Leber Congenital AmaurosisPhase 1/2NCT00749957
Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis
A Phase 1/2 study testing rAAV2-CB-hRPE65 in people with Leber Congenital Amaurosis, run by Beacon Therapeutics at 2 sites in United States.
Trial summary
The purpose of the study is to evaluate the safety and efficacy of an adeno-associated virus vector expressing RPE65 in patients with Leber congenital amaurosis caused by mutations in the RPE65 gene. Funding Source - FDA OOPD Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Leber Congenital Amaurosis
- What is being tested?
- rAAV2-CB-hRPE65
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Jun 2009to 22 Sep 2017
- 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
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Retinal disease consistent with a diagnosis of Leber congenital amaurosis and documented mutations in the RPE65 gene (including null mutations and mutations that code for abnormal RPE65 protein);
- At least 6 years of age;
- Good general health without significant physical examination findings or clinically significant abnormal laboratory results;
- Able to perform tests of visual and retinal function;
- Visual acuity not better than 20/60 and not worse than hand motion in both the treated eye and the fellow eye;
- Visible photoreceptor (outer nuclear) layer on a standard optical coherence tomography (OCT) scan;
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- Acceptable hematology, clinical chemistry and urine laboratory parameters;
- For females of childbearing potential, a negative pregnancy test at screening and at baseline, and agreement to use effective contraception for 12 months after administration of rAAV2-CB-hRPE65, for sexual activity that could lead to pregnancy;
- For males of reproductive potential, agreement to use effective contraception for 12 months after administration of rAAV2-CB-hRPE65, for sexual activity that could lead to pregnancy
Who cannot join
- Pre-existing eye conditions that would preclude the planned surgery or interfere with interpretation of study endpoints or complications of surgery (e.g. glaucoma, corneal or lenticular opacities, or history or retinal detachment);
- Presence of epiretinal membrane on OCT;
- History of immunodeficiency or other medical conditions that might increase the risk of rAAV2-CB-hRPE65 administration;
- Use of anticoagulants or anti-platelet agents within 7 days prior to study agent administration;
- History of allergy or sensitivity to medications planned for use in the peri-operative period;
- For females of childbearing potential, a positive pregnancy test at screening or baseline (within 2 days before rAAV2-CB-hRPE65 administration);
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- Females who are breast feeding;
- Use of any investigational agent, or systemic corticosteroids or other immunosuppressive drug(s), within 3 months prior to enrollment;
- Prior receipt of any AAV gene therapy product;
- Any condition which leads the investigator to believe that the participant cannot comply with the protocol requirements or that may place the participant at an unacceptable risk for participation.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Casey Eye Institue, Oregon Health & Science University
Portland, Oregon, 97239
University of Massachusetts Medical School
Worcester, Massachusetts, 01605
About this study
Official title: A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing RPE65 (rAAV2-CB-hRPE65) in Patients With Leber Congenital Amaurosis Type 2
The purpose of the study is to evaluate the safety and efficacy of an adeno-associated virus vector expressing RPE65 in patients with Leber congenital amaurosis caused by mutations in the RPE65 gene.
Funding Source - FDA OOPD
Read the detailed description
This will be a non-randomized, open label study. A total of 12 participants will be enrolled into two groups of 6 each. Each participant will receive rAAV2 CB hRPE65 by subretinal injection in one eye on a single occasion. Participants in Group 1 will receive 450 µL at a dosage level of 4 x 10^11 vg/mL containing a total of 1.8 x 10^11 vg of rAAV2-CB-hRPE65. Participants in Group 2 will receive 450 µL at a dosage level of 1.33 x 10^12 vg/mL containing a total of 6 x 10^11 vg of rAAV2-CB-hRPE65. A retinal surgeon will administer the vector by subretinal injection.
Enrollment will begin with Group 1 and will proceed to Group 2 after review of safety data by a Data and Safety Monitoring Committee.
Safety will be monitored by evaluation of ocular and non ocular adverse events and hematology and clinical chemistry parameters. Efficacy will be measured by evaluation of visual fields, visual acuity and electroretinography.
- Conditions
- Leber Congenital Amaurosis
- Being tested
- rAAV2-CB-hRPE65
- Keywords
- AAV, adeno-associated virus, RPE65, Leber congenital amaurosis, LCA, gene therapy, human gene transfer
- Medical subject headings
- Leber Congenital Amaurosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAV2-CB-hRPE65Biological
Recombinant adeno-associated virus vector expressing RPE65
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Subjects at least 6 y/o treated with a lower dose of the vector by subretinal injection Receives: Biological: rAAV2-CB-hRPE65 |
| 2 | Experimental | Subjects at least 6 y/o treated with a higher dose of the vector by subretinal injection Receives: Biological: rAAV2-CB-hRPE65 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Ocular or Non-ocular Adverse Events
Measured: 2 years
Secondary outcomes (2)
Participants With Changes in Visual Fields
Improvement in the central 30 degree visual field, measured by static perimetry, at one or more time points after treatment, that was greater than the limit of agreement for baseline values .
Measured: 2 years
Participants With Changes in Best Corrected Visual Acuity
Increase in BCVA of 7 or more letters at Year 2 visit compared to average baseline value
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2008 (estimated)
- Study start17 Jun 2009
- Primary completion23 Sep 2014
- Study completion22 Sep 2017
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 (5)Papers the sponsor has linked to this study.
- Other trials for Leber Congenital AmaurosisStudies 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beacon Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- J Timothy Stout, MD, PhD, MBA, Principal investigator, Casey Eye Institute, Oregon Health & Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00749957
- Sponsor's protocol ID
- AGTC-RPE65-002
- Other IDs
- R01FD003694
- Status last verified
- Oct 2017
- First submitted
- 8 Sep 2008
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Acland GM, Aguirre GD, Bennett J, Aleman TS, Cideciyan AV, Bennicelli J, Dejneka NS, Pearce-Kelling SE, Maguire AM, Palczewski K, Hauswirth WW, Jacobson SG. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther. 2005 Dec;12(6):1072-82. doi: 10.1016/j.ymthe.2005.08.008. Epub 2005 Oct 14.
PubMed 16226919Jacobson SG, Boye SL, Aleman TS, Conlon TJ, Zeiss CJ, Roman AJ, Cideciyan AV, Schwartz SB, Komaromy AM, Doobrajh M, Cheung AY, Sumaroka A, Pearce-Kelling SE, Aguirre GD, Kaushal S, Maguire AM, Flotte TR, Hauswirth WW. Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis. Hum Gene Ther. 2006 Aug;17(8):845-58. doi: 10.1089/hum.2006.17.845.
PubMed 16942444Weleber RG, Pennesi ME, Wilson DJ, Kaushal S, Erker LR, Jensen L, McBride MT, Flotte TR, Humphries M, Calcedo R, Hauswirth WW, Chulay JD, Stout JT. Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. Ophthalmology. 2016 Jul;123(7):1606-20. doi: 10.1016/j.ophtha.2016.03.003. Epub 2016 Apr 19.
PubMed 27102010Ku CA, Igelman AD, Huang SJ, Bailey ST, Lauer AK, Duncan JL, Weleber RG, Yang P, Pennesi ME. Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector. Transl Vis Sci Technol. 2024 Jun 3;13(6):11. doi: 10.1167/tvst.13.6.11.
PubMed 38888288Pennesi ME, Weleber RG, Yang P, Whitebirch C, Thean B, Flotte TR, Humphries M, Chegarnov E, Beasley KN, Stout JT, Chulay JD. Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy. Hum Gene Ther. 2018 Dec;29(12):1428-1437. doi: 10.1089/hum.2018.014. Epub 2018 Jul 24.
PubMed 29869534
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. 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 RPE65 (rAAV2-CB-hRPE65) in Patients With Leber Congenital Amaurosis Type 2
- ClinicalTrials.gov ID
- NCT00749957
- Acronym / sponsor ID
- AGTC-RPE65-002
- Conditions
- Leber Congenital Amaurosis
- Keywords
- AAV, adeno-associated virus, RPE65, Leber congenital amaurosis, LCA, gene therapy, human gene transfer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Beacon TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Oregon Health and Science University, University of Massachusetts, Worcester
- Study start
- 17 Jun 2009 (actual)
- Primary completion
- 23 Sep 2014 (actual)
- Study completion
- 22 Sep 2017 (actual)
- First posted
- 10 Sep 2008 (estimated)
- Results
- Posted 8 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate the safety and efficacy of an adeno-associated virus vector expressing RPE65 in patients with Leber congenital amaurosis caused by mutations in the RPE65 gene.
Funding Source - FDA OOPD
Detailed description
This will be a non-randomized, open label study. A total of 12 participants will be enrolled into two groups of 6 each. Each participant will receive rAAV2 CB hRPE65 by subretinal injection in one eye on a single occasion. Participants in Group 1 will receive 450 µL at a dosage level of 4 x 10^11 vg/mL containing a total of 1.8 x 10^11 vg of rAAV2-CB-hRPE65. Participants in Group 2 will receive 450 µL at a dosage level of 1.33 x 10^12 vg/mL containing a total of 6 x 10^11 vg of rAAV2-CB-hRPE65. A retinal surgeon will administer the vector by subretinal injection.
Enrollment will begin with Group 1 and will proceed to Group 2 after review of safety data by a Data and Safety Monitoring Committee.
Safety will be monitored by evaluation of ocular and non ocular adverse events and hematology and clinical chemistry parameters. Efficacy will be measured by evaluation of visual fields, visual acuity and electroretinography.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: rAAV2-CB-hRPE65Subjects at least 6 y/o treated with a lower dose of the vector by subretinal injection |
| 2 | Experimental | Biological: rAAV2-CB-hRPE65Subjects at least 6 y/o treated with a higher dose of the vector by subretinal injection |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Retinal disease consistent with a diagnosis of Leber congenital amaurosis and documented mutations in the RPE65 gene (including null mutations and mutations that code for abnormal RPE65 protein);
- At least 6 years of age;
- Good general health without significant physical examination findings or clinically significant abnormal laboratory results;
- Able to perform tests of visual and retinal function;
- Visual acuity not better than 20/60 and not worse than hand motion in both the treated eye and the fellow eye;
Key exclusion criteria (10 listed)
- Pre-existing eye conditions that would preclude the planned surgery or interfere with interpretation of study endpoints or complications of surgery (e.g. glaucoma, corneal or lenticular opacities, or history or retinal detachment);
- Presence of epiretinal membrane on OCT;
- History of immunodeficiency or other medical conditions that might increase the risk of rAAV2-CB-hRPE65 administration;
- Use of anticoagulants or anti-platelet agents within 7 days prior to study agent administration;
- History of allergy or sensitivity to medications planned for use in the peri-operative period;
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 |
|---|---|---|
| rAAV2-CB-hRPE65Recombinant adeno-associated virus vector expressing RPE65 | Biological | 1, 2 |
Primary outcome
Number of Participants Experiencing Ocular or Non-ocular Adverse Events
Time frame: 2 years
2 secondary outcomes
Participants With Changes in Visual Fields
Time frame: 2 years
Participants With Changes in Best Corrected Visual Acuity
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16226919Acland GM, Aguirre GD, Bennett J, Aleman TS, Cideciyan AV, Bennicelli J, Dejneka NS, Pearce-Kelling SE, Maguire AM, Palczewski K, Hauswirth WW, Jacobson SG. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther. 2005 Dec;12(6):1072-82. doi: 10.1016/j.ymthe.2005.08.008. Epub 2005 Oct 14.
- Background: PubMed 16942444Jacobson SG, Boye SL, Aleman TS, Conlon TJ, Zeiss CJ, Roman AJ, Cideciyan AV, Schwartz SB, Komaromy AM, Doobrajh M, Cheung AY, Sumaroka A, Pearce-Kelling SE, Aguirre GD, Kaushal S, Maguire AM, Flotte TR, Hauswirth WW. Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis. Hum Gene Ther. 2006 Aug;17(8):845-58. doi: 10.1089/hum.2006.17.845.
- Background: PubMed 27102010Weleber RG, Pennesi ME, Wilson DJ, Kaushal S, Erker LR, Jensen L, McBride MT, Flotte TR, Humphries M, Calcedo R, Hauswirth WW, Chulay JD, Stout JT. Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. Ophthalmology. 2016 Jul;123(7):1606-20. doi: 10.1016/j.ophtha.2016.03.003. Epub 2016 Apr 19.
- Derived from this study: PubMed 38888288Ku CA, Igelman AD, Huang SJ, Bailey ST, Lauer AK, Duncan JL, Weleber RG, Yang P, Pennesi ME. Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector. Transl Vis Sci Technol. 2024 Jun 3;13(6):11. doi: 10.1167/tvst.13.6.11.
- Derived from this study: PubMed 29869534Pennesi ME, Weleber RG, Yang P, Whitebirch C, Thean B, Flotte TR, Humphries M, Chegarnov E, Beasley KN, Stout JT, Chulay JD. Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy. Hum Gene Ther. 2018 Dec;29(12):1428-1437. doi: 10.1089/hum.2018.014. Epub 2018 Jul 24.
- Applied Genetic Technologies Corporation home pageLink 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.
J Timothy Stout, MD, PhD, MBA principal investigator
Casey Eye Institute, Oregon Health & Science University
2 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 rAAV2-CB-hRPE65 in people with Leber Congenital Amaurosis, run by Beacon Therapeutics at 2 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 9 inclusion and 10 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 28 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 8 Apr 2016). 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 Ocular or Non-ocular Adverse Events (time frame: 2 years). 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 NCT00749957, which also lists 5 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 28 Dec 2017; AzTrials last refreshed its copy on 7 Nov 2026.