A follow-on study for second-eye treatment for participants previously treated with gene therapy for X-Linked Retinitis Pigmentosa (XLRP)
| ISRCTN | ISRCTN57691385 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN57691385 |
| IRAS number | 1010255 |
| ClinicalTrials.gov number | NCT06646289 |
| Secondary identifying numbers | 74765340RPG2001, CPMS 62454 |
- Submission date
- 06/08/2024
- Registration date
- 13/05/2025
- Last edited
- 01/07/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Eye Diseases
Plain English summary of protocol
Background and study aims
X-linked retinitis pigmentosa (XLRP) is an inherited eye condition that causes severe eye problems, eventually leading to blindness. It is commonly caused due to an alteration in a gene* called retinitis pigmentosa guanosine triphosphatase regulator (RPGR). Currently, there are no approved treatments available for XLRP.
*A part of DNA that contains the information for making a specific protein.
The study drug, AAV5-hRKp.RPGR, is a modified gene delivery system that carries a healthy version of the RPGR gene into the cells of an eye. This gene may help to improve and preserve vision. In this study, researchers want to learn how safe and tolerable it is to deliver AAV5-hRKp.RPGR under the retina into the second eye of a person who has already received it in their first eye.
Who can participate?
Male participants aged 5 years & older, previously treated with AAV5-hRKp.RPGR in one eye in the study MGT009 and have completed or are currently enrolled in Study MGT010.
What does the study involve?
Participants will be divided into 3 cohorts:
• Participants who are eligible to receive AAV5-hRKp.RPGR in the second eye through surgery will be enrolled sequentially (one after the other) into 2 cohorts:
o Cohort 1: After receiving treatment, participants will be assessed for safety through Week 12.
o Cohort 2: Participants will receive the treatment once safety is determined in Cohort 1.
o Cohort 3: Participants who do not wish to undergo surgery or are not eligible for surgery.
Study consists of:
1. Screening/Baseline period (up to 6 months)
2. Administration of AAV5-hRKp.RPGR under the retina (Day 1): Participants may receive a dose depending on the dosage administered in study MGT009 in the past.
3. Assessment period (52 weeks): Participants will undergo study assessments & tests including blood tests, imaging scans, eye examinations, efficacy outcome assessments & monitoring of side effects.
4. Long-term follow-up (4 years): The overall duration of the study will be approximately 5 years and 6 months.
What are the possible benefits and risks of participating?
There is no established benefit to participants of this study. Based on scientific theory, taking AAV5-hRKp.RPGR may improve eyesight. However, this cannot be guaranteed because AAV5-hRKp.RPGR is still under investigation as a treatment, and it is not known whether AAV5-hRKp.RPGR will work.
Participants may experience some benefit from participation in the study that is not due to receiving study drug, but due to regular visits and assessments monitoring overall health. Participation may help other people with X-linked Retinitis Pigmentosa in the future.
Participants may have side effects from the drugs or procedures used in this study that may be mild to severe and even life-threatening, and they can vary from person to person. Risks associated with standard surgical procedure itself, subretinal injection; those associated with gene therapy with a recombinant viral vector; adverse effects of corticosteroid prophylaxis (treatment given to prevent rejection of gene therapy) for immune suppression; and risks associated with study assessments. There are other, less frequent risks, like risks associated with the delivery of a recombinant viral vector. The participant information sheet and informed consent form, which will be signed by every participant agreeing to participate in the study, includes a detailed section outlining the known risks to participating in the study.
Not all possible side effects and risks related to AAV5-hRKp.RPGR are known at this moment. During the study, the sponsor may learn new information about AAV5-hRKp.RPGR. The study doctor will tell participants as soon as possible about any new information that might make them change their mind about being in the study, such as new risks.
To minimise the risk associated with taking part in the study, participants are frequently reviewed for any side effects and other medical events. Participants are educated to report any such events to their study doctor who will provide appropriate medical care. Any serious side effects that are reported to the sponsor are thoroughly reviewed by a specialist drug safety team.
There are no costs to participants to be in the study. The sponsor will pay for the study drug and tests that are part of the study. The participant will receive reasonable reimbursement for study related costs (e.g., travel/parking costs).
Where is the study run from?
Janssen-Cilag International NV (Netherlands)
When is the study starting and how long is it expected to run for?
August 2024 to October 2030
Who is funding the study?
Janssen Research & Development, LLC
Who is the main contact?
Lauren Ryan, lryan11@its.jnj.com
Prof. James Bainbridge, james.bainbridge1@nhs.net
Contact information
Public, Scientific
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
| Phone | 44 7920 813 470 |
|---|---|
| lryan11@its.jnj.com |
Principal Investigator
162 City Road
London
EC1V 2PD
United Kingdom
| Phone | +44 207 566 2059 |
|---|---|
| james.bainbridge1@nhs.net |
Study information
| Study design | Interventional non randomized |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Scientific title | An open-label, multicenter, phase 2 follow-on study for second eye treatment of patients previously treated with a recombinant Adeno-associated Virus Vector (AAV5 hRKp.RPGR) for gene therapy of adults and children with x-linked retinitis pigmentosa owing to defects in Retinitis Pigmentosa GTPase Regulator (RPGR) |
| Study acronym | RPG2001 |
| Study objectives | Primary objective: To assess how safe and tolerable it is to deliver AAV5- hRKp.RPGR under the retina (back part of eye that senses light) into a single eye. Secondary objectives: To assess whether AAV5-hRKp.RPGR improves the vision-related activities and to assess the following changes after taking treatment with AAV5- hRKp.RPGR: 1. How well the retina works (retinal function) 2. How well a person can use eyesight in daily life (functional vision) 3. How well a person can see (visual function) |
| Ethics approval(s) |
Approved 01/10/2024, West London & GTAC Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 2071048075; westlondon.rec@hra.nhs.uk), ref: 24/LO/0470 |
| Health condition(s) or problem(s) studied | X-Linked Retinitis Pigmentosa |
| Intervention | Experimental: Cohort 1 Participants will receive a dose of AAV5 hRKp.RPGR under the retina (low-dose or intermediate-dose) on Day 1 depending on the dosage administered in study MGT009 (NCT03252847) in the past. After receiving the treatment, participants will be assessed for safety. Assigned interventions: Biological/Vaccine: AAV5-hRKp.RPGR. AAV5-hRKp.RPGR will be administered sub-retinally. Other Names:• JNJ-74765340, botaretigene sparoparvovec Experimental: Cohort 2 Participants will receive the treatment dose of AAV5 hRKp.RPGR under the retina (low-dose or intermediate-dose) on Day 1 in the second eye once the safety will be determined in Cohort 1. Assigned interventions: Biological/Vaccine: AAV5-hRKp.RPGR. AAV5-hRKp.RPGR will be administered sub-retinally. Other Names: JNJ-74765340, botaretigene sparoparvovec Cohort 3 The participants who are not willing to undergo surgery or are not eligible for surgery will be assessed in this cohort. They will be assessed yearly until 5 years after their initial eye surgery in previous study MGT009. No intervention (Follow-Up assessment). Participants will not receive any intervention and will undergo follow-up assessment. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Therapy, Others (Immunogenicity and biodistribution/shedding.) |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | AAV5-hRKp.RPGR |
| Primary outcome measure | 1. Number of Participants With Adverse Events (AE): From baseline up to 5.5 years |
| Secondary outcome measures | 1. Change from Baseline in Mean Retinal Sensitivity Within the Central 10 Degrees (MRS10) to Months 12, 24, 36, 48 and 60 2. Change in Retinal Function as Assessed by Pointwise Response in Static Perimetry. From Month 12 up to Month 60 3. Change in Retinal Function as Assessed by Pointwise Response in Static Perimetry Within Central 30 Degrees Visual Field. From Month 12 up to Month 60 4. Change from Baseline in Mean Retinal Sensitivity Within the Full Visual Field (MRS90) to Months 12, 24, 36, 48 and 60 5. Change from Baseline in the Low Luminance Questionnaire (LLQ) Domain Scores to Month 12 6. Change from Baseline in Low Luminance Visual Acuity (LLVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart Letter Score to Months 12, 24, 36, 48 and 60 7. Change from Baseline in Best Corrected Visual Acuity (BCVA) by ETDRS Chart Letter Scores to Months 12, 24, 36, 48 and 60 |
| Overall study start date | 02/08/2024 |
| Completion date | 24/10/2030 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Male |
| Target number of participants | 29 |
| Key inclusion criteria | 1. Have been treated with AAV5-hRKp.RPGR in study MGT009 and have completed or is currently enrolled in Study MGT010- 2. Must sign an informed consent form indicating that they understand the purpose and procedures of the study and is willing to participate in the study 3. Willing to adhere to the protocol and long-term follow-up |
| Key exclusion criteria | There are no specific exclusion criteria to enroll in this study |
| Date of first enrolment | 25/04/2025 |
| Date of final enrolment | 31/10/2025 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
Industry
Archimedesweg 29
Leiden
2333CM
Netherlands
| Phone | +31 715242166 |
|---|---|
| ClinicalTrialsEU@its.jnj.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 24/10/2031 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Submission to regulatory authorities Other Study results may be available via publication in scientific journals & presentation at scientific meetings. Results will be made available to participants via a Plain Language Summary a year after the end of the study. The summary will describe the results regardless of study outcome in language that is understandable to the general public. It will not contain individual participant results or their personal information. A copy of the Summary will be provided to the REC. |
| IPD sharing plan | The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu |
Editorial Notes
01/07/2025: Internal review.
02/10/2024: ISRCTN received notification of combined HRA/MHRA approval for this trial on 02/10/2024
06/08/2024: Trial's existence confirmed by NHS HRA.
