Adeno-associated virus vector containing the human RPGR gene for X-linked retinitis pigmentosa (XLRP)|Retinitis pigmentosa

Inclusion criteria

• {"criterion_text":"- Provide written informed consent or assent (per local regulation), prior to the conduct of any study-related procedure. Participants who provide assent must have a parent, guardian, or legal representative provide written informed consent.\n- Be between 12 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).\n- Be male (XY chromosome) and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene within exons 1-14 and/or ORF15 from a Clinical Laboratory Improvement Amendments of 1988 (CLIA)-certified laboratory.\n- Have a clinical diagnosis of XLRP.\n- Be in good general health to withstand subretinal surgery and perioperative medications based on a complete physical examination and hematology and clinical chemistry evaluations performed at screening.\n- Be able and willing, as assessed by the Investigator, to follow study instructions, complete study assessments, comply with the protocol, and attend study visits for the duration of the study.\n- If the participant has a parent or caregiver, the parent or caregiver must be able to follow study instructions, comply with the protocol, and attend study visits with the participant, as required.\n- Have a BCVA ≤ 78 letters (approximately Snellen, 20/32) and ≥ 34 letters (approximately Snellen, 20/200) based on an ETDRS chart at each screening visit. ETDRS letter score is the main VA inclusion criterion for participants. Participants unable to read the ETDRS letters may utilize a tumbling “E” chart for BCVA assessments.\n- Have a LLVA ≤64 letters (approximately Snellen 20/50) in the study eye based on an ETDRS chart at each screening visit. Participants unable to read the ETDRS letters may utilize a tumbling “E” chart for LLVA assessments.\n- Be able to perform all tests of visual and retinal function and structure in both eyes based on the participant’s reliability, and fixation, in the study eye per the Investigator’s discretion.\n- Have detectable baseline mean macular sensitivity measured by MAIA microperimetry, between 1-12 dB in the study eye, as determined by the Investigator and confirmed by the Central Reading Center (CRC), with fixation loss ≤20% at each screening visit.\n- Have a detectable sub-foveal ellipsoid zone (EZ) line as assessed by SD-OCT in the study eye and confirmed by the CRC.\n- If both eyes meet all entry criteria, the study eye is the worse-seeing eye as measured by ETDRS BCVA. If both eyes are eligible and have the same BCVA, the choice of study eye will be at the discretion of the Investigator and/or Surgeon."}

Exclusion criteria

• {"criterion_text":"- Have other known disease-causing mutations documented in the participant’s medical history or identified through a retinal dystrophy gene panel that, in the opinion of the Investigator, would interfere with the potential therapeutic effect of the study agent or the quality of the assessments\n- For participants with herpes simplex virus (HSV): a. Have history of oral or genital herpes and are unable and/or unwilling to utilize prophylactic antiviral medication. b. Have a history of ocular herpes. c. Have active oral or genital herpes or are currently receiving treatment for HSV infection.\n- Are currently participating or recently participated in any other research protocol involving investigational agents or therapies that would make the participant unsuitable for the study. Recent participation is defined as participation within 90 days of initial screening for this study OR within 10 half-lives of the investigational drug, whichever is longer.\n- Have previously received any AAV gene therapy product, stem cell therapy, cell-based therapy, or similar biologics.\n- Have pre-existing eye conditions that would preclude the planned surgery, interfere with the interpretation of study endpoints, or increase the risk of surgical complications (e.g., corneal opacities, diabetic retinopathy, retinal vasculitis, glaucoma, active cystoid macular edema [CME]).\n- Have significant media opacity impacting evaluation of the retina or vitreous. This includes cataracts considered to be a major contributor to reducing visual acuity and/or if the participant is likely to require cataract extraction within 3 months of study treatment administration.\n- Had intraocular surgery within 90 days of study treatment administration (Day 1).\n- Have any active ocular/intraocular infection or inflammation (e.g., severe blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis, idiopathic or autoimmune-associated uveitis, or herpetic lesions).\n- Have a history of corticosteroid-induced raised intraocular pressure (IOP) of >25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.\n- Have any artificial retinal implant or prosthesis.\n- Have absence of clear ocular media and/or inadequate pupil dilation to facilitate good quality SD-OCT images.\n- Have any history of rhegmatogenous retinal detachment.\n- Have myopia (spherical equivalent) exceeding −10 diopters (or axial length of >30 mm if PI deems it appropriate to measure) or presence of pathologic myopia in the study eye.\n- Have passed the Low Contrast Ora-VNC mobility course ≤0.35 lux light level in either eye or binocularly at any screening visit.\n- Have complicating systemic diseases (e.g., medical conditions causing immunosuppression, autoimmunity, active systemic infection) that would preclude the gene transfer or ocular surgery if not adequately managed or treated.\n- Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.\n- Have used anti-coagulant agents that may alter coagulation (e.g., warfarin, heparin, apixaban, or high dose docosahexaenoic acid [DHA; fish oil]) within 7 days prior to study treatment administration (ibuprofen, aspirin, or similar are acceptable).\n- Have received any vaccination/immunization within 28 days prior to screening and/or during screening, except for the influenza vaccine, which is only exclusionary if they have received the influenza vaccine within 28 days prior to randomization.\n- Have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening and/or intend to use during screening. Corticosteroids used on an as-needed basis administered by insufflation, inhalation, or local administration to the skin and mucosa, such as Symbicort (budesonide/formoterol), Flonase (fluticasone propionate), and skin creams and ointments containing corticosteroids shall not be exclusionary.\n- If sexually active or planning to become sexually active, are unwilling to use barrier contraception for 3 months following treatment administration.\n- Have any other condition or reason that, in the opinion of the Investigator, would prevent a participant from completing study assessments during the study."}

Primary endpoints

• {"endpoint_text":"- The primary efficacy endpoint in Europe is the change from baseline in mean sensitivity across the whole grid, as measured by MAIA microperimetry, at Month 12","definition_or_measurement_approach":"Change from baseline in mean sensitivity across the whole MAIA microperimetry grid at Month 12, measured by MAIA microperimetry and assessed versus baseline (Central Reading Center confirmation)."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in mobility test score at Month 12 as measured by the Ora-VNC mobility course\n- Change from baseline in mean sensitivity across the whole grid, as measured by MAIA microperimetry at Month 18\n- Response at Month 12, as measured by MAIA microperimetry, where response is defined as a ≥7 decibel (dB) visual sensitivity improvement from baseline in at least 5 loci\n- Change from baseline in mobility test score at Month 12 as measured by the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course\n- Change from baseline in full-field stimulus threshold (FST) at Month 12\n- Change from baseline in mean sensitivity across the central 4 loci, as measured by MAIA microperimetry, at Month 12\n- Proportion of participants with a ≥15 letter increase from baseline in LLVA at Month 18 and 24\n- Change in low-luminance deficit (LLD), defined as the difference between BCVA and LLVA Month 12\n- Change from baseline in BCVA over time as assessed by an Early Treatment of Diabetic Retinopathy (ETDRS) or Tumbling E chart at Month 12\n- Response by Ora-VNC where response is defined as a mobility test score increase of 2 or more luminance levels at Month 12\n- Change from baseline in mean sensitivity across the whole grid, as measured by MAIA microperimetry at Month 24\n- Response at Month 18 and 24, as measured by MAIA microperimetry, where response is defined as a ≥7 decibel (dB) visual sensitivity improvement from baseline in at least 5 loci\n- Change from baseline in full-field stimulus threshold (FST) at Month 24\n- Change from baseline in mean sensitivity across the central 4 loci, as measured by MAIA microperimetry, at Month 18 and Month 24\n- Proportion of participants with a ≥10 letter increase from baseline in LLVA at Month 12, 18 and 24\n- Change in low-luminance deficit (LLD), defined as the difference between BCVA and LLVA Month 18 and 24\n- Change from baseline in BCVA over time as assessed by an Early Treatment of Diabetic Retinopathy (ETDRS) or Tumbling E chart at Month 18 and 24\n- Change from baseline in mobility test score at Month 18 and 24 as measured by the Ora-VNC mobility course\n- Response by Ora-VNC where response is defined as a mobility test score increase of 2 or more luminance levels at Month 18 and 24\n- Efficacy: Change from baseline in spectral-domain optical coherence tomography (SD-OCT) EZ line over time\n- Efficacy: Response over time, as measured by MAIA microperimetry, defined as ≥7 dB visual sensitivity improvement from baseline in 5 prespecified loci\n- Efficacy: Change from baseline in domain scores from the Michigan Retinal Degeneration Questionnaire (MRDQ), over time\n- Safety: The primary safety endpoint is the number and proportion of participants with ocular/non-ocular AEs","definition_or_measurement_approach":"Each endpoint is defined in the protocol and measured using specified instruments: MAIA microperimetry for mean sensitivity and response definitions (≥7 dB improvement in prespecified loci), Ora-VNC and MOST-VR mobility courses for mobility scores and response definitions (2 luminance levels), FST for full-field stimulus threshold, ETDRS or Tumbling E charts for BCVA/LLVA and letter-change outcomes, SD-OCT EZ line measurements for anatomical change, MRDQ domain scores for patient-reported outcomes, and adverse events counted and categorized for safety."}

Methods

• Patient Recruitment & Surgical Scheduling provided by Serva Health LLC (listed sponsor duty: "Patient Recruitment & Surgical Scheduling").
• Patient Travel & Reimbursement and Site Payments managed by Block Clinical Inc. (listed sponsor duty: "Patient Travel & Reimbursement Site Payments").
• Patient recruitment support and surgical scheduling support duties identified among sponsor third parties (roles listed for Serva Health LLC and others).

Spain

Earliest CTIS Part Ii Submission Date

22-07-2024

Latest Decision Or Authorization Date

17-09-2024

Processing Time Days

57

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Beacon Therapeutics (USA) Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

TFS Trial Form Support International AB

Responsibilities

Multiple operational trial support functions (numerous sponsor duty codes listed)

Name

Syneos Health Inc.

Responsibilities

Pharmacovigilance & safety database

Name

Almac Clinical Services Limited

Responsibilities

Storage and Shipment of AGTC-501 drug product and diluent & Temperature excursion reporting

Name

Everest Clinical Research Corporation

Responsibilities

Data management, biostatistics, statistical programming, and DSMC services & IRT system

Name

Block Clinical Inc.

Responsibilities

Patient Travel & Reimbursement Site Payments

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Lab sample processing and analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Block Clinical Inc.","duties_or_roles":"Patient Travel & Reimbursement Site Payments","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Boston Image Reading Center LLC","duties_or_roles":"Certification of imaging equipment and technicians/ photographers & Central Image Reading Center","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Digital/IT systems (sponsor duty code provided)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Optymedge LLC","duties_or_roles":"BCVA and LLVA lane and examiner certifications","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Sweden","full_name":"TFS Trial Form Support International AB","duties_or_roles":"Multiple sponsor duties (codes listed) including trial form support and various operational roles","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Storage and Shipment of AGTC-501 drug product and diluent & Temperature excursion reporting","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Pharmacovigilance & safety database","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Serva Health LLC","duties_or_roles":"Patient Recruitment & Surgical Scheduling","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Streetlab","duties_or_roles":"Virtual Reality Mobility Course & Central Reading Center","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"Data management, biostatistics, statistical programming, and DSMC services & IRT system","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Preventiongenetics LLC","duties_or_roles":"Genetic testing services (sponsor duty code for testing)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Ora Europe Limited","duties_or_roles":"Mobility Course installation & Central Reading Center","organisation_type":"Pharmaceutical company"}