X-Linked Retinitis PigmentosaPhase 2NCT06333249

A Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (SKYLINE)

A Phase 2 study testing rAAV2tYF-GRK1-RPGR in people with X-Linked Retinitis Pigmentosa, run by Beacon Therapeutics at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis pigmentosa caused by RPGR mutations. Read more about this study

Who is it for?: Ages 8 to 50 years, men only
Conditions the study is for: X-Linked Retinitis Pigmentosa
What is being tested?: rAAV2tYF-GRK1-RPGR
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 6 sitesUnited States
Study dates: 13 Apr 2021to Feb 2027
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 8 to 50 years
Men only
No healthy volunteers
Child, Adult

Who may be able to join

Provide written informed consent or assent (per local regulation), prior to the conduct of any study-related procedure. Subjects who provide assent must have a parent, guardian, or legal representative provide written informed consent.
Be between 8 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).
Be male and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene
Have a clinical diagnosis of XLRP.
Have a BCVA no better than 75 letters and no worse than 35 letters based on an ETDRS chart at each screening visit.
Be able to perform all tests of visual and retinal function and structure in both eyes based on the subject's reliability, and fixation, per the investigator's discretion.
Have detectable baseline mean macular sensitivity measured by (MAIA) microperimetry, as determined by the investigator and confirmed by the Central Reading Center (CRC).
Have detectable EZ line in both eyes as assessed by SD-OCT and confirmed by the CRC.

Who cannot join

Have other known disease-causing mutations documented in the subject'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.
For subjects with herpes simplex virus (HSV):
Have history of oral or genital herpes and unable and/or unwilling to utilize prophylactic antiviral medication.
Have a history of ocular herpes.
Have active oral or genital herpes or are currently receiving treatment for HSV infection.
Have complicating systemic diseases (e.g., medical conditions causing immunosuppression, active systemic infection) that would preclude the gene transfer or ocular surgery.

Show all 22Show fewer

Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.
Have used anti-coagulant agents that may alter coagulation
Have received any vaccination/immunization within 28 days prior to screening and/or during screening with the exception of the influenza vaccine, which is only exclusionary if they have received the influenza vaccine within 28 days prior to randomization.
Have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening and/or intend to use during screening.
Have previously received any AAV gene therapy product, stem cell therapy, cell-based therapy, or similar biologics.
Ocular Exclusion Criteria (Either Eye):
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
Have significant media opacity impacting evaluation of the retina or vitreous.
Had intraocular surgery within 90 days of study treatment administration.
Have any active ocular/intraocular infection or inflammation
Have a history of steroid-induced raised IOP of >25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.
Have any artificial retinal implant or prosthesis.
Have absence of clear ocular media and/or inadequate pupil dilation to facilitate good quality OCT images.
Have any history of rhegmatogenous retinal detachment.
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.
Have passed the Low Contrast Ora-VNC™ mobility course in either eye or binocularly at any screening visit.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Boston Children's Hosptial
Boston, Massachusetts, 02115
Cincinnati Eye Institute
Cincinnati, Ohio, 45242
Cleveland Clinic
Cleveland, Ohio, 44195
Retina Foundation of the Southwest
Dallas, Texas, 75231
University of Florida
Jacksonville, Florida, 32209
Casey Eye Institute
Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase 1/2 Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) and a Phase 2 Randomized, Controlled, Masked, Multi-center Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Confirmed by a Pathogenic Variant in the RPGR Gene

This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis pigmentosa caused by RPGR mutations.

Read the detailed description

Approximately 12 participants, who were not part of the Phase 1/2 (HORIZON) study, will be enrolled into the dose expansion portion of the study. These participants will be randomized in a 1:1 ratio to 1 of 2 treatment groups (i.e., Group 1 [low dose] and Group 2 [high dose]). Each participant will receive the assigned dose of AGTC-501 in one eye on a single occasion.

Conditions: X-Linked Retinitis Pigmentosa
Being tested: rAAV2tYF-GRK1-RPGR
Keywords: XLRP, retinal degeneration, RPGR, adeno-associated virus, gene therapy, AAV
Medical subject headings: Retinal Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

rAAV2tYF-GRK1-RPGRBiological
Adeno-associated virus vector expressing a human RPGR gene

Study groups in NCT06333249
Study group	Role	What they receive
Low Dose Group	Experimental	Male subjects at least 8 y/o treated with a lower dose (Dose 2 in RPGR-001 Horizon Phase 1/2 study) of rAAV2tYF-GRK1-RPGR study drug. Receives: Biological: rAAV2tYF-GRK1-RPGR
High Dose Group	Experimental	Male subjects at least 8 y/o treated with a higher dose (Dose 5 in RPGR-001 Horizon Phase 1/2 study) of rAAV2tYF-GRK1-RPGR study drug. Receives: Biological: rAAV2tYF-GRK1-RPGR

What is being measured

The primary outcome is the main question the study is designed to answer.

The difference in the proportion of responding eyes between treated and control eyes in the low dose group and high dose group at 12 months, as measured by MAIA microperimetry, where response is defined as a 7dB or more improvement in at least 5 loci.
Measured: Day 0 - Month 12

Secondary outcomes (11)

Proportion of responding eyes in treated eyes versus control eyes in the low dose group and the high dose group at Month 12 where responder is defined as an ORA-VNC mobility test score improvement of 2 or more luminance levels.
Measured: Day 0 - Month 12
Proportion of responding eyes in treated versus control eyes in the low dose group and the high dose group at Month 12, as measured by MAIA microperimetry, where responder is defined as a 7 dB or more improvement in at least 5 loci within bleb.
Measured: Day 0 - Month 12
Proportion of responding eyes in treated vs control eyes in the low dose group and the high dose group at Month 12, measured by MAIA microperimetry where responder is defined as 7 dB or more improvement in at least 5 loci within the central 16 loci
Measured: Day 0 - Month 12
Difference in mean change from baseline in the central 36 loci (C36) mean sensitivity, as measured by MAIA microperimetry, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.
Measured: Day 0 - Month 12
Difference in mean change from baseline in "within bleb" mean sensitivity, as measured by MAIA microperimetry, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.
Measured: Day 0 - Month 12
Difference in mean change from baseline in central 10 degrees of vision on light adapted static perimetry, as measured by Octopus 900, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.
Measured: Day 0 - Month 12
Difference in mean change from baseline in BCVA, as measured by ETDRS or tumbling "E" chart, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.
Measured: Day 0 - Month 12
Proportion of responding eyes in treated versus control eyes in the low dose group and high dose group at Month 12 where responder is defined as a 10-letter vision gain as measured by ETDRS or tumbling "E" chart.
Measured: Day 0 - Month 12
Difference in mean change from baseline in the EZ area, as measured by SD-OCT, in treated eyes versus control eyes in the low dose group and high dose group at Month 12 Visit.
Measured: Day 0 - Month 12
Mean change from baseline in Impact of Vision Impairment (IVI) (Weih et al, 2002; Lamoureaux et al, 2007) or Impact of Vision Impairment for Children (IVI-C) (Cochrane et al, 2008) in the low dose group and high dose group at Month 12 Visit
Measured: Day 0 - Month 12
Mean change from baseline in Patient Global Impressions of Change (PGI-C) and Patient Global Impressions of Severity (PGIS) in the low dose group and high dose group at Month 12 Visit.
Measured: Day 0 - Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Apr 2021Feb 2027

First posted27 Mar 2024
Study start13 Apr 2021
Primary completion11 Apr 2023
Study completionFeb 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for X-Linked Retinitis PigmentosaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: The purpose of the Phase 2 study is to evaluate the efficacy, safety, and tolerability of two doses of AGTC-501 in male subjects between 8 - 50 years of age (inclusive) with XLRP genetically confirmed by at least one pathogenic variant in the RPGR gene. Approximately 12 subjects who meet the inclusion criteria, will be randomized in a 1:1 ratio to 1 of 2 treatment groups. Each subject will receive the assigned dose of AGTC-501 in the study eye; no treatment will be administered in the fellow eye. As treatment outcomes in pediatric vs. adult subjects may differ, randomization to dose groups will be stratified by age. Each subject will receive a central subretinal injection of AGTC-501 at the assigned dose in the central macula of the study eye.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06333249
Sponsor's protocol ID: AGTC-RPGR-001 SKYLINE
Status last verified: Aug 2024
First submitted: 16 Feb 2024
Last updated: 12 Aug 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Wang CY, Chen L, Lin TY, Huang SP. Systematic Identification of Candidate Genes for Inherited Retinal Disease Gene Therapy Integrating Worldwide IRD Cohort and Single-Cell Analysis. J Ophthalmol. 2025 Jun 12;2025:7014745. doi: 10.1155/joph/7014745. eCollection 2025.
PubMed 40547876

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All X-Linked Retinitis Pigmentosa trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1/2 Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) and a Phase 2 Randomized, Controlled, Masked, Multi-center Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Confirmed by a Pathogenic Variant in the RPGR Gene
ClinicalTrials.gov ID: NCT06333249
Acronym / sponsor ID: AGTC-RPGR-001 SKYLINE
Conditions: X-Linked Retinitis Pigmentosa
Keywords: XLRP, retinal degeneration, RPGR, adeno-associated virus, gene therapy, AAV
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 14 participants (actual)
Lead sponsor: Beacon TherapeuticsIndustry (pharma, biotech, devices)
Study start: 13 Apr 2021 (actual)
Primary completion: 11 Apr 2023 (actual)
Study completion: Feb 2027 (estimated)
First posted: 27 Mar 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis pigmentosa caused by RPGR mutations.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: The purpose of the Phase 2 study is to evaluate the efficacy, safety, and tolerability of two doses of AGTC-501 in male subjects between 8 - 50 years of age (inclusive) with XLRP genetically confirmed by at least one pathogenic variant in the RPGR gene. Approximately 12 subjects who meet the inclusion criteria, will be randomized in a 1:1 ratio to 1 of 2 treatment groups. Each subject will receive the assigned dose of AGTC-501 in the study eye; no treatment will be administered in the fellow eye. As treatment outcomes in pediatric vs. adult subjects may differ, randomization to dose groups will be stratified by age. Each subject will receive a central subretinal injection of AGTC-501 at the assigned dose in the central macula of the study eye.

Arm	Type	Receives
Low Dose Group	Experimental	Biological: rAAV2tYF-GRK1-RPGRMale subjects at least 8 y/o treated with a lower dose (Dose 2 in RPGR-001 Horizon Phase 1/2 study) of rAAV2tYF-GRK1-RPGR study drug.
High Dose Group	Experimental	Biological: rAAV2tYF-GRK1-RPGRMale subjects at least 8 y/o treated with a higher dose (Dose 5 in RPGR-001 Horizon Phase 1/2 study) of rAAV2tYF-GRK1-RPGR study drug.

Who may qualify

Ages: 8 to 50 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (8 listed)

Provide written informed consent or assent (per local regulation), prior to the conduct of any study-related procedure. Subjects who provide assent must have a parent, guardian, or legal representative provide written informed consent.
Be between 8 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).
Be male and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene
Have a clinical diagnosis of XLRP.
Have a BCVA no better than 75 letters and no worse than 35 letters based on an ETDRS chart at each screening visit.

Key exclusion criteria (22 listed)

Have other known disease-causing mutations documented in the subject'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.
For subjects with herpes simplex virus (HSV):
Have complicating systemic diseases (e.g., medical conditions causing immunosuppression, active systemic infection) that would preclude the gene transfer or ocular surgery.
Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.
Have used anti-coagulant agents that may alter coagulation

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
rAAV2tYF-GRK1-RPGRAdeno-associated virus vector expressing a human RPGR gene	Biological	High Dose Group, Low Dose Group

Primary outcome

The difference in the proportion of responding eyes between treated and control eyes in the low dose group and high dose group at 12 months, as measured by MAIA microperimetry, where response is defined as a 7dB or more improvement in at least 5 loci.
Time frame: Day 0 - Month 12

11 secondary outcomes

Proportion of responding eyes in treated eyes versus control eyes in the low dose group and the high dose group at Month 12 where responder is defined as an ORA-VNC mobility test score improvement of 2 or more luminance levels.
Time frame: Day 0 - Month 12
Proportion of responding eyes in treated versus control eyes in the low dose group and the high dose group at Month 12, as measured by MAIA microperimetry, where responder is defined as a 7 dB or more improvement in at least 5 loci within bleb.
Time frame: Day 0 - Month 12
Proportion of responding eyes in treated vs control eyes in the low dose group and the high dose group at Month 12, measured by MAIA microperimetry where responder is defined as 7 dB or more improvement in at least 5 loci within the central 16 loci
Time frame: Day 0 - Month 12
Difference in mean change from baseline in the central 36 loci (C36) mean sensitivity, as measured by MAIA microperimetry, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.
Time frame: Day 0 - Month 12
Difference in mean change from baseline in "within bleb" mean sensitivity, as measured by MAIA microperimetry, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.
Time frame: Day 0 - Month 12
Difference in mean change from baseline in central 10 degrees of vision on light adapted static perimetry, as measured by Octopus 900, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.
Time frame: Day 0 - Month 12
Difference in mean change from baseline in BCVA, as measured by ETDRS or tumbling "E" chart, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.
Time frame: Day 0 - Month 12
Proportion of responding eyes in treated versus control eyes in the low dose group and high dose group at Month 12 where responder is defined as a 10-letter vision gain as measured by ETDRS or tumbling "E" chart.
Time frame: Day 0 - Month 12
Difference in mean change from baseline in the EZ area, as measured by SD-OCT, in treated eyes versus control eyes in the low dose group and high dose group at Month 12 Visit.
Time frame: Day 0 - Month 12
Mean change from baseline in Impact of Vision Impairment (IVI) (Weih et al, 2002; Lamoureaux et al, 2007) or Impact of Vision Impairment for Children (IVI-C) (Cochrane et al, 2008) in the low dose group and high dose group at Month 12 Visit
Time frame: Day 0 - Month 12
Mean change from baseline in Patient Global Impressions of Change (PGI-C) and Patient Global Impressions of Severity (PGIS) in the low dose group and high dose group at Month 12 Visit.
Time frame: Day 0 - Month 12

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2024.
Derived from this study: PubMed 40547876Wang CY, Chen L, Lin TY, Huang SP. Systematic Identification of Candidate Genes for Inherited Retinal Disease Gene Therapy Integrating Worldwide IRD Cohort and Single-Cell Analysis. J Ophthalmol. 2025 Jun 12;2025:7014745. doi: 10.1155/joph/7014745. eCollection 2025.

Related trials for X-Linked Retinitis Pigmentosa

RecruitingObservational study
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Active, not recruitingPhase 2
A Follow-on Study for Second-Eye Treatment for Participants Previously Treated With Gene Therapy for X-Linked Retinitis Pigmentosa (XLRP)
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A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing rAAV2tYF-GRK1-RPGR in people with X-Linked Retinitis Pigmentosa, run by Beacon Therapeutics at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 12 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The difference in the proportion of responding eyes between treated and control eyes in the low dose group and high dose group at 12 months, as measured by MAIA microperimetry, where response is defined as a 7dB or more improvement in at least 5 loci. (time frame: Day 0 - Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06333249, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2024.