AchromatopsiaPhase 1/2NCT02599922
Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia (A Clarity Clinical Trial)
A Phase 1/2 study testing rAAV2tYF-PR1.7-hCNGB3 in people with Achromatopsia, run by Beacon Therapeutics at 8 sites in United States.
Trial summary
This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Achromatopsia
- What is being tested?
- rAAV2tYF-PR1.7-hCNGB3
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 8 sitesUnited States
- Study dates
- 11 Apr 2016to Jul 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female subjects with documented mutations in both alleles of the CNGB3 gene;
- Retinal disease consistent with a clinical diagnosis of achromatopsia;
- At least 18 years of age for Groups 1, 2, 3, 4, 5 and 6. At least 6 years of age for Group 4a, and 4-8 years of age for Groups 5a and 7;
- Able to perform tests of visual and retinal function;
- Visual acuity in the study eye not better than 55 ETDRS letters (Snellen equivalent 20/80) based on the average of two examinations at the baseline visit;
- Acceptable laboratory parameters;
- For females of childbearing potential: A negative pregnancy test within 2 days before administration of study agent.
Who cannot join
- Best-corrected visual acuity difference between the two eyes of > 15 ETDRS letters (3 lines);
- Evidence of degenerative myopia in the study eye;
- Pre-existing eye conditions that would contribute to vision loss in either eye or increase the risk of subretinal injection in the study eye.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
Boston Children's Hospital
Boston, Massachusetts, 02115
Pangere Center for Inherited Retinal Diseases, The Chicago Lighthouse for People Who Are Blind or Visually Imp
Chicago, Illinois, 60608
Cincinnati Eye Institute
Cincinnati, Ohio, 45242
Duke Eye Center, Duke University Medical Center
Durham, North Carolina, 27710
VitreoRetinal Associates
Gainesville, Florida, 32607
Bascom Palmer Eye Institute
Miami, Florida, 33136
Casey Eye Institute, Oregon Health and Sciences University
Portland, Oregon, 97239
About this study
Official title: A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing CNGB3 in Patients With Congenital Achromatopsia Caused by Mutations in the CNGB3 Gene
This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.
Read the detailed description
This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.
Subjects will be enrolled sequentially in seven dosing groups. Subjects in Groups 1, 2, 3, 4, 5, and 6 will be at least 18 years of age and will receive varying dose levels of study agent. Subjects in Group 4a will be 6 to 17 years of age and will receive the same dose as Group 4. Subjects in Groups 5a and 7 will be between 4 and 8 years of age. Subjects in Group 5a will receive the same dose as Group 5, and subjects in Group 7 will receive the maximum tolerated dose identified in Groups 1, 2, 3, 4, 4a, 5, 5a, and 6.
Safety will be monitored by evaluation of ocular and non-ocular adverse events and hematology and clinical chemistry parameters. Efficacy parameters will include visual acuity, light discomfort testing, color vision, static visual field, ERG, adaptive optics retinal imaging, functional MRI (fMRI), color brightness test and OCT.
- Conditions
- Achromatopsia
- Being tested
- rAAV2tYF-PR1.7-hCNGB3
- Medical subject headings
- Color Vision Defects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAV2tYF-PR1.7-hCNGB3Biological
Also called AGTC-401
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: 2.0 x 10^11 vg/mL of AGTC-401 | Experimental | Subjects at least 18 y/o treated with 2.0 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Receives: Biological: rAAV2tYF-PR1.7-hCNGB3 |
| Group 2: 4.0 x 10^10 vg/mL of AGTC-401 | Experimental | Subjects at least 18 y/o treated with 4.0 x 10^10 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Receives: Biological: rAAV2tYF-PR1.7-hCNGB3 |
| Group 3: 1.2 x 10^11 vg/mL of AGTC-401 | Experimental | Subjects at least 18 y/o treated with 1.2 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Receives: Biological: rAAV2tYF-PR1.7-hCNGB3 |
| Group 4: 3.6 x 10^11 vg/mL of AGTC-401 | Experimental | Subjects at least 18 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Receives: Biological: rAAV2tYF-PR1.7-hCNGB3 |
| Group 4a: 3.6 x 10^11 vg/mL of AGTC-401 | Experimental | Subjects 6 to 17 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Receives: Biological: rAAV2tYF-PR1.7-hCNGB3 |
| Group 5: 1.1 x 10^12 vg/mL of AGTC-401 | Experimental | Subjects at least 18 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Receives: Biological: rAAV2tYF-PR1.7-hCNGB3 |
| Group 5a: 1.1 x 10^12 vg/mL of AGTC-401 | Experimental | Subjects 4 to 8 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Receives: Biological: rAAV2tYF-PR1.7-hCNGB3 |
| Group 6: 3.2 x 10^12 vg/mL of AGTC-401 | Experimental | Subjects at least 18 y/o treated with 3.2 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Receives: Biological: rAAV2tYF-PR1.7-hCNGB3 |
| Group 7: MTD of AGTC-401 | Experimental | Subjects 4 to 8 y/o treated with a maximum tolerated dose of rAAV2tYF-PR1/7-hCNGB3 study drug determined by Groups 1-6. Receives: Biological: rAAV2tYF-PR1.7-hCNGB3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Proportion of participants experiencing grade 3 or greater adverse events
Measured: 1 year
Secondary outcomes (3)
Visual acuity
Changes in best corrected visual acuity compared to pre-treatment
Measured: 1 year
Light aversion
Changes in light discomfort testing compared to pre-treatment
Measured: 1 year
Color vision
Changes in color vision testing compared to pre-treatment
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2015 (estimated)
- Study start11 Apr 2016
- Primary completionJul 2022 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AchromatopsiaStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beacon Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Eye Institute (NEI)
- Responsible party
- Sponsor
- Investigators
- David Jacobs, MD, MBA, Study director, Applied Genetic Technologies Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02599922
- Sponsor's protocol ID
- AGTC_CNGB3-001
- Other IDs
- R24EY022023
- Status last verified
- Jul 2022
- First submitted
- 5 Nov 2015
- Last updated
- 22 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Komaromy AM, Alexander JJ, Rowlan JS, Garcia MM, Chiodo VA, Kaya A, Tanaka JC, Acland GM, Hauswirth WW, Aguirre GD. Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet. 2010 Jul 1;19(13):2581-93. doi: 10.1093/hmg/ddq136. Epub 2010 Apr 8.
PubMed 20378608Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.
PubMed 30194931
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2022. 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 CNGB3 in Patients With Congenital Achromatopsia Caused by Mutations in the CNGB3 Gene
- ClinicalTrials.gov ID
- NCT02599922
- Acronym / sponsor ID
- AGTC_CNGB3-001
- Conditions
- Achromatopsia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Beacon TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- National Eye Institute (NEI)
- Study start
- 11 Apr 2016 (actual)
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 9 Nov 2015 (estimated)
- 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 will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.
Detailed description
This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.
Subjects will be enrolled sequentially in seven dosing groups. Subjects in Groups 1, 2, 3, 4, 5, and 6 will be at least 18 years of age and will receive varying dose levels of study agent. Subjects in Group 4a will be 6 to 17 years of age and will receive the same dose as Group 4. Subjects in Groups 5a and 7 will be between 4 and 8 years of age. Subjects in Group 5a will receive the same dose as Group 5, and subjects in Group 7 will receive the maximum tolerated dose identified in Groups 1, 2, 3, 4, 4a, 5, 5a, and 6.
Safety will be monitored by evaluation of ocular and non-ocular adverse events and hematology and clinical chemistry parameters. Efficacy parameters will include visual acuity, light discomfort testing, color vision, static visual field, ERG, adaptive optics retinal imaging, functional MRI (fMRI), color brightness test and OCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Group 1: 2.0 x 10^11 vg/mL of AGTC-401 | Experimental | Biological: rAAV2tYF-PR1.7-hCNGB3Subjects at least 18 y/o treated with 2.0 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. |
| Group 2: 4.0 x 10^10 vg/mL of AGTC-401 | Experimental | Biological: rAAV2tYF-PR1.7-hCNGB3Subjects at least 18 y/o treated with 4.0 x 10^10 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. |
| Group 3: 1.2 x 10^11 vg/mL of AGTC-401 | Experimental | Biological: rAAV2tYF-PR1.7-hCNGB3Subjects at least 18 y/o treated with 1.2 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. |
| Group 4: 3.6 x 10^11 vg/mL of AGTC-401 | Experimental | Biological: rAAV2tYF-PR1.7-hCNGB3Subjects at least 18 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. |
| Group 4a: 3.6 x 10^11 vg/mL of AGTC-401 | Experimental | Biological: rAAV2tYF-PR1.7-hCNGB3Subjects 6 to 17 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. |
| Group 5: 1.1 x 10^12 vg/mL of AGTC-401 | Experimental | Biological: rAAV2tYF-PR1.7-hCNGB3Subjects at least 18 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. |
| Group 5a: 1.1 x 10^12 vg/mL of AGTC-401 | Experimental | Biological: rAAV2tYF-PR1.7-hCNGB3Subjects 4 to 8 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. |
| Group 6: 3.2 x 10^12 vg/mL of AGTC-401 | Experimental | Biological: rAAV2tYF-PR1.7-hCNGB3Subjects at least 18 y/o treated with 3.2 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. |
| Group 7: MTD of AGTC-401 | Experimental | Biological: rAAV2tYF-PR1.7-hCNGB3Subjects 4 to 8 y/o treated with a maximum tolerated dose of rAAV2tYF-PR1/7-hCNGB3 study drug determined by Groups 1-6. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female subjects with documented mutations in both alleles of the CNGB3 gene;
- Retinal disease consistent with a clinical diagnosis of achromatopsia;
- At least 18 years of age for Groups 1, 2, 3, 4, 5 and 6. At least 6 years of age for Group 4a, and 4-8 years of age for Groups 5a and 7;
- Able to perform tests of visual and retinal function;
- Visual acuity in the study eye not better than 55 ETDRS letters (Snellen equivalent 20/80) based on the average of two examinations at the baseline visit;
Key exclusion criteria (3 listed)
- Best-corrected visual acuity difference between the two eyes of > 15 ETDRS letters (3 lines);
- Evidence of degenerative myopia in the study eye;
- Pre-existing eye conditions that would contribute to vision loss in either eye or increase the risk of subretinal injection in the study eye.
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-PR1.7-hCNGB3Also: AGTC-401rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene. | Biological | Group 1: 2.0 x 10^11 vg/mL of AGTC-401, Group 2: 4.0 x 10^10 vg/mL of AGTC-401, Group 3: 1.2 x 10^11 vg/mL of AGTC-401, Group 4: 3.6 x 10^11 vg/mL of AGTC-401, Group 4a: 3.6 x 10^11 vg/mL of AGTC-401, Group 5: 1.1 x 10^12 vg/mL of AGTC-401, Group 5a: 1.1 x 10^12 vg/mL of AGTC-401, Group 6: 3.2 x 10^12 vg/mL of AGTC-401, Group 7: MTD of AGTC-401 |
Primary outcome
Adverse events
Time frame: 1 year
Proportion of participants experiencing grade 3 or greater adverse events
3 secondary outcomes
Visual acuity
Time frame: 1 year
Light aversion
Time frame: 1 year
Color vision
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2022.
- Background: PubMed 20378608Komaromy AM, Alexander JJ, Rowlan JS, Garcia MM, Chiodo VA, Kaya A, Tanaka JC, Acland GM, Hauswirth WW, Aguirre GD. Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet. 2010 Jul 1;19(13):2581-93. doi: 10.1093/hmg/ddq136. Epub 2010 Apr 8.
- Derived from this study: PubMed 30194931Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.
- Sponsor 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.
David Jacobs, MD, MBA study director
Applied Genetic Technologies Corporation
8 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-PR1.7-hCNGB3 in people with Achromatopsia, run by Beacon Therapeutics at 8 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 7 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 22 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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?
Results are not available in the source record.
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?
Adverse events (time frame: 1 year). 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 NCT02599922, which also lists 2 linked publications.
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 22 Jul 2022.