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CompletedNCT03252847Updated Jan 8, 2025Results posted

Gene Therapy for X-linked Retinitis Pigmentosa (XLRP) - Retinitis Pigmentosa GTPase Regulator (RPGR)

A Phase 1/2 interventional study of AAV5-RPGR in X-Linked Retinitis Pigmentosa, sponsored by MeiraGTx UK II Ltd. Completed at 5 sites in 2 countries. Open to male participants aged 5 Years and older. Per ClinicalTrials.gov, last updated 2025-01-08.

Sponsored by MeiraGTx UK II Ltd · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
49
Allocation
Randomized
Ages
5 Years and older
Sex
Male
01

Study 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).

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.

02

Conditions studied

  • X-Linked Retinitis Pigmentosa

Keywords

  • XLRP RPGR
03

Who can participate

Ages eligible
5 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Eligibility criteria

Key inclusion Criteria:

  • Males aged 5 years or older
  • Have X-linked retinitis pigmentosa confirmed by a retinal specialist (CI or PI)

Key exclusion Criteria:

  • Have participated in another research study involving an investigational medicinal therapy for ocular disease within the last 6 months
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
49 participants (actual)

Study arms

  • Experimental
    Phase 1 (Part 1, Dose Escalation)

    Participants receive one of three doses of AAV5-RPGR

    Genetic: AAV5-RPGR

  • Experimental
    Phase 2 (Part 2; Expansion)

    Participants receive one of two doses of AAV5-RPGR

    Genetic: AAV5-RPGR

Interventions

  • GeneticAAV5-RPGR

    Single, subretinal administration of AAV5-RPGR

05

What researchers measure

Primary outcomes

  1. 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)

    Time frame: 9 weeks

Secondary outcomes

  1. 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.

    Time frame: Baseline and Month 6

  2. 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.

    Time frame: Baseline and Month 6

  3. 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.

    Time frame: Baseline and Month 6

  4. 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.

    Time frame: Baseline and Month 6

  5. 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.

    Time frame: Baseline and Month 6

  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.

    Time frame: Baseline and Month 6

  7. 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.

    Time frame: Baseline and Month 6

06

Results

Posted Jan 8, 2025

Participant flow

Participants were recruited from 5 sites (2 in the UK and 3 in the US) between 31 Jul 2017 and 18 Nov 2021. 49 participants were enrolled in the study; 4 participants discontinued before receiving treatment. The study consisted of 2 phases: dose escalation (Phase 1) followed by dose expansion (Phase 2). In Phase 1, 13 participants enrolled in 1 of 3 treatment groups. In Phase 2, 36 participants were randomized to an active treatment arm or a control arm with treatment deferred for 6 months.

Participant flow — Overall Study
MilestonePhase 1: Immediate Low Dose AAV5-hRKp.RPGRPhase 1: Immediate Intermediate Dose AAV5-hRKp.RPGRPhase 1: Immediate High Dose AAV5-hRKp.RPGRPhase 2: Immediate Low Dose AAV5-hRKp.RPGRPhase 2: Immediate Intermediate Dose AAV5-hRKp.RPGRPhase 2: Immediate High Dose AAV5-hRKp.RPGRPhase 2: Deferred Group
Started373810113
Completed37289113
Not completed0010100
Withdrew: Withdrawal by subject0010000
Withdrew: Other: patient decision0000100

Outcome measures

PrimaryNumber 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)

Time frame:
9 weeks
Reported as:
Count of participants · Participants
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.
ParticipantsImmediate Low Dose AAV5-hRKp.RPGRImmediate Intermediate Dose AAV5-hRKp.RPGRImmediate High Dose AAV5-hRKp.RPGRDeferred Group
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.0000
SecondaryImprovements 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.

Time frame:
Baseline and Month 6
Reported as:
Mean · Number of EDTRS letters
Improvements in Visual Function as Assessed by Visual Acuity
Number of EDTRS lettersImmediate Treatment Group AAV5-hRKp.RPGRDeferred Group
Improvements in Visual Function as Assessed by Visual Acuity0.6 ± 4.74-3.2 ± 3.87
SecondaryImprovements 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.

Time frame:
Baseline and Month 6
Reported as:
Count of participants · Participants
Improvements in Retinal Function as Assessed by Static Perimetry
ParticipantsImmediate Treatment Group AAV5-hRKp.RPGRDeferred Group
Improvements in Retinal Function as Assessed by Static Perimetry62
SecondaryQuality 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.

Time frame:
Baseline and Month 6
Reported as:
Mean · Units on a scale
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Emotional Distress Domain Score
Units on a scaleImmediate Treatment Group AAV5-hRKp.RPGRDeferred Group
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Emotional Distress Domain Score2.344 ± 20.1395-1.389 ± 8.7152
SecondaryQuality 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.

Time frame:
Baseline and Month 6
Reported as:
Mean · Units on a scale
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Extreme Lighting Domain Score
Units on a scaleImmediate Treatment Group AAV5-hRKp.RPGRDeferred Group
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Extreme Lighting Domain Score2.956 ± 9.7080-8.059 ± 5.8453
SecondaryQuality 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.

Time frame:
Baseline and Month 6
Reported as:
Mean · Units on a scale
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) General Dim Lighting Domain Score
Units on a scaleImmediate Treatment Group AAV5-hRKp.RPGRDeferred Group
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) General Dim Lighting Domain Score4.115 ± 14.97061.852 ± 11.8056
SecondaryQuality 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.

Time frame:
Baseline and Month 6
Reported as:
Mean · Units on a scale
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Mobility Domain Score
Units on a scaleImmediate Treatment Group AAV5-hRKp.RPGRDeferred Group
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Mobility Domain Score5.729 ± 15.87530.926 ± 6.5145
SecondaryQuality 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.

Time frame:
Baseline and Month 6
Reported as:
Mean · Units on a scale
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Peripheral Vision Domain Score
Units on a scaleImmediate Treatment Group AAV5-hRKp.RPGRDeferred Group
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Peripheral Vision Domain Score1.563 ± 18.8116-1.852 ± 9.1076

Adverse events

Collected over Data are included from the signing of the ICF until the Month 12 visit.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Immediate Low Dose AAV5-hRKp.RPGR0/11 (0%)2/11 (18.2%)11/11 (100%)
Immediate Intermediate Dose AAV5-hRKp.RPGR0/17 (0%)0/17 (0%)17/17 (100%)
Immediate High Dose AAV5-hRKp.RPGR0/4 (0%)0/4 (0%)4/4 (100%)
Deferred Group - Before Treatment (Control Group)0/13 (0%)0/13 (0%)1/13 (7.7%)
Deferred Group - Low Dose AAV5-hRKp.RPGR - After Treatment0/7 (0%)1/7 (14.3%)7/7 (100%)
Deferred Group - Intermediate Dose AAV5-hRKp.RPGR - After Treatment0/6 (0%)0/6 (0%)6/6 (100%)
Most frequent serious events
Most frequent serious events
EventImmediate Low Dose AAV5-hRKp.RPGRImmediate Intermediate Dose AAV5-hRKp.RPGRImmediate High Dose AAV5-hRKp.RPGRDeferred Group - Before Treatment (Control Group)Deferred Group - Low Dose AAV5-hRKp.RPGR - After TreatmentDeferred Group - Intermediate Dose AAV5-hRKp.RPGR - After Treatment
Intraocular pressure increasedInvestigations0/110/170/40/131/70/6
Retinal DetachmentEye disorders1/110/170/40/130/70/6
UveitisEye disorders1/110/170/40/130/70/6
Most frequent other events
Showing 10 of 26
Most frequent other events
EventImmediate Low Dose AAV5-hRKp.RPGRImmediate Intermediate Dose AAV5-hRKp.RPGRImmediate High Dose AAV5-hRKp.RPGRDeferred Group - Before Treatment (Control Group)Deferred Group - Low Dose AAV5-hRKp.RPGR - After TreatmentDeferred Group - Intermediate Dose AAV5-hRKp.RPGR - After Treatment
Conjunctival haemorrhageEye disorders8/1111/174/40/132/73/6
Visual acuity reducedEye disorders6/118/172/40/136/76/6
Anterior chamber cellEye disorders4/119/173/40/132/72/6
Intraocular pressure increasedInvestigations5/119/172/40/134/72/6
Foreign body sensation in eyesEye disorders1/115/172/40/130/70/6
UveitisEye disorders0/112/172/40/130/70/6
RhinitisInfections and infestations2/112/172/40/131/70/6
Conjunctival hyperaemiaEye disorders2/112/170/40/133/70/6
Eye inflammationEye disorders3/115/170/40/132/71/6
Intraocular pressure decreasedInvestigations2/111/170/40/132/70/6

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Immediate Low Dose AAV5-hRKp.RPGRImmediate Intermediate Dose AAV5-hRKp.RPGRImmediate High Dose AAV5-hRKp.RPGRDeferred GroupTotal
<=18 years03003
Between 18 and 65 years111441342
>=65 years00000
Sex: Female, Male
Sex: Female, Male(Participants)Immediate Low Dose AAV5-hRKp.RPGRImmediate Intermediate Dose AAV5-hRKp.RPGRImmediate High Dose AAV5-hRKp.RPGRDeferred GroupTotal
Female00000
Male111741345
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Immediate Low Dose AAV5-hRKp.RPGRImmediate Intermediate Dose AAV5-hRKp.RPGRImmediate High Dose AAV5-hRKp.RPGRDeferred GroupTotal
Hispanic or Latino01023
Not Hispanic or Latino111641142
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Immediate Low Dose AAV5-hRKp.RPGRImmediate Intermediate Dose AAV5-hRKp.RPGRImmediate High Dose AAV5-hRKp.RPGRDeferred GroupTotal
American Indian or Alaska Native00000
Asian00000
Native Hawaiian or Other Pacific Islander00000
Black or African American00101
White101531341
More than one race00000
Unknown or Not Reported12003
Region of Enrollment
Region of Enrollment(participants)Immediate Low Dose AAV5-hRKp.RPGRImmediate Intermediate Dose AAV5-hRKp.RPGRImmediate High Dose AAV5-hRKp.RPGRDeferred GroupTotal
United States351514
United Kingdom8123831
07

Study locations

5 sites
  • Massachusetts Eye and Ear Institute
    Boston, Massachusetts 02114, United States
  • Kellogg Eye Center
    Ann Arbor, Michigan 48105, United States
  • UPMC Eye Center
    Pittsburgh, Pennsylvania 15213, United States
  • Leeds Teaching Hospitals NHS Trust
    Leeds, LS9 7TF, United Kingdom
  • Moorfields Eye Hospital NHS Foundation Trust
    London, United Kingdom
08

References and documents

Study documents

  • Study protocol · May 1, 2020
  • Statistical analysis plan · Nov 16, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03252847
Lead sponsor
MeiraGTx UK II Ltd
Collaborators
Syne Qua Non Limited, Bionical Emas
Responsible party
Sponsor
First posted
Aug 17, 2017
Start date
Jul 31, 2017
Primary completion
Nov 18, 2021
Completion
Nov 18, 2021
Results posted
Jan 8, 2025
Last update
Jan 8, 2025

Study contacts

James Bainbridge, Prof
principal investigator · University College, London

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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