Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Syne Qua Non Limited | INDUSTRY |
| Bionical Emas | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1 (Part 1, Dose Escalation) | Experimental | Participants receive one of three doses of AAV5-RPGR |
|
| Phase 2 (Part 2; Expansion) | Experimental | Participants receive one of two doses of AAV5-RPGR |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AAV5-RPGR | Genetic | Single, subretinal administration of AAV5-RPGR |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| 9 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Month 6 |
Not provided
Key inclusion Criteria:
Key exclusion Criteria:
• Have participated in another research study involving an investigational medicinal therapy for ocular disease within the last 6 months
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| James Bainbridge, Prof | University College, London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts Eye and Ear Institute | Boston | Massachusetts | 02114 | United States | ||
| Kellogg Eye Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38871269 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1: Immediate Low Dose AAV5-hRKp.RPGR | Subretinal administration of a single low dose of AAV5-hRKp.RPGR in Phase 1 of the study. AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene. |
| FG001 | Phase 1: Immediate Intermediate Dose AAV5-hRKp.RPGR | Subretinal administration of a single intermediate dose of AAV5-hRKp.RPGR in Phase 1 of the study. AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene. |
| FG002 | Phase 1: Immediate High Dose AAV5-hRKp.RPGR | Subretinal administration of a single high dose of AAV5-hRKp.RPGR in Phase 1 of the study. AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene. |
| FG003 | Phase 2: Immediate Low Dose AAV5-hRKp.RPGR | Subretinal administration of a single low dose of AAV5-hRKp.RPGR in Phase 2 of the study. AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene. |
| FG004 | Phase 2: Immediate Intermediate Dose AAV5-hRKp.RPGR | Subretinal administration of a single intermediate dose of AAV5-hRKp.RPGR in Phase 2 of the study. AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene. |
| FG005 | Phase 2: Immediate High Dose AAV5-hRKp.RPGR | Subretinal administration of a single high dose of AAV5-hRKp.RPGR in Phase 2 of the study. AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene. |
| FG006 | Phase 2: Deferred Group | Treatment of participants in this Phase 2 study group was deferred for 6 months |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Immediate Low Dose AAV5-hRKp.RPGR | Subretinal administration of a single low dose of AAV5-hRKp.RPGR in either Phase 1 or Phase 2 of the study (prespecified pooling). AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene |
| BG001 | Immediate Intermediate Dose AAV5-hRKp.RPGR |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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:
| The primary endpoint was analyzed for participants in the dose escalation phase (i.e., study Phase 1) only | Posted | Count of Participants | Participants | 9 weeks |
|
Data are included from the signing of the ICF until the Month 12 visit.
There were 3 SAEs (all non-fatal) reported during the study: 2 in the immediate treatment group (preferred terms retinal detachment and uveitis) and 1 in the deferred treatment group after surgery (preferred term intraocular pressure increased).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Immediate Low Dose AAV5-hRKp.RPGR | Subretinal administration of a single low dose of AAV5-hRKp.RPGR in either Phase 1 or Phase 2 of the study (prespecified pooling). AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Retinal Detachment | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctival abrasion | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Program Manager | MeiraGTx | +44 (0)20 3866 4320 | ocularinfo@meiragtx.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 1, 2020 | Oct 30, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 16, 2021 | Oct 30, 2024 | SAP_001.pdf |
Not provided
Not provided
Not provided
Biological
Not provided
Not provided
Not provided
Not provided
| 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. |
| 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. | 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. | 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. | 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. | 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. | Baseline and Month 6 |
| 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 |
| Other: Patient decision |
|
Subretinal administration of a single intermediate dose of AAV5-hRKp.RPGR in either Phase 1 or Phase 2 of the study (prespecified pooling). AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene |
| BG002 | Immediate High Dose AAV5-hRKp.RPGR | Subretinal administration of a single high dose of AAV5-hRKp.RPGR in either Phase 1 or Phase 2 of the study (prespecified pooling). AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene |
| BG003 | Deferred Group | Treatment of participants in this Phase 2 study group was deferred for 6 months |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Subretinal administration of a single low dose of AAV5-hRKp.RPGR AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene |
| OG001 | Immediate Intermediate Dose AAV5-hRKp.RPGR | Subretinal administration of a single intermediate dose of AAV5-hRKp.RPGR AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene |
| OG002 | Immediate High Dose AAV5-hRKp.RPGR | Subretinal administration of a single high dose of AAV5-hRKp.RPGR AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene |
| OG003 | Deferred Group | Treatment of participants in this group was deferred for 6 months |
|
|
| Secondary | 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. | It was prespecified that the results of participants assigned to the low and intermediate dose groups in study Phase 1 and Phase 2 would be pooled and compared to the results of participants in the deferred group before treatment. Data were available for 25 participants in the Immediate Treatment Group and 13 participants in the Deferred Treatment Group | Posted | Mean | Standard Deviation | Number of EDTRS letters | Baseline and Month 6 |
|
|
|
| Secondary | 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. | It was prespecified that the results of participants assigned to the low and intermediate dose groups in study Phase 1 and Phase 2 would be pooled and compared to the results of participants in the deferred group before treatment. Data were available for 23 participants in the Immediate Treatment Group and 10 participants in the Deferred Treatment Group. | Posted | Count of Participants | Participants | Baseline and Month 6 |
|
|
|
| Secondary | 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. | It was prespecified that the results of participants assigned to the low and intermediate dose groups in study Phase 2 would be pooled and compared to the results of participants in the deferred group before treatment. Sixteen participants in the Immediate Treatment Group and all 9 participants in the Deferred Treatment Group completed the LLQ at baseline and Week 26. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Month 6 |
|
|
|
| Secondary | 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. | It was prespecified that the results of participants assigned to the low and intermediate dose groups in study Phase 2 would be pooled and compared to the results of participants in the deferred group before treatment. Sixteen participants in the Immediate Treatment Group and all 9 participants in the Deferred Treatment Group completed the LLQ at baseline and Week 26. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Month 6 |
|
|
|
| Secondary | 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. | It was prespecified that the results of participants assigned to the low and intermediate dose groups in study Phase 2 would be pooled and compared to the results of participants in the deferred group before treatment. Sixteen participants in the Immediate Treatment Group and all 9 participants in the Deferred Treatment Group completed the LLQ at baseline and Week 26. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Month 6 |
|
|
|
| Secondary | 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. | It was prespecified that the results of participants assigned to the low and intermediate dose groups in study Phase 2 would be pooled and compared to the results of participants in the deferred group before treatment. Sixteen participants in the Immediate Treatment Group and all 9 participants in the Deferred Treatment Group completed the LLQ at baseline and Week 26. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Month 6 |
|
|
|
| Secondary | 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. | It was prespecified that the results of participants assigned to the low and intermediate dose groups in study Phase 2 would be pooled and compared to the results of participants in the deferred group before treatment. Sixteen participants in the Immediate Treatment Group and all 9 participants in the Deferred Treatment Group completed the LLQ at baseline and Week 26. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Month 6 |
|
|
|
| 0 |
| 11 |
| 2 |
| 11 |
| 11 |
| 11 |
| EG001 | Immediate Intermediate Dose AAV5-hRKp.RPGR | Subretinal administration of a single intermediate dose of AAV5-hRKp.RPGR in either Phase 1 or Phase 2 of the study (prespecified pooling). AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene | 0 | 17 | 0 | 17 | 17 | 17 |
| EG002 | Immediate High Dose AAV5-hRKp.RPGR | Subretinal administration of a single high dose of AAV5-hRKp.RPGR in either Phase 1 or Phase 2 of the study (prespecified pooling). AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene | 0 | 4 | 0 | 4 | 4 | 4 |
| EG003 | Deferred Group - Before Treatment (Control Group) | Treatment of participants in this Phase 2 group was deferred for 6 months. Data from these deferred-treatment participants (i.e., the Control Group) are included from the signing of the ICF until the time of surgery | 0 | 13 | 0 | 13 | 1 | 13 |
| EG004 | Deferred Group - Low Dose AAV5-hRKp.RPGR - After Treatment | Subretinal administration of a single low dose of AAV5-hRKp.RPGR AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene. Treatment of participants in this Phase 2 group was deferred for 6 months. Data from these deferred treatment participants are included from the time of surgery until the end of the study. | 0 | 7 | 1 | 7 | 7 | 7 |
| EG005 | Deferred Group - Intermediate Dose AAV5-hRKp.RPGR - After Treatment | Subretinal administration of a single intermediate dose of AAV5-hRKp.RPGR AAV5-hRKp.RPGR: AAV gene therapy for defects in the RPGR gene. Treatment of participants in this Phase 2 group was deferred for 6 months. Data from these deferred treatment participants are included from the time of surgery until the end of the study. | 0 | 6 | 0 | 6 | 6 | 6 |
| Uveitis | Eye disorders | MedDRA (Unspecified) | Systematic Assessment | Assessed by the Investigator as ATIMP-related |
|
| Intraocular pressure increased | Investigations | MedDRA (Unspecified) | Systematic Assessment | Assessed by the Investigator as ATIMP-related |
|
| Intraocular pressure increased | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Intraocular pressure decreased | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Anterior chamber cell | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Eye inflammation | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Foreign body sensation in eyes | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Ocular discomfort | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cystoid macular oedema | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Conjunctival hyperaemia | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Posterior capsule opacification | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Retinal haemorrhage | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Uveitis | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Retinal cyst | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Increased appetite | Metabolism and nutrition disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
Not provided
Not provided