A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With XLRP

X-Linked Retinitis Pigmentosa Clinical Trial

Official title:

A Randomized, Controlled, Masked, Multi-center Study Evaluating the Efficacy, Safety, and Tolerability of Two Doses of AGTC-501 Compared to an Untreated Control Group in Male Participants With X-linked Retinitis Pigmentosa

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04850118
• Other study ID #: AGTC-RPGR-002
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 14, 2024
• Est. completion date: October 2029

Study information

• Verified date: April 2024
• Source: Beacon Therapeutics
• Contact: Serva Health
• Phone: 855-467-2364
• Email: ProviderSupport[@]scenictrials.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate and compare the safety, efficacy, and tolerability of 2 doses of a recombinant adeno-associated virus vector (AGTC-501) to an untreated control group in male participants with X-linked retinitis pigmentosa caused by RPGR mutations.

Description:

This study is a randomized, controlled, masked, multi-center study evaluating and comparing 2 doses of AGTC-501 to an untreated control group. A single subretinal injection of AGTC-501 Dose 1 or Dose 2 will be administered in participants in 2 treatment groups while participants in the untreated control group will be followed and evaluated, after which they will be evaluated to determine eligibility to receive treatment with AGTC-501 Dose 2. Approximately 75 eligible male participants between 12 and 50 years of age (inclusive) will be randomized in a 1:1:1 ratio to 1 of 3 groups.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: October 2029
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 50 Years

Eligibility

General Inclusion Criteria:

1. 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.

2. Be between 12 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).

3. Be male (XY chromosome) and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene.

4. Have a clinical diagnosis of XLRP.

5. 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.

Ocular Inclusion Criteria (Study Eye):

6. Have a BCVA = 78 letters (approximately Snellen, 20/32) and = 34 letters (approximately Snellen, 20/200)

7. Have a LLVA =64 letters (approximately Snellen 20/50) in the study eye

8. 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.

9. Have detectable baseline mean macular sensitivity .

10. Have a detectable sub-foveal ellipsoid zone (EZ) line as assessed by SD-OCT in the study eye and confirmed by the CRC.

11. If study eye will be at the discretion of the Investigator and/or Surgeon.

General Exclusion Criteria:

1. 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.

2. For participants with herpes simplex virus (HSV):

1. Have history of oral or genital herpes and unable and/or unwilling to utilize prophylactic antiviral medication.

2. Have a history of ocular herpes.

3. Have active oral or genital herpes or are currently receiving treatment for HSV infection.

3. Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.

4. 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).

5. 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.

6. If sexually active or planning to become sexually active, are unwilling to use barrier contraception for 3 months following treatment administration.

7. Are currently participating or recently participated in any other research

8. Have previously received any AAV gene therapy product, stem cell therapy, cell-based therapy, or similar biologics.

9. Have significant media opacity impacting evaluation of the retina or vitreous. administration.

10. Had intraocular surgery within 90 days of study treatment administration.

11. 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).

12. Have a history of corticosteroid-induced raised IOP of >25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.

13. Have any artificial retinal implant or prosthesis.

14. Have absence of clear ocular media and/or inadequate pupil dilation to facilitate good quality SD-OCT images.

15. Have any history of rhegmatogenous retinal detachment.

16. Have myopia (spherical equivalent) exceeding -10 diopters (or axial length of >30 mm if the Principal Investigator [PI] deems it appropriate to measure) or presence of pathologic myopia in the study eye.

17. Have passed the Low Contrast Ora-VNC mobility course at =0.35 lux light level in either eye or binocularly at any screening visit.

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa
• X-Linked Retinitis Pigmentosa

Intervention

Biological:
• rAAV2tYF-GRK1-hRPGRco
Adeno-associated virus vector expressing a human RPGR gene

Drug:
• Control
Untreated Control Group 3

Locations

Country	Name	City	State
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	University of Florida Health Jacksonville, Department of Ophthalmology	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Beacon Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number and proportion of treatment-emergent ocular/non-ocular adverse events	Ocular/non-ocular adverse events are collected the duration of the trial	Day 0 - Year 5
Primary	The proportion of participants with a =15 letter increase from baseline in LLVA	LLVA(Low Luminance Visual Acuity) will be determined using standard ETDRS (Early Treatment of Diabetic Retinopathy) visual acuity or tumbling "E" chart	Day 0 - Month 12
Secondary	Change from baseline in mobility test score at Month 12	Functional vision will be assessed using an Ora-VNC mobility course	Day 0 - Month 12
Secondary	Change from baseline in mean sensitivity across the whole grid, as measured by MAIA microperimetry	As assessed by MAIA (Macular Integrity Assessment) microperimetry - assess photoreceptor function under low-light	Day 0 - Month 18
Secondary	Visual sensitivity improvement from baseline in at least 5 loci	As measured by MAIA (Macular Integrity Assessment - assess photoreceptor function under low-light) microperimetry, where response is defined as a =7 decibel (dB)	Month 12
Secondary	Change from baseline in mobility test score	As measured by the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course	Month 12
Secondary	Change from baseline in full-field stimulus threshold (FST)	Full-field stimulus threshold (FST) measures the sensitivity of the visual field by testing for the lowest luminance flash which elicits a visual sensation perceived	Month 12
Secondary	Change from baseline in mean sensitivity across the central 4 loci	As measured by MAIA (Macular Integrity Assessment) microperimetry; assess photoreceptor function under low-light	Month 12
Secondary	Proportion of participants with a =15 letter increase from baseline	LLVA - (Low Luminance Visual Acuity) will be determined using standard ETDRS (Early Treatment of Diabetic Retinopathy) visual acuity testing or tumbling "E" chart	Month 18 and Month 24
Secondary	Change in low-luminance deficit (LLD), defined as the difference between BCVA and LLVA	BCVA (Best Corrected Visual Acuity) / LLVA (Low Luminance Visual Acuity) will be determined using standard ETDRS (Early Treatment of Diabetic Retinopathy) visual acuity or tumbling "E" chart	Month 12
Secondary	Change from baseline in BCVA over time as assessed by an Early Treatment of Diabetic Retinopathy (ETDRS) or Tumbling E chart at Month 12	BCVA (Best Corrected Visual Acuity) as assessed by an Early Treatment of Diabetic Retinopathy (ETDRS) or Tumbling E chart	Month 12
Secondary	Response by Ora-VNC where response is defined as a mobility test score increase of 2 or more luminance levels at Month 12	As assessed by functional testing, Ora-VNC mobility course	Month 12
Secondary	Change from baseline in mean sensitivity across the whole grid, as measured by MAIA microperimetry at Month 24	As assessed by MAIA (Macular Integrity Assessment) microperimetry	Month 24
Secondary	Visual sensitivity improvement from baseline in at least 5 loci	As measured by MAIA (Macular Integrity Assessment) microperimetry, where response is defined as a =7 decibel (dB)	Month 18 and 24
Secondary	Change from baseline in full-field stimulus threshold (FST) at Month 24	As assessed by full-field threshold (FST) ; (FST)measures the sensitivity of the visual field by testing for the lowest luminance flash which elicits a visual sensation perceived	Month 24
Secondary	Change from baseline in mean sensitivity across the central 4 loci, as measured by MAIA microperimetry, at Month 18 and Month 24	As measured by MAIA ((Macular Integrity Assessment) microperimetry	Month 18 and 24
Secondary	Proportion of participants with a =10 letter increase from baseline in LLVA at Month 12, 18 and 24	LLVA (Low Luminance Visual Acuity) twill be determined using standard ETDRS visual acuity or tumbling "E" chart	Month 12, 18 and 24
Secondary	Change in low-luminance deficit (LLD), defined as the difference between BCVA and LLVA Month 18 and 24	Defined as the difference between BCVA/LLVA /LLVA ) Low Luminance Visual Acuity) will be determined using standard ETDRS visual acuity or tumbling "E" chart	Month 18 and 24
Secondary	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	As assessed by ETDRS or Tumbling E chart.	Month 18 and 24
Secondary	Change from baseline in mobility test score at Month 18 and 24 as measured by the Ora- VNC mobility course	as assessed by functional assessment Ora-VNC mobility course	Month 18 and 24
Secondary	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	As assessed by functional assessment Ora-VNC mobility course	Month 18 and 24