In short
ENTR-601-45 is an investigational nucleic acid-based therapy being studied for Duchenne muscular dystrophy (DMD) in people amenable to exon 45 skipping. It is given by intravenous infusion and has no marketing authorisation. Two authorised trials are currently listed in the EU Clinical Trials Information System, with a combined planned enrollment of 118 participants across Phase 1/2 and Phase 2 studies.
Key points
- ENTR-601-45 is an investigational therapy for Duchenne muscular dystrophy amenable to exon 45 skipping.
- The main study is a Phase 1/2 randomised, placebo-controlled trial with 38 planned participants.
- A second Phase 2 open-label extension study plans to enroll 80 participants.
- Both trials measure safety and tolerability as their primary outcomes.
- ENTR-601-45 is given by intravenous infusion as a solution for infusion.
- The therapy aims to increase dystrophin protein production in muscles.
What is ENTR-601-45?
ENTR-601-45 is an investigational nucleic acid-based substance developed by Entrada Therapeutics, Inc. It is being studied for Duchenne muscular dystrophy (DMD) in people whose genetic mutation is amenable to exon 45 skipping. The substance is classified in the therapeutic area of musculoskeletal diseases. ENTR-601-45 has no marketing authorisation in the product records, meaning it has not been approved as a medicine. It is part of a platform of endosomal escape vehicle phosphorodiamidate morpholino oligomer products, a type of exon-skipping therapy.
How does ENTR-601-45 work?
ENTR-601-45 is designed to increase dystrophin protein production in muscles. Dystrophin is a protein that helps muscles function properly, and people with Duchenne muscular dystrophy have little or no functional dystrophin. The therapy uses exon skipping, a technique that allows the body to produce a shorter but still functional version of the dystrophin protein. ENTR-601-45 specifically targets exon 45 of the dystrophin gene, making it suitable only for people whose mutation can be addressed by skipping this exon.
Which conditions is ENTR-601-45 studied for?
- Duchenne muscular dystrophy — a genetic muscle-wasting condition that mainly affects boys and leads to progressive muscle weakness. ENTR-601-45 is being studied only in people whose DMD mutation is amenable to exon 45 skipping.
How is ENTR-601-45 given?
ENTR-601-45 is given as a solution for infusion by intravenous infusion. In the long-term extension study, the dose of ENTR-601-45 is reported as 20 mg per kilogram of body weight. The trial records also list sodium chloride as an intravenous infusion, which serves as the placebo or comparison arm in the randomised study.
What do the clinical trials show?
Two authorised trials of ENTR-601-45 are listed in the EU Clinical Trials Information System. One trial is a Phase 1/2 randomised, double-blind, placebo-controlled study called ELEVATE-45, with 38 planned participants. The second is a Phase 2 open-label long-term extension study called ELEVATE-LTE, with 80 planned participants. Both studies are interventional and focus on safety and tolerability as their primary outcomes. The ELEVATE-45 study has two parts: Part A assesses safety, tolerability, pharmacokinetics (how the drug moves through the body) and pharmacodynamics (how the drug affects the body), while Part B evaluates safety and efficacy. Participants in Part A of ELEVATE-45 have a 75% chance of receiving ENTR-601-45 and a 25% chance of receiving placebo. Both trials measure treatment-emergent adverse events, vital signs, clinical laboratory results, electrocardiogram (ECG) parameters and physical examination findings as primary outcomes.
What side effects are known?
The trials are designed to identify side effects, and the primary outcomes include the incidence and severity of treatment-emergent adverse events. The research summary states that the study aims to identify any side effects of ENTR-601-45. No specific side effects have been reported in the available sources, as the trials are still in early phases and results have not been published.