Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene

• ClinicalTrials.gov Identifier: NCT04671433
• Recruitment Status: Active, not recruiting
• First Posted: December 17, 2020
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: November 5, 2020
• First Posted Date: December 17, 2020
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: December 4, 2020
• Estimated Primary Completion Date: September 20, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 23, 2024)

Change From Baseline to Week 52 in Vision-guided Mobility Assessment (VMA) as Measured by the Ability of the Participant to Navigate Through a VMA Maze [ Time Frame: From Baseline to 52 Weeks ]

Change from baseline to Week 52 in VMA as measured by the ability of the participant to navigate through a VMA maze.

• Original Primary Outcome Measures (submitted: December 15, 2020): Change from baseline in retinal sensitivity as measured by perimetry [ Time Frame: 52 Weeks ]

Current Secondary Outcome Measures (submitted: January 23, 2024)

• Change From Baseline in Mean Retinal Sensitivity Within the Central 10 Degrees Excluding Scotoma (Mean Retinal Sensitivity Within the Central 10 Degree Excluding Scotoma in Static Perimetry [MRS10]) in Static Perimetry at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Change from baseline in mean retinal sensitivity within the central 10 degrees excluding scotoma (MRS10) in static perimetry at Week 52 will be assessed.
• Change From Baseline in Mean Retinal Sensitivity of Worse-seeing Eye Within the Central 10 Degrees Excluding Scotoma in Static Perimetry (MRS10) at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Change from baseline in mean retinal sensitivity of worse-seeing eye within the central 10 degrees excluding scotoma in static perimetry (MRS10) at Week 52 will be assessed.
• Change in Retinal Function as Assessed by Pointwise Response in Full Visual Field at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Pointwise response in full visual field at Week 52 will be assessed.
• Change in Retinal Function as Assessed by Pointwise Response in Worse-seeing Eye in Full Visual Field at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Pointwise response in worse-seeing eye in full visual field at Week 52 will be assessed.
• Change in Retinal Function as Assessed by Pointwise Response in the Central 30 Degrees Visual Field at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Pointwise response in the central 30 degrees visual field at Week 52 will be assessed.
• Change in Retinal Function as Assessed by Pointwise Response in Worse-seeing Eye in the Central 30 Degrees Visual Field at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Pointwise response in worse-seeing eye in the central 30 degrees visual field at Week 52 will be assessed.
• Change From Baseline in Retinal Function as Assessed by Mean Retinal Sensitivity Within the Full Visual Field (MRS90) in Static Perimetry at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Change from baseline in retinal function as assessed by mean retinal sensitivity within the full visual field (MRS90) in static perimetry at Week 52 will be assessed.
• Change in Functional Vision by Using Vision-guided Mobility Assessment (VMA) Response in the "Worse-seeing Eye" at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Change in functional vision by using VMA assessment in the "Worse-seeing Eye" at Week 52.
• Change From Baseline in the Modified Low Luminance Questionnaire (mLLQ) Extreme Lighting Domain score at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Change From Baseline in the Modified Low Luminance Questionnaire (mLLQ) Extreme Lighting Domain score at Week 52.
• Change From Baseline in Visual Function as Assessed by Monocular Low Luminance Visual Acuity Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart Letter score at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Change from baseline in visual function as assessed by monocular low luminance visual acuity using the ETDRS chart letter score at Week 52.
• Change From Baseline in Visual Function as Assessed by monocular Best Corrected Visual Acuity (BCVA) Using the ETDRS Chart Letter Score at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Change From Baseline in visual function as assessed by monocular BCVA using the ETDRS chart letter score at Week 52.
• Change From Baseline in Visual Function as Assessed by Low Luminance Visual Acuity Using the ETDRS Chart Letter Score in Worse-seeing Eye at Week 52 [ Time Frame: From Baseline to Week 52 ]
  Change from baseline in visual function as assessed by low luminance visual acuity using the ETDRS chart letter score in worse-seeing eye at Week 52.
• Number of Participants with Ocular and Non-ocular Adverse Events [ Time Frame: Day 1 - Week 52 ]
  Number of participants with ocular and non-ocular adverse events will be assessed.
• Number of Participants With Abnormalities in Laboratory Assessments [ Time Frame: Day 1 - 52 Weeks ]
  Number of participants with abnormalities in laboratory assessments will be assessed.

Original Secondary Outcome Measures (submitted: December 15, 2020)

• Change from baseline in visual function as measured by ETDRS [ Time Frame: Day 0 - Week 52 ]
• To assess changes in functional vision: • Change from baseline in functional vision as measured by visual mobility assessment • Change from baseline in functional vision as measured by patient-reported outcomes [ Time Frame: Day 0 - Week 52 ]
• Change from baseline in visual function as measured by contrast sensitivity [ Time Frame: Day 0 - Week 52 ]
• Safety and tolerability of bilateral treatment with AAV5-RPGR as measured by: • Number of participants with ocular and non-ocular adverse events • Number of participants with abnormalities in Hematologic and Clinical Chemistry parameters [ Time Frame: Day 0 - Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene
• Official Title: Phase 3 Randomized, Controlled Study of AAV5-hRKp.RPGR for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene
• Brief Summary: A clinical trial of AAV5-RPGR vector for participants with X-linked retinitis pigmentosa (XLRP)
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Bilateral, subretinal administration of AAV5-RPGR - immediate treatment group

Masking: Single (Outcomes Assessor)
Masking Description:

No intervention - deferred treatment group (Bilateral, subretinal administration of AAV5-RPGR to be administered in the follow-up study)

Primary Purpose: Treatment

• Condition: X-Linked Retinitis Pigmentosa

Intervention

• Biological: Genetic: AAV5-hRKp.RPGR
  Bilateral, sub-retinal administration of AAV5-hRKp.RPGR - immediate treatment group
  Other Name: botaretigene sparoparvovec
• Biological: Genetic: AAV5-hRKp.RPGR
  No intervention - deferred treatment group (Bilateral, sub-retinal administration of AAV5-hRKp.RPGR to be administered in the follow-up study)

Study Arms

• Experimental: Experimental - Immediate Treatment
  Intermediate dose.
  Intervention: Biological: Genetic: AAV5-hRKp.RPGR
• Deferred Treatment
  Deferred Treatment
  Intervention: Biological: Genetic: AAV5-hRKp.RPGR
• Experimental: Experimental Immediate Treatment
  Low dose.
  Intervention: Biological: Genetic: AAV5-hRKp.RPGR

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 21, 2023): 97
• Original Estimated Enrollment (submitted: December 15, 2020): 48
• Estimated Study Completion Date: September 20, 2024
• Estimated Primary Completion Date: September 20, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female
• 3 years of age or older
• Has XLRP confirmed by a retinal specialist and has a predicted disease-causing sequence variant in RPGR confirmed by an accredited laboratory

Exclusion Criteria:

• Has had ocular surgery within 3 months prior to screening or is anticipated to require ocular surgery within 6 months after the study intervention administration
• Any investigational ocular treatment or any other ocular treatment that could confound the interpretation of the efficacy results or affect participant compliance with the visit schedule
• Has undergone prior retinal surgery involving the macula, macular laser photocoagulation, external-beam radiation therapy, transpupillary thermotherapy, glaucoma filtration surgery or corneal surgery

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Denmark, France, Israel, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT04671433
• Other Study ID Numbers: CR109258; MGT-RPGR-021 ( Other Identifier: Janssen Research & Development, LLC ); 2020-002873-88 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: MeiraGTx UK II Ltd
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: MeiraGTx UK II Ltd
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024