X-Linked Retinitis PigmentosaPhase 2NCT06275620

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

A Phase 2 study testing AGTC-501 (high dose and standard corticosteroid regimen), AGTC-501 (low dose and standard corticosteroid regimen) and AGTC-501 (high dose and modified corticosteroid regimen) in people with X-Linked Retinitis Pigmentosa, run by Beacon Therapeutics at 7 sites in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts

Official record

Search all trials

Trial summary

This Phase 2 study is a non-randomized, open-label, study of the safety of AGTC-501 in participants with XLRP who have previously been treated with a full-length AAV vector-based gene therapy targeting RPGR protein. Read more about this study

Who is it for?: Ages 12 years and older, men only
Conditions the study is for: X-Linked Retinitis Pigmentosa
What is being tested?: AGTC-501 (high dose and standard corticosteroid regimen), AGTC-501 (low dose and standard corticosteroid regimen) and AGTC-501 (high dose and modified corticosteroid regimen)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 7 sitesUnited States
Study dates: 14 Nov 2023to Dec 2029
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 12 years and older
Men only
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Be ≥12 years of age
Have one eye previously treated with an AAV vector-based gene therapy designed to provide full-length functioning RPGR protein.
Have a BCVA no better than 78 letters and no worse than 34 letters
Be able to perform all tests of visual and retinal function and structure in both eyes based on the participant'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 the study eye as assessed by SD-OCT and confirmed by the CRC.

Who cannot join

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.
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
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.

Trial locations and contacts

7 sites in 1 country. Contact the study team or a site near you to ask about taking part.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Boston Children's Hospital
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
Bascom Palmer Eye Institute
Miami, Florida, 33136
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 Participants With X-linked Retinitis Pigmentosa

Read the detailed description

This is a Phase 2, open-label, multicenter study to evaluate the safety of 2 doses of AGTC-501 administered as a single subretinal injection in participants with XLRP who have previously been treated with a full-length AAV vector-based gene therapy targeting RPGR protein.

The trial includes a screening period of up to 60 days and a 5 year study period.

Each participant will receive a single subretinal injection of one of two dose levels of AGTC-501 in their previously untreated eye. There will be 3 groups. Group 1 will receive the high dose and include up to 12 participants, Group 2 will receive the low dose and will include 6 participants, and Group 3 will include ~3-6 participants. Participants in Groups 1 and 2 will receive the standard corticosteroid regimen. A single subretinal injection of the high dose AGTC-501 will be administered to participants in Group 1 (n = 12), while participants in Group 2 (n = 6) will receive a single subretinal injection of low dose AGTC-501. Group 2 (low dose AGTC-501, Standard Steroid) will be dosed before moving to Group 3. After 6 Group 1 (high dose) study participants reach post-operative Month 1, all data will be reviewed by the DSMC. If no safety signals arise, additional participants, Group 3 (n ~ 3-6), will receive a single subretinal injection of the high dose with a modified course of corticosteroids.

Conditions: X-Linked Retinitis Pigmentosa
Being tested: AGTC-501 (high dose and standard corticosteroid regimen), AGTC-501 (low dose and standard corticosteroid regimen), AGTC-501 (high dose and modified corticosteroid regimen)
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.

AGTC-501 (high dose and standard corticosteroid regimen)Biological
Adeno-associated virus vector expressing a human RPGR gene
AGTC-501 (low dose and standard corticosteroid regimen)Biological
Adeno-associated virus vector expressing a human RPGR gene
AGTC-501 (high dose and modified corticosteroid regimen)Biological
Adeno-associated virus vector expressing a human RPGR gene

Study groups in NCT06275620
Study group	Role	What they receive
Group 1 (High Dose, Standard Corticosteroid)	Experimental	Following a pars plana vitrectomy, the previously untreated eye of participants (n=up to 12) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks. Receives: Biological: AGTC-501 (high dose and standard corticosteroid regimen)
Group 2 (Low Dose, Standard Corticosteroid)	Experimental	Following a pars plana vitrectomy, the previously untreated eye of participants (n=6) will receive a central subretinal injection at the low dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks. Receives: Biological: AGTC-501 (low dose and standard corticosteroid regimen)
Group 3 (High Dose, Modified Corticosteroid)	Experimental	Following a pars plana vitrectomy, the previously untreated eye of participants (n=approximately 3-6) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. Participants in Group 3 (high dose, modified corticosteroid) will have a more rapid corticosteroid taper. Receives: Biological: AGTC-501 (high dose and modified corticosteroid regimen)

What is being measured

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

The primary safety outcome is the number of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs).
Measured: Day 0 - Month 12
The primary safety outcome is the proportion of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs).
Measured: Day 0 - Month 12

Secondary outcomes (12)

The number of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs.
Measured: Day 0 - Month 12
The proportion of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs.
Measured: Day 0 - Month 12
Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Macular Integrity Assessment) microperimetry, assess photoreceptor function under low light
Measured: Day 0 - Month 12
Response, as measured by MAIA (Macular Integrity Assessment) microperimetry, where response is defined as a greater than or equal to 7 decibel (dB) visual sensitivity improvement from baseline in at least 5 loci.
Measured: Day 0 - Month 12
Change from baseline in full-field stimulus threshold (FST)
As assessed by full-field stimulus threshold (FST); FST measures the sensitivity of the visual field by testing for the lowest luminance flash which elicits a visual sensation perceived
Measured: Day 0 - Month 12
Change from baseline in Best Corrected Visual Acuity (BCVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
Measured: Day 0 - Month 12
Change from baseline in Low Luminance Visual Acuity (LLVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
Measured: Day 0 - Month 12
Proportion of responding eyes in treated versus control eyes at Month 12 where responder is defined as an improvement of at least 15-letters on low-luminance visual acuity (LLVA)
Measured: Day 0 - Month 12
Change from baseline in ellipsoid zone (EZ) area measured by spectral domain optical coherence tomography (SD OCT)
Measured: Day 0 - Month 12
Change from baseline in seven domain scores from a Michigan Retinal Degeneration Questionnaire (MRDQ)
Measured: Day 0 - Month 12
Change from baseline in Ora-VNC (visual navigation course) mobility test score
As assessed by functional assessment Ora-VNC (visual navigation course) mobility course
Measured: Day 0 - Month 12
Change from baseline in the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course test score
As measured by the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course
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.

14 Nov 2023Dec 2029

First posted23 Feb 2024
Study start14 Nov 2023
Primary completionNov 2025 (estimated)
Study completionDec 2029 (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: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 24 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06275620
Sponsor's protocol ID: AGTC-RPGR-001 DAWN
Status last verified: Oct 2024
First submitted: 16 Feb 2024
Last updated: 30 Oct 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

Interested in taking part?

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 sites and contacts

RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
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)
X-Linked Retinitis Pigmentosa
Active, not recruitingPhase 3
A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
Retinitis Pigmentosa
Active, not recruitingPhase 3
Follow-up Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene
X-Linked Retinitis Pigmentosa
RecruitingObservational study
A Natural History Study Seeks to Understand the Clinical, Genomic, Pharmacological, Laboratory, and Dietary Determinates of Pyrimidine and Purine Metabolism Disorders
AMPD3, OMIM*102772, AMP Deaminase Deficiency, AK1, OMIM *103000, Adenylate Kinase Deficiency

All X-Linked Retinitis Pigmentosa trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Oct 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 Participants With X-linked Retinitis Pigmentosa
ClinicalTrials.gov ID: NCT06275620
Acronym / sponsor ID: AGTC-RPGR-001 DAWN
Conditions: X-Linked Retinitis Pigmentosa
Keywords: XLRP, retinal degeneration, RPGR, adeno-associated virus, gene therapy, AAV
Phase: Phase 2
Study type: Interventional
Recruitment status: Enrolling by invitation
Enrolment: 24 participants (estimated)
Lead sponsor: Beacon TherapeuticsIndustry (pharma, biotech, devices)
Study start: 14 Nov 2023 (actual)
Primary completion: Nov 2025 (estimated)
Study completion: Dec 2029 (estimated)
First posted: 23 Feb 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.

Detailed description

The trial includes a screening period of up to 60 days and a 5 year study period.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Group 1 (High Dose, Standard Corticosteroid)	Experimental	Biological: AGTC-501 (high dose and standard corticosteroid regimen)Following a pars plana vitrectomy, the previously untreated eye of participants (n=up to 12) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks.
Group 2 (Low Dose, Standard Corticosteroid)	Experimental	Biological: AGTC-501 (low dose and standard corticosteroid regimen)Following a pars plana vitrectomy, the previously untreated eye of participants (n=6) will receive a central subretinal injection at the low dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks.
Group 3 (High Dose, Modified Corticosteroid)	Experimental	Biological: AGTC-501 (high dose and modified corticosteroid regimen)Following a pars plana vitrectomy, the previously untreated eye of participants (n=approximately 3-6) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. Participants in Group 3 (high dose, modified corticosteroid) will have a more rapid corticosteroid taper.

Who may qualify

Ages: 12 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (6 listed)

Be ≥12 years of age
Have one eye previously treated with an AAV vector-based gene therapy designed to provide full-length functioning RPGR protein.
Have a BCVA no better than 78 letters and no worse than 34 letters
Be able to perform all tests of visual and retinal function and structure in both eyes based on the participant'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).

Key exclusion criteria (5 listed)

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.
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
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.

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
AGTC-501 (high dose and standard corticosteroid regimen)Adeno-associated virus vector expressing a human RPGR gene	Biological	Group 1 (High Dose, Standard Corticosteroid)
AGTC-501 (low dose and standard corticosteroid regimen)Adeno-associated virus vector expressing a human RPGR gene	Biological	Group 2 (Low Dose, Standard Corticosteroid)
AGTC-501 (high dose and modified corticosteroid regimen)Adeno-associated virus vector expressing a human RPGR gene	Biological	Group 3 (High Dose, Modified Corticosteroid)

Primary outcome

The primary safety outcome is the number of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs).
Time frame: Day 0 - Month 12
The primary safety outcome is the proportion of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs).
Time frame: Day 0 - Month 12

12 secondary outcomes

The number of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs.
Time frame: Day 0 - Month 12
The proportion of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs.
Time frame: Day 0 - Month 12
Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Macular Integrity Assessment) microperimetry, assess photoreceptor function under low light
Time frame: Day 0 - Month 12
Response, as measured by MAIA (Macular Integrity Assessment) microperimetry, where response is defined as a greater than or equal to 7 decibel (dB) visual sensitivity improvement from baseline in at least 5 loci.
Time frame: Day 0 - Month 12
Change from baseline in full-field stimulus threshold (FST)
Time frame: Day 0 - Month 12
Change from baseline in Best Corrected Visual Acuity (BCVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
Time frame: Day 0 - Month 12
Change from baseline in Low Luminance Visual Acuity (LLVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
Time frame: Day 0 - Month 12
Proportion of responding eyes in treated versus control eyes at Month 12 where responder is defined as an improvement of at least 15-letters on low-luminance visual acuity (LLVA)
Time frame: Day 0 - Month 12
Change from baseline in ellipsoid zone (EZ) area measured by spectral domain optical coherence tomography (SD OCT)
Time frame: Day 0 - Month 12
Change from baseline in seven domain scores from a Michigan Retinal Degeneration Questionnaire (MRDQ)
Time frame: Day 0 - Month 12
Change from baseline in Ora-VNC (visual navigation course) mobility test score
Time frame: Day 0 - Month 12
Change from baseline in the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course test score
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 30 Oct 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
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
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)
X-Linked Retinitis Pigmentosa
Active, not recruitingPhase 3
A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
Retinitis Pigmentosa
Active, not recruitingPhase 3
Follow-up Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene
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RecruitingObservational study
A Natural History Study Seeks to Understand the Clinical, Genomic, Pharmacological, Laboratory, and Dietary Determinates of Pyrimidine and Purine Metabolism Disorders
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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.

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

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

Questions about this trial

What is this clinical trial studying?

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 6 inclusion and 5 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: enrolling by invitation, as of the sponsor's last update on 30 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 primary safety outcome is the number of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs). (time frame: Day 0 - Month 12). The study lists 2 primary outcomes in all. 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 NCT06275620, 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 30 Oct 2024.