A 2-part, randomized, double-blind, placebo-controlled study in participants with Duchenne muscular dystrophy amenable to exon 45 skipping to evaluate the safety and efficacy of ENTR-601-45 (ELEVATE-45)
| ISRCTN | ISRCTN18511908 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18511908 |
| EudraCT/CTIS number | 2024-517499-39 |
| IRAS number | 1010846 |
| Secondary identifying numbers | ENTR-601-45-201, CPMS 66105 |
- Submission date
- 28/12/2024
- Registration date
- 30/05/2025
- Last edited
- 01/07/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
The study aims to determine if ENTR-601-45 is safe, identify any side effects, and see how well it works on DMD by possibly increasing dystrophin protein production. Dystrophin helps muscles function properly. ENTR-601-45 is an investigational medication, meaning it has not been approved by the Medicines and Healthcare products Regulatory Agency (MHRA), the health authority that gives approval for new medications in the United Kingdom.
Who can participate?
This study is for ambulatory minors and adults aged 4 to 20 years old, inclusive, who were assigned male at birth, have a confirmed diagnosis of Duchenne muscular dystrophy, and have a genetic variant of the dystrophin gene that allows ENTR-601-45 to skip exon 45. People cannot take part if they have another ongoing disease or condition affecting the kidneys.
What does the study involve?
Participants will receive either ENTR-601-45 or a placebo (a substance with no active ingredients). At the end of the 25 weeks of the study, all participants (including those who received a placebo) may be able to receive ENTR-601-45 in a long-term study.
All participants will be screened to confirm eligibility for participation. This involves providing biological samples (e.g., blood and urine) and undergoing additional physical procedures at study visits. Participants will have two muscle biopsies over the course of the study. Muscle biopsies are important because they allow researchers to compare whether there have been changes in the muscle as a result of the study drug. The study requires regular health check visits, which will be completed according to a schedule. During these visits, various tests will be conducted, including physical exams, heart rate, temperature, blood pressure, electrocardiogram, echocardiogram, and muscle function tests.
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-601-45 for participants is dystrophin production may increase and improve muscle function, but there is no guarantee this will happen. This is the first study of ENTR-601-45 in humans; therefore, there is no previous information on possible benefit in humans.
Similarly, this is the first study with the medication in humans, there is no previous information on side effects in humans. There have been studies done in laboratories on animals, 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?
December 2024 to March 2029
Who is funding the study?
The Sponsor, Entrada Therapeutics, Inc., is providing financial support and materials for this study. The study site is being paid by the Sponsor to do this study. Otherwise, the site staff including the study doctor have no financial ties to the Sponsor.
Who is the main contact?
clinicaltrials@entradatx.com
Contact information
Scientific
Wallace House
17-21 Maxwell Place
Stirling
FK8 1JU
United Kingdom
| UK-regulatory@medpace.com |
Principal Investigator
30 Guilford Street
London
WC1N 1EH
United Kingdom
| g.baranello@ucl.ac.uk |
Public, Scientific
1 Design Center Place
Suite 17-500
Boston
02210-2349
United States of America
| clinicaltrials@entradatx.com |
Study information
| Study design | Interventional double-blind randomized parallel group placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A 2-part, randomized, double-blind, placebo-controlled study in participants with Duchenne muscular dystrophy amenable to exon 45 skipping with an initial multiple ascending dose part A to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of ENTR-601-45, followed by part B to evaluate the safety and efficacy of ENTR-601-45 (ELEVATE-45) |
| Study acronym | ELEVATE-45 |
| Study objectives | Key Objectives (Part A): 1. To evaluate the safety and tolerability of ENTR-601-45 in participants with Duchenne muscular dystrophy (DMD) 2. To characterize the pharmacokinetics of ENTR-601-45 in participants with DMD 3. To characterize the pharmacodynamics of ENTR-601-45 in participants with DMD 4. To evaluate the immune response to ENTR-601-45 in participants with DMD |
| Ethics approval(s) | Approved 19/03/2025, London – Brent Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, UK; Tel: N/A; brent.rec@hra.nhs.uk), ref: 25/LO/0074 |
| Health condition(s) or problem(s) studied | Duchenne muscular dystrophy |
| Intervention | Experimental: ENTR-601-45. Participants will receive a fixed number of doses at one of three dose levels. One dose will be given every 6 weeks. Drug: ENTR601-45. Given by IV infusion as specified under Participant Group/Arm. Placebo Comparator Arm: ENTR-601-45 matching placebo Participants will receive a fixed number of placebo doses matched to ENTR-601-45 doses. One dose will be given every 6 weeks. Drug: ENTR-601-45 – Matching Placebo: Given by IV infusion as specified under Participant Group/Arm. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic, Dose response, Therapy |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | ENTR-601-45 |
| Primary outcome measure | 1. Overall safety and tolerability of ENTR-601-45, measured using: 1.1. Incidence and severity of treatment-emergent adverse events (TEAEs) 1.2. Changes in vital sign measurements 1.3. Clinical laboratory results 1.4. Electrocardiogram (ECG) parameters 1.5. Physical examination findings From baseline through the End of Study visit |
| Secondary outcome measures | 1. Plasma, muscle, and urine concentration of ENTR-601-45 and its final metabolite at prespecified timepoints during the study 2. Change from baseline in dystrophin by Western blot from muscle biopsy at the End of Study 3. Change from baseline in dystrophin expression and localization from muscle biopsy at the End of Study 4. Percent change from baseline in exon 45 skipping measured in muscle biopsy at the End of Study 5. Anti-drug antibody (ADA) and anti-dystrophin antibody in serum at prespecified timepoints during the study |
| Overall study start date | 23/12/2024 |
| Completion date | 01/03/2029 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 4 Years |
| Upper age limit | 20 Years |
| Sex | Male |
| Target number of participants | 24 |
| Key inclusion criteria | 1. Genetic diagnosis of DMD and confirmed pathologic variant in the dystrophin gene amenable to exon 45 skipping as reviewed by a central genetic counselor 2. Assigned male at birth with clinical signs compatible with Duchenne muscular dystrophy as determined by the investigator 3. Part A: 4-20 years of age, inclusive 4. Ambulatory Status Part A: ambulatory with a Performance of the Upper Limb v2.0 (PUL 2.0) Entry as per protocol at Screening 5. Adequate muscle for obtaining tissue biopsy as assessed by the investigator 6. Other protocol-defined criteria apply |
| Key exclusion criteria | 1. Any significant concomitant medical condition that might interfere with the ability to comply with protocol requirements. 2. Has an acute illness within 4 weeks prior to the first dose of study drug which may interfere with study measurements or jeopardize the participant’s safety 3. Use of the following medications: 3.1. Prior treatment with any exon skipping therapy at any time 3.2. Prior or current treatment with any gene therapy at any time 3.3. Use of anti-coagulants, anti-thrombotics, or anti-platelet agents 3.4. Use of an immunosuppressant for a non-DMD condition from 30 days prior to screening until the end of the study 3.5. Has taken or is currently taking a histone deacetylase (HDAC) inhibitor, including (but not limited to) givinostat from at least 30 days prior to the start of the screening period until the end of the study 4. Laboratory abnormalities 5. Daytime ventilator dependence or any use of invasive mechanical ventilation via tracheostomy 6. Has an abnormal electrocardiogram (ECG) reading assessed as clinically significant by the investigator, and/or a QT interval with Fridericia correction method (QTcF) >450 msec at Screening or prior to the first dose of study drug on Day 1 7. Received any experimental or investigational drug, etc within 3 months prior to first dose or within 5 half-lives (whichever is longer) 8. Other protocol-defined criteria apply |
| Date of first enrolment | 30/09/2025 |
| Date of final enrolment | 03/08/2028 |
Locations
Countries of recruitment
- Belgium
- England
- Italy
- Netherlands
- Spain
- United Kingdom
Study participating centres
Belgium
Belgium
Belgium
Italy
Italy
Italy
Spain
Spain
Netherlands
Netherlands
London
WC1N 3JH
United Kingdom
Eaton Road
West Derby
Liverpool
L12 2AP
United Kingdom
Leeds
LS1 3EX
United Kingdom
Pendlebury
Swinton
Manchester
M27 4HA
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Sponsor information
Industry
1 Design Center Place
Suite 17-500
Boston
02210-2349
United States of America
| clinicaltrials@entradatx.com |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Entrada Therapeutics, Inc.
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/10/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | 1. Peer-reviewed scientific journals 2. Internal report 3. Conference presentation 4. Publication on website 5. Other publication 6. Submission to regulatory authorities Study data will be posted as per local regulatory requirements, and all participant data will be pseudonymised through the use of a code (this is known as the participation identification number). Following completion of the study, the data may be considered for publication in a scientific journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data pertaining to the study confidential. The Investigator must consult with the Sponsor and obtain approval before any study data is submitted for publication. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to due to the data’s high commercial sensitivity. |
Editorial Notes
01/07/2025: Internal review.
20/03/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 20/03/2025.
30/12/2024: Study's existence confirmed by Health Research Authority (HRA) (UK)
