A phase 2, open-label long-term extension study in participants with Duchenne muscular dystrophy amenable to exon skipping to assess the long-term safety, tolerability, pharmacokinetics, and efficacy of endosomal escape vehicle phosphorodiamidate morpholino oligomer platform products (ELEVATE-LTE)
| ISRCTN | ISRCTN31690502 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN31690502 |
| Integrated Research Application System (IRAS) | 1013685 |
| Sponsor's protocol code number | ENTR-601-DMD-202 |
| Sponsor | Entrada Therapeutics, Inc |
| Funder | Entrada Therapeutics |
- Submission date
- 03/03/2026
- Registration date
- 01/07/2026
- Last edited
- 01/07/2026
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Genetic Diseases
Plain English summary of protocol
Background and study aims
This long-term extension (LTE) is an open-label study following the initial ENTR-601-44-201 (ELEVATE-44; https://www.isrctn.com/ISRCTN15088415) and ENTR-601-45-201 (ELEVATE-45; https://www.isrctn.com/ISRCTN18511908) studies. There is no control or placebo (a dummy comparison drug). All participants will receive the active study drug at the same dose they were receiving upon completion of the initial study. This long-term extension study looks at the investigational medicines ENTR-601-44 and ENTR-60145 in participants with a rare genetic condition, Duchenne muscular dystrophy (DMD).
Changes in the genes, called variants, can alter the production of certain proteins. As a result of one or more changes to the DMD gene, the body produces little or a non-working dystrophin, a protein needed to help muscle function correctly. ENTR-601-44 and ENTR-601-45 are exon skipping therapies that aim to help the body ‘skip over’ the relevant variant so that the body can produce a shorter but working form of dystrophin.
The researchers will test over a period of time how safe ENTR-601-44 and ENTR-601-45 are, learn about any side effects, and look at the potential positive effects of ENTR-601-44 and ENTR-601-45.
Who can participate?
Males who have completed their participation in clinical study ENTR-601-44- 201 or ENTR-601-45-201.
What does the study involve?
In this summary, ENTR-601-44 and ENTR-601-45 are both called study medications. The study medication will be given as an intravenous infusion (slow injection) into a vein. Participants will receive a fixed number of doses of the study drug.
What are the possible benefits and risks of participating?
Participants may or may not benefit from this study. Participation could help increase knowledge about DMD and the study medication. The possible benefit of receiving ENTR-601-44 or ENTR-601-45 for participants is that dystrophin production may increase and improve muscle function, but there is no guarantee this will happen. This is an early study of ENTR-601-44 and ENTR-601-45 in individuals with DMD, and therefore, information on its potential positive effects in people is limited.
There is a risk that participants may have side effects while participating in the study. Participants might have side effects related to the study medication or study procedures while taking part in the study that could make them feel unwell, uncomfortable, or cause harm. The study staff will take measures to reduce the potential risks. Everyone taking part in the study will be watched for any side effects; however, the study staff does not know all the effects that the study medication may have on the participants. These effects may be mild or serious. In some cases, these effects might be long-lasting or permanent and may even be life-threatening. The study staff may give participants medicines to help reduce any side effects. Participants are advised to report anything to their study doctor that is bothersome or concerning for them.
Since this is an early study with the medication in humans, there is limited information on side effects. There have been studies done in laboratories on animals, there has been one other study on healthy men, and there have been studies with similar medicines. From this research, possible side effects might include issues with kidney function, blood clotting, blood cell count, and liver enzymes. There could also be side effects from the medication administration and muscle biopsies. However, researchers do not know all the side effects that could happen.
Where is the study run from?
Entrada Therapeutics, Inc, USA.
When is the study starting and how long is it expected to run for?
August 2026 to March 2032.
Who is funding the study?
Entrada Therapeutics, Inc, USA.
Who is the main contact?
clinicaltrials@entradatx.com
Contact information
Public, Scientific
1 Design Center, Place Suite 17-500
Boston
02210-2349
United States of America
| clinicaltrials@entradatx.com |
Principal investigator
Dep of Paediatrics Level 2 Children's Hospital, John Radcliffe, Headley Way, Headington
Oxford
OX3 9DU
United Kingdom
| Phone | +44 7423 213373 |
|---|---|
| laurent.servais@paediatrics.ox.ac.uk |
Public, Scientific
Vintners Place, 68 Upper Thames Street
London
EC4V 3BJ
United Kingdom
| UK-regulatory@medpace.com |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | N/A: single arm study |
| Masking | Open (masking not used) |
| Control | Uncontrolled |
| Assignment | Single |
| Purpose | Treatment, Safety |
| Scientific title | A phase 2, open-label long-term extension study in participants with Duchenne muscular dystrophy amenable to exon skipping to assess the long-term safety, tolerability, pharmacokinetics, and efficacy of endosomal escape vehicle phosphorodiamidate morpholino oligomer platform products (ELEVATE-LTE) |
| Study acronym | ELEVATE-LTE |
| Study objectives | Primary objective: To evaluate the long-term safety and tolerability of study drug in participants with DMD Secondary objectives: 1. To characterize the pharmacokinetics (PK) of study drug in participants with DMD after long-term dosing 2. To evaluate the impact of study drug on measures of function in participants with DMD after long-term dosing 3. To evaluate the immune response to study drug in participants with DMD after long-term dosing |
| Ethics approval(s) |
Approved 27/04/2026, South Central - Berkshire Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; -; berkshire.rec@hra.nhs.uk), ref: 26/SC/0088 |
| Health condition(s) or problem(s) studied | Duchenne muscular dystrophy |
| Intervention | Participants with DMD who completed either clinical study ENTR-601-44-201 or ENTR-601-45-201 will receive study medication administered intravenously (IV) every 6 weeks for 24 months (ie, ENTR-601-44 for participants continuing from Study ENTR-601-44-201 and ENTR-601-45 for participants continuing from Study ENTR-601-45-201). Participants enrolling in ENTR-601-DMD-202 will begin the LTE at the dose level they received upon completion of the open-label portion of the parent study. Dose escalation in the LTE study may be permitted based on emerging safety and efficacy data from the parent studies. After review of the cohort’s benefit-risk profile, participants may escalate to the higher dose that is deemed favourable compared with the preceding dose. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | ENTR-601-44, ENTR-601-45 |
| Primary outcome measure(s) |
To evaluate the long-term safety and tolerability of study drug in participants with DMD assessed by monitoring adverse events, physical examination, electrocardiogram (ECG) parameters, vital signs and clinical laboratory tests. From parent study baseline through End of Study (up to 2 years). |
| Key secondary outcome measure(s) |
1. To characterise the pharmacokinetics (PK) of study medicine in participants with DMD after long-term dosing by measuring the plasma concentration of study drug compounds and their final metabolite from parent study baseline through End of Study (up to 2 years) |
| Completion date | 31/03/2032 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | All |
| Lower age limit | 0 Years |
| Upper age limit | 120 Years |
| Sex | Male |
| Target sample size at registration | 80 |
| Key inclusion criteria | 1. Willing and able to provide consent (if at the age of majority) or assent (if a minor), as required by local regulations or the institutional review board (IRB)/independent ethics committee (IEC) after the nature of the study has been explained and prior to the performance of any study-related procedures 2. For participants under the legal age of consent, parent(s) or guardian(s) must be willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to the performance of any study-related procedures. Adult participants must be willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to the performance of any study-related procedures. Participants who reach the age of majority in their country while the study is ongoing will be asked to provide their own written consent again upon reaching the legal age of majority. 3. Participant completed clinical study ENTR-601-44- 201 or ENTR-601-45-201 4. Males who are sexually active with a female partner of childbearing potential must agree to use condoms during sexual intercourse. |
| Key exclusion criteria | 1. Any change from the applicable parent study eligibility criteria, including safety events during the parent study, that in the opinion of the investigator in consultation with the medical monitor and/or sponsor designee precludes safe use of study drug. 2. Participant has a condition or circumstance that in the view of the investigator places the subject at high risk of poor treatment compliance or for not completing the study. |
| Date of first enrolment | 03/08/2026 |
| Date of final enrolment | 18/08/2029 |
Locations
Countries of recruitment
- United Kingdom
- England
- Belgium
- Italy
- Netherlands
- Spain
Study participating centres
Headington
Oxford
OX3 9DU
England
London
WC1N 3JH
England
Newcastle upon Tyne
NE1 4LP
England
West Derby
Liverpool
L12 2AP
England
Leeds
LS1 3EX
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
03/03/2026: Trial's existence confirmed by NHS HRA.
