weeks.\n\nWhat were the overall results of the study?\nOverall, ENTR-601-44 was found to be safe and well tolerated.\nSide effects are unwanted medical issues during the study that may or may not be related to the study drug. Some participants in this study experienced side effects, but no serious side effects or safety concerns were reported. Headaches were the most common side effect in this study.\nThere were no important changes in urine and blood test results (including kidney function tests) and no important changes or trends in vital signs, ECG readings or physical examinations.\nBased on the results of this study and data from the muscle biopsy taken in Group 4 at the 6.0 mg/kg dose of ENTR-601-44, it appears to show an increased level of exon skipping and thus demonstrated a small positive effect. Therefore 6.0 mg/kg ENTR-601-44 could be an effective and safe starting dose to use in future studies with individuals with DMD.\n\nHow has this study helped the researchers?\nThis study was in healthy males aged between 18 and 55 years old to investigate the safety and tolerability of ENTR-601-44 at 4 different dose levels, and to learn more about how ENTR-601-44 works in the body. The study results apply to the particular people that took part in the study and may not be true for everybody. The overall safety and tolerability profile, combined with the increased level of exon skipping seen at 6.0 mg/kg ENTR-601-44, supports further development of ENTR-601-44, including conducting a study in patients with DMD.\nWhere can I find more information about this study?\nTo learn more about this study, visit https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.nihr.ac.uk.%2FNBTI%2F_4W-AQ%2FAQ%2F27d9a89c-d863-42bc-862f-1a081f8dc476%2F1%2F-tc1mXUZFX&data=05%7C02%7Cwales.rec1%40wales.nhs.uk%7Cce5a46e66cd44f6c4d9c08ddf9a63807%7Cbb5628b8e3284082a856433c9edc8fae%7C0%7C0%7C638941214520755917%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=iApqXfVxYG4N8pBorjKvi%2B3ShEgKV8FO4d3Iv30aogQ%3D&reserved=0\nThis summary was completed on 11 August 2025. Newer information since this summary was written may now exist. This summary includes only results from one single study. Other studies may find different results.\n

• REC name

  Wales REC 1

• REC reference

  23/WA/0123

• Date of REC Opinion

  24 Jul 2023

• REC opinion

  Further Information Favourable Opinion