X-Linked Retinitis PigmentosaPhase 1/2NCT03252847
Gene Therapy for X-linked Retinitis Pigmentosa (XLRP) - Retinitis Pigmentosa GTPase Regulator (RPGR)
A Phase 1/2 study testing AAV5-RPGR in people with X-Linked Retinitis Pigmentosa, run by MeiraGTx UK II Ltd at 5 sites in 2 countries.
Trial summary
Phase 1 of the study is a dose escalation of the subretinal administration of AAV5-hRKp.RPGR vector to assess the safety of this vector in participants with XLRP caused by mutations in RPGR. Participants enrolled in Phase 1 were assigned to a dose group based on when they enrolled (i.e., sequential assignment). Read more about this study
- Who is it for?
- Ages 5 years and older, men only
- Conditions the study is for
- X-Linked Retinitis Pigmentosa
- What is being tested?
- AAV5-RPGR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 31 Jul 2017to 18 Nov 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Males aged 5 years or older
- Have X-linked retinitis pigmentosa confirmed by a retinal specialist (CI or PI)
Who cannot join
- Have participated in another research study involving an investigational medicinal therapy for ocular disease within the last 6 months
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States3 sites
Kellogg Eye Center
Ann Arbor, Michigan, 48105
Massachusetts Eye and Ear Institute
Boston, Massachusetts, 02114
UPMC Eye Center
Pittsburgh, Pennsylvania, 15213
United Kingdom2 sites
Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF
Moorfields Eye Hospital NHS Foundation Trust
London
About this study
Official title: An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/5-hRKp.RPGR) for Gene Therapy of Adults and Children With X-linked Retinitis Pigmentosa Owing to Defects in Retinitis Pigmentosa GTPase Regulator (RPGR)
Phase 1 of the study is a dose escalation of the subretinal administration of AAV5-hRKp.RPGR vector to assess the safety of this vector in participants with XLRP caused by mutations in RPGR. Participants enrolled in Phase 1 were assigned to a dose group based on when they enrolled (i.e., sequential assignment).
Phase 2 of the study is a cohort expansion of the subretinal administration of AAV5-hRKp.RPGR vector to assess the safety and efficacy of this vector in participants with XLRP caused by mutations in RPGR. Participants enrolled in Phase 2 were randomized to immediate or deferred treatment.
Read the detailed description
This is an open-label phase 1/2 dose-escalation and cohort expansion trial to determine the safety and efficacy of subretinal administration of AAV5-hRKp.RPGR vector in participants with XLRP caused by mutations in RPGR.
- Conditions
- X-Linked Retinitis Pigmentosa
- Being tested
- AAV5-RPGR
- Keywords
- XLRP RPGR
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV5-RPGRGenetic
Single, subretinal administration of AAV5-RPGR
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 (Part 1, Dose Escalation) | Experimental | Participants receive one of three doses of AAV5-RPGR Receives: Genetic: AAV5-RPGR |
| Phase 2 (Part 2; Expansion) | Experimental | Participants receive one of two doses of AAV5-RPGR Receives: Genetic: AAV5-RPGR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Meeting the Primary Outcome Defined as Any of the Below Events Occurring During the 9 Weeks Following Administration, at Least Possibly Related to the Advanced Therapy Investigational Medicinal Product (ATIMP), Not Surgery Alone.
The primary outcome is defined as any of the below occurring during the 9 weeks following administration, at least possibly related to the Advanced Therapy Investigational Medicinal Product (ATIMP), not surgery alone:
- Reduction in visual acuity by 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more
- Severe unresponsive inflammation
- Infective endophthalmitis
- Ocular malignancy
- Grade III or above non-ocular Suspected Unexpected Serious Adverse Reaction (SUSAR)
Measured: 9 weeks
Secondary outcomes (7)
Improvements in Visual Function as Assessed by Visual Acuity
Change from baseline to Week 26 in best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score. The direction of improvement from baseline is an increase in the number of ETDRS letters read over time.
Measured: Baseline and Month 6
Improvements in Retinal Function as Assessed by Static Perimetry
The number of responders in point-by-point data in Static Perimetry within the full visual field over time.
A responder at a single time point is defined as a participant with at least 5 of the same loci with ≥7 dB improvement from baseline at the specific time point and one time point prior.
Measured: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Emotional Distress Domain Score
Change from baseline to Week 26 in LLQ Emotional Distress Domain Score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Measured: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Extreme Lighting Domain Score
Change from baseline to Week 26 in LLQ Extreme Lighting Domain Score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Measured: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) General Dim Lighting Domain Score
Change from baseline to Week 26 in LLQ General Dim Lighting Domain score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Measured: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Mobility Domain Score
Change from baseline to Week 26 in LLQ Mobility Domain Score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Measured: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Peripheral Vision Domain Score
Change from baseline to Week 26 in LLQ Peripheral Vision Domain Score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Measured: Baseline and Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2017
- Study start31 Jul 2017
- Primary completion18 Nov 2021
- Study completion18 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for X-Linked Retinitis PigmentosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Biological
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- MeiraGTx UK II Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Syne Qua Non Limited, Bionical Emas
- Responsible party
- Sponsor
- Investigators
- James Bainbridge, Prof, Principal investigator, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03252847
- Sponsor's protocol ID
- MGT009
- Status last verified
- Dec 2024
- First submitted
- 1 Aug 2017
- Last updated
- 8 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Michaelides M, Besirli CG, Yang Y, DE Guimaraes TAC, Wong SC, Huckfeldt RM, Comander JI, Sahel JA, Shah SM, Tee JJL, Kumaran N, Georgiadis A, Minnick P, Zeldin R, Naylor S, Xu J, Clark M, Anglade E, Wong P, Fleck PR, Fung A, Peluso C, Kalitzeos A, Georgiou M, Ripamonti C, Smith AJ, Ali RR, Forbes A, Bainbridge J. Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-Associated X-Linked Retinitis Pigmentosa. Am J Ophthalmol. 2024 Nov;267:122-134. doi: 10.1016/j.ajo.2024.05.034. Epub 2024 Jun 12.
PubMed 38871269
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/5-hRKp.RPGR) for Gene Therapy of Adults and Children With X-linked Retinitis Pigmentosa Owing to Defects in Retinitis Pigmentosa GTPase Regulator (RPGR)
- ClinicalTrials.gov ID
- NCT03252847
- Acronym / sponsor ID
- MGT009
- Conditions
- X-Linked Retinitis Pigmentosa
- Keywords
- XLRP RPGR
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- MeiraGTx UK II LtdIndustry (pharma, biotech, devices)
- Collaborators
- Syne Qua Non Limited, Bionical Emas
- Study start
- 31 Jul 2017 (actual)
- Primary completion
- 18 Nov 2021 (actual)
- Study completion
- 18 Nov 2021 (actual)
- First posted
- 17 Aug 2017 (actual)
- Results
- Posted 8 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1 of the study is a dose escalation of the subretinal administration of AAV5-hRKp.RPGR vector to assess the safety of this vector in participants with XLRP caused by mutations in RPGR. Participants enrolled in Phase 1 were assigned to a dose group based on when they enrolled (i.e., sequential assignment).
Phase 2 of the study is a cohort expansion of the subretinal administration of AAV5-hRKp.RPGR vector to assess the safety and efficacy of this vector in participants with XLRP caused by mutations in RPGR. Participants enrolled in Phase 2 were randomized to immediate or deferred treatment.
Detailed description
This is an open-label phase 1/2 dose-escalation and cohort expansion trial to determine the safety and efficacy of subretinal administration of AAV5-hRKp.RPGR vector in participants with XLRP caused by mutations in RPGR.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Biological
| Arm | Type | Receives |
|---|---|---|
| Phase 1 (Part 1, Dose Escalation) | Experimental | Genetic: AAV5-RPGRParticipants receive one of three doses of AAV5-RPGR |
| Phase 2 (Part 2; Expansion) | Experimental | Genetic: AAV5-RPGRParticipants receive one of two doses of AAV5-RPGR |
Who may qualify
- Ages
- 5 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Males aged 5 years or older
- Have X-linked retinitis pigmentosa confirmed by a retinal specialist (CI or PI)
Key exclusion criteria (1 listed)
- Have participated in another research study involving an investigational medicinal therapy for ocular disease within the last 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAV5-RPGRSingle, subretinal administration of AAV5-RPGR | Genetic | Phase 1 (Part 1, Dose Escalation), Phase 2 (Part 2; Expansion) |
Primary outcome
Number of Participants Meeting the Primary Outcome Defined as Any of the Below Events Occurring During the 9 Weeks Following Administration, at Least Possibly Related to the Advanced Therapy Investigational Medicinal Product (ATIMP), Not Surgery Alone.
Time frame: 9 weeks
The primary outcome is defined as any of the below occurring during the 9 weeks following administration, at least possibly related to the Advanced Therapy Investigational Medicinal Product (ATIMP), not surgery alone: * Reduction in visual acuity by 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more * Severe unresponsive inflammation * Infective endophthalmitis * Ocular malignancy * Grade III or above non-ocular Suspected Unexpected Serious Adverse Reaction (SUSAR)
7 secondary outcomes
Improvements in Visual Function as Assessed by Visual Acuity
Time frame: Baseline and Month 6
Improvements in Retinal Function as Assessed by Static Perimetry
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Emotional Distress Domain Score
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Extreme Lighting Domain Score
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) General Dim Lighting Domain Score
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Mobility Domain Score
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Peripheral Vision Domain Score
Time frame: Baseline and Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38871269Michaelides M, Besirli CG, Yang Y, DE Guimaraes TAC, Wong SC, Huckfeldt RM, Comander JI, Sahel JA, Shah SM, Tee JJL, Kumaran N, Georgiadis A, Minnick P, Zeldin R, Naylor S, Xu J, Clark M, Anglade E, Wong P, Fleck PR, Fung A, Peluso C, Kalitzeos A, Georgiou M, Ripamonti C, Smith AJ, Ali RR, Forbes A, Bainbridge J. Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-Associated X-Linked Retinitis Pigmentosa. Am J Ophthalmol. 2024 Nov;267:122-134. doi: 10.1016/j.ajo.2024.05.034. Epub 2024 Jun 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Bainbridge, Prof principal investigator
University College, London
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AAV5-RPGR in people with X-Linked Retinitis Pigmentosa, run by MeiraGTx UK II Ltd at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Meeting the Primary Outcome Defined as Any of the Below Events Occurring During the 9 Weeks Following Administration, at Least Possibly Related to the Advanced Therapy Investigational Medicinal Product (ATIMP), Not Surgery Alone. (time frame: 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03252847, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2025.