X-linked RetinoschisisPhase 1/2NCT02416622
Safety and Efficacy of rAAV-hRS1 in Patients With X-linked Retinoschisis (XLRS)
A Phase 1/2 study testing rAAV2tYF-CB-hRS1 in people with X-linked Retinoschisis, run by Beacon Therapeutics at 9 sites in United States.
Trial summary
This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector expressing retinoschisin (rAAV2tYF-CB-hRS1) in patients with X-linked retinoschisis. Up to 27 participants will be enrolled and 3 dose levels will be evaluated in a dose escalation format. Read more about this study
- Who is it for?
- Ages 6 years and older, men only
- Conditions the study is for
- X-linked Retinoschisis
- What is being tested?
- rAAV2tYF-CB-hRS1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 9 sitesUnited States
- Study dates
- May 2015to 9 May 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Retinal disease consistent with a diagnosis of XLRS and documented mutations in the RS1 gene
- Male individual at least 18 years of age (dose escalation phase) or at least 6 years of age (maximum tolerated dose phase),
- Able to perform tests of visual and retinal function,
- Visual acuity specified for each group
- Not treated with CAIs currently or within 3 months prior to study enrollment,
- Have acceptable laboratory parameters.
Who cannot join
- Prior receipt of any AAV gene therapy product,
- Pre-existing eye conditions that would preclude the planned intravitreal injection or interfere with interpretation of study endpoints or complications of vector administration.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Michigan Kellogg Eye Center
Ann Arbor, Michigan, 48105
The Wilmer Eye Institute, Johns Hopkins Hospital
Baltimore, Maryland, 21287
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
Retina Foundation of the Southwest
Dallas, Texas, 75231
Duke Eye Center, Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine, Alkek Eye Center
Houston, Texas, 77030
University of Miami - Miller School of Medicine Bascom Palmer Eye Institute
Miami, Florida, 33136
Casey Eye Institute, Oregon Health and Sciences University
Portland, Oregon, 97239
University of California San Francisco, Dept. of Ophthalmology
San Francisco, California, 94143
About this study
Official title: A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing Retinoschisin (rAAV2tYF-CB-hRS1) in Patients With X-linked Retinoschisis
This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector expressing retinoschisin (rAAV2tYF-CB-hRS1) in patients with X-linked retinoschisis. Up to 27 participants will be enrolled and 3 dose levels will be evaluated in a dose escalation format.
Read the detailed description
This will be a non-randomized, open label, Phase 1/2 dose escalation study.
Up to 27 participants will be enrolled. Each participant will receive the study agent by intravitreal injection in one eye on a single occasion. Enrollment will begin with the lowest dose and will proceed to higher doses only after review of safety data by a Data and Safety Monitoring Committee (DSMC). Participants in the dose escalation phase will be ≥ 18 years of age. After the maximum tolerated dose is identified individuals ≥ 6 years of age will be enrolled.
Safety will be measured by the number and proportion of participants experiencing adverse events and immune response to RS1. Efficacy will be measured by evaluation of changes in visual function and schisis cavity size.
- Conditions
- X-linked Retinoschisis
- Being tested
- rAAV2tYF-CB-hRS1
- Keywords
- XLRS, maculoschisis, retinal degeneration, RS1, adeno-associated virus, gene therapy, AAV
- Medical subject headings
- Retinoschisis, Retinal Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAV2tYF-CB-hRS1Biological
adeno-associated virus vector expressing retinoschisin
| Study group | Role | What they receive |
|---|---|---|
| Groups 1A and 1B | Experimental | Subjects at least 18 y/o treated with a lower dose of rAAV2tYF-CB-hRS1 study drug. Receives: Biological: rAAV2tYF-CB-hRS1 |
| Groups 2 and 2A | Experimental | Subjects at least 6 y/o treated with a middle dose of rAAV2tYF-CB-hRS1 study drug. Receives: Biological: rAAV2tYF-CB-hRS1 |
| Group 3 | Experimental | Subjects at least 18 y/o treated with a higher dose of rAAV2tYF-CB-hRS1 study drug. Receives: Biological: rAAV2tYF-CB-hRS1 |
| Group 4 | Experimental | Subjects at least 6 y/o treated with a maximum tolerated dose of rAAV2tYF-CB-hRS1 study drug determined for Groups 1A, 1B, 2 and 3. Receives: Biological: rAAV2tYF-CB-hRS1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Adverse Events
Number of participants with ocular adverse events, assessed by standard ophthalmic examination, including slit lamp biomicroscopy, tonometry, and indirect ophthalmoscopy.
Measured: From Day 0 to Month 12 (12 months)
Secondary outcomes (3)
Change From Baseline in Best Corrected Visual Acuity (BCVA)
Change in ETDRS (Early Treatment of Diabetic Retinopathy) Letter Score. Minimum value=0; Maximum value=100. Higher scores indicate better visual acuity. Change = 12 Mo value - Baseline value
Measured: From Day 0 to Month 12 (12 Months)
Change From Baseline in Schisis Cavity Size on Optical Coherence Tomography (OCT)
Change in cystic cavity volume (mm^3), obtained from spectral domain optical coherence tomography (SD-OCT) of the retina, yielding volumetric measures of schisis cavity size and total cyst cavity. Change = 12 Mo value - Baseline value
Measured: From Day 0 to Month 12 (12 months)
Change From Baseline in B-wave Amplitude in Electroretinogram (ERG) Responses
Change in dark-adapted 3.0 B-wave amplitude (μV). Change = 12 Mo value - Baseline value
Measured: From Day 0 to Month 12 (12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2015 (estimated)
- Study startMay 2015
- Primary completionApr 2019
- Study completion9 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for X-linked RetinoschisisStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beacon Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Theresa Heah, MD, Study director, Applied Genetics Technologies Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02416622
- Sponsor's protocol ID
- AGTC-RS1-001
- Status last verified
- Jun 2023
- First submitted
- 2 Apr 2015
- Last updated
- 12 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Molday RS, Kellner U, Weber BH. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms. Prog Retin Eye Res. 2012 May;31(3):195-212. doi: 10.1016/j.preteyeres.2011.12.002. Epub 2012 Jan 3.
PubMed 22245536
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing Retinoschisin (rAAV2tYF-CB-hRS1) in Patients With X-linked Retinoschisis
- ClinicalTrials.gov ID
- NCT02416622
- Acronym / sponsor ID
- AGTC-RS1-001
- Conditions
- X-linked Retinoschisis
- Keywords
- XLRS, maculoschisis, retinal degeneration, RS1, adeno-associated virus, gene therapy, AAV
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Beacon TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- May 2015 (actual)
- Primary completion
- Apr 2019 (actual)
- Study completion
- 9 May 2023 (actual)
- First posted
- 15 Apr 2015 (estimated)
- Results
- Posted 1 Jul 2020
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 expressing retinoschisin (rAAV2tYF-CB-hRS1) in patients with X-linked retinoschisis. Up to 27 participants will be enrolled and 3 dose levels will be evaluated in a dose escalation format.
Detailed description
This will be a non-randomized, open label, Phase 1/2 dose escalation study.
Up to 27 participants will be enrolled. Each participant will receive the study agent by intravitreal injection in one eye on a single occasion. Enrollment will begin with the lowest dose and will proceed to higher doses only after review of safety data by a Data and Safety Monitoring Committee (DSMC). Participants in the dose escalation phase will be ≥ 18 years of age. After the maximum tolerated dose is identified individuals ≥ 6 years of age will be enrolled.
Safety will be measured by the number and proportion of participants experiencing adverse events and immune response to RS1. Efficacy will be measured by evaluation of changes in visual function and schisis cavity size.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Groups 1A and 1B | Experimental | Biological: rAAV2tYF-CB-hRS1Subjects at least 18 y/o treated with a lower dose of rAAV2tYF-CB-hRS1 study drug. |
| Groups 2 and 2A | Experimental | Biological: rAAV2tYF-CB-hRS1Subjects at least 6 y/o treated with a middle dose of rAAV2tYF-CB-hRS1 study drug. |
| Group 3 | Experimental | Biological: rAAV2tYF-CB-hRS1Subjects at least 18 y/o treated with a higher dose of rAAV2tYF-CB-hRS1 study drug. |
| Group 4 | Experimental | Biological: rAAV2tYF-CB-hRS1Subjects at least 6 y/o treated with a maximum tolerated dose of rAAV2tYF-CB-hRS1 study drug determined for Groups 1A, 1B, 2 and 3. |
Who may qualify
- Ages
- 6 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Retinal disease consistent with a diagnosis of XLRS and documented mutations in the RS1 gene
- Male individual at least 18 years of age (dose escalation phase) or at least 6 years of age (maximum tolerated dose phase),
- Able to perform tests of visual and retinal function,
- Visual acuity specified for each group
- Not treated with CAIs currently or within 3 months prior to study enrollment,
Key exclusion criteria (2 listed)
- Prior receipt of any AAV gene therapy product,
- Pre-existing eye conditions that would preclude the planned intravitreal injection or interfere with interpretation of study endpoints or complications of vector administration.
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-CB-hRS1adeno-associated virus vector expressing retinoschisin | Biological | Group 3, Group 4, Groups 1A and 1B, Groups 2 and 2A |
Primary outcome
Number of Participants Experiencing Adverse Events
Time frame: From Day 0 to Month 12 (12 months)
Number of participants with ocular adverse events, assessed by standard ophthalmic examination, including slit lamp biomicroscopy, tonometry, and indirect ophthalmoscopy.
3 secondary outcomes
Change From Baseline in Best Corrected Visual Acuity (BCVA)
Time frame: From Day 0 to Month 12 (12 Months)
Change From Baseline in Schisis Cavity Size on Optical Coherence Tomography (OCT)
Time frame: From Day 0 to Month 12 (12 months)
Change From Baseline in B-wave Amplitude in Electroretinogram (ERG) Responses
Time frame: From Day 0 to Month 12 (12 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22245536Molday RS, Kellner U, Weber BH. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms. Prog Retin Eye Res. 2012 May;31(3):195-212. doi: 10.1016/j.preteyeres.2011.12.002. Epub 2012 Jan 3.
- AGTC websiteLink provided by the sponsor.
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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.
Theresa Heah, MD study director
Applied Genetics Technologies Corporation
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rAAV2tYF-CB-hRS1 in people with X-linked Retinoschisis, run by Beacon Therapeutics at 9 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 6 inclusion and 2 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: finished, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 1 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Experiencing Adverse Events (time frame: From Day 0 to Month 12 (12 months)). 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 NCT02416622, 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 Jun 2023.