Retinal DegenerationPhase 1/2NCT00643747
Safety Study of RPE65 Gene Therapy to Treat Leber Congenital Amaurosis
A Phase 1/2 study testing tgAAG76 (rAAV 2/2.hRPE65p.hRPE65) in people with Retinal Degeneration, run by University College, London at 1 site in United Kingdom.
Trial summary
The purpose of the study is to determine whether gene therapy is safe and effective for the treatment of severe childhood blindness caused by mutations in RPE65. Read more about this study
- Who is it for?
- Ages 5 to 30 years
- Conditions the study is for
- Retinal Degeneration
- What is being tested?
- tgAAG76 (rAAV 2/2.hRPE65p.hRPE65)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2007to Dec 2014
- 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 5 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Clinical diagnosis of severe early-onset retinal dystrophy confirmed missense mutation(s) in RPE65
Who cannot join
- Visual acuity in the study eye better than 6/36 Snellen
- Hypertension
- Diabetes mellitus
- Tuberculosis
- Renal impairment
- Immunocompromise
Show all 10Show fewer
- Osteoporosis
- Gastric ulceration
- Severe affective disorder)
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Moorfields Eye Hospital NHS Foundation Trust
London, EC1V 2PD
About this study
Official title: An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (AAV2/2-hRPE65p-hRPE65) for Gene Therapy of Severe Early-onset Retinal Degeneration
The purpose of the study is to determine whether gene therapy is safe and effective for the treatment of severe childhood blindness caused by mutations in RPE65.
Read the detailed description
The main objective of the proposed trial is to determine the safety and efficacy subretinal administration of a recombinant adeno-associated viral vector (rAAV 2/2.hRPE65p.hRPE65) at three different dosage levels in individuals with autosomal recessive severe early-onset retinal degeneration due to mutations in RPE65. We have a comprehensive clinical monitoring plan to investigate the safety and efficacy of vector delivery.
- Conditions
- Retinal Degeneration
- Being tested
- tgAAG76 (rAAV 2/2.hRPE65p.hRPE65)
- Keywords
- retinal dystrophy, Leber congenital amaurosis, RPE65, gene therapy
- Medical subject headings
- Retinal Degeneration, Retinal Dystrophies, Leber Congenital Amaurosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tgAAG76 (rAAV 2/2.hRPE65p.hRPE65)Biological
Also called rAAV 2/2.hRPE65p.hRPE65
Single subretinal injection of vector suspension; up to 3x10e12 vector particles
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Injection of vector Receives: Biological: tgAAG76 (rAAV 2/2.hRPE65p.hRPE65) |
What is being measured
The primary outcome is the main question the study is designed to answer.
intraocular inflammation
Measured: at intervals up to 12 months
Secondary outcomes (1)
visual function
Measured: intervals up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2008 (estimated)
- Study startJan 2007
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Retinal DegenerationStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Moorfields Eye Hospital NHS Foundation Trust, Targeted Genetics Corporation
- Responsible party
- Sponsor
- Investigators
- Robin R Ali, PhD, Study director, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00643747
- Sponsor's protocol ID
- 06/061
- Status last verified
- Dec 2013
- First submitted
- 20 Mar 2008
- Last updated
- 7 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bainbridge JW, Mehat MS, Sundaram V, Robbie SJ, Barker SE, Ripamonti C, Georgiadis A, Mowat FM, Beattie SG, Gardner PJ, Feathers KL, Luong VA, Yzer S, Balaggan K, Viswanathan A, de Ravel TJ, Casteels I, Holder GE, Tyler N, Fitzke FW, Weleber RG, Nardini M, Moore AT, Thompson DA, Petersen-Jones SM, Michaelides M, van den Born LI, Stockman A, Smith AJ, Rubin G, Ali RR. Long-term effect of gene therapy on Leber's congenital amaurosis. N Engl J Med. 2015 May 14;372(20):1887-97. doi: 10.1056/NEJMoa1414221. Epub 2015 May 4.
PubMed 25938638Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2231-9. doi: 10.1056/NEJMoa0802268. Epub 2008 Apr 27.
PubMed 18441371Ripamonti C, Henning GB, Robbie SJ, Sundaram V, van den Born LI, Casteels I, de Ravel TJ, Moore AT, Smith AJ, Bainbridge JW, Ali RR, Stockman A. Spectral sensitivity measurements reveal partial success in restoring missing rod function with gene therapy. J Vis. 2015;15(15):20. doi: 10.1167/15.15.20.
PubMed 26605849
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (AAV2/2-hRPE65p-hRPE65) for Gene Therapy of Severe Early-onset Retinal Degeneration
- ClinicalTrials.gov ID
- NCT00643747
- Acronym / sponsor ID
- 06/061
- Conditions
- Retinal Degeneration
- Keywords
- retinal dystrophy, Leber congenital amaurosis, RPE65, gene therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Moorfields Eye Hospital NHS Foundation Trust, Targeted Genetics Corporation
- Study start
- Jan 2007
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 26 Mar 2008 (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.
The purpose of the study is to determine whether gene therapy is safe and effective for the treatment of severe childhood blindness caused by mutations in RPE65.
Detailed description
The main objective of the proposed trial is to determine the safety and efficacy subretinal administration of a recombinant adeno-associated viral vector (rAAV 2/2.hRPE65p.hRPE65) at three different dosage levels in individuals with autosomal recessive severe early-onset retinal degeneration due to mutations in RPE65. We have a comprehensive clinical monitoring plan to investigate the safety and efficacy of vector delivery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Biological: tgAAG76 (rAAV 2/2.hRPE65p.hRPE65)Injection of vector |
Who may qualify
- Ages
- 5 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Clinical diagnosis of severe early-onset retinal dystrophy confirmed missense mutation(s) in RPE65
Key exclusion criteria (10 listed)
- Visual acuity in the study eye better than 6/36 Snellen
- Hypertension
- Diabetes mellitus
- Tuberculosis
- Renal impairment
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 |
|---|---|---|
| tgAAG76 (rAAV 2/2.hRPE65p.hRPE65)Also: rAAV 2/2.hRPE65p.hRPE65Single subretinal injection of vector suspension; up to 3x10e12 vector particles | Biological | A |
Primary outcome
intraocular inflammation
Time frame: at intervals up to 12 months
1 secondary outcome
visual function
Time frame: intervals up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2015.
- Background: PubMed 25938638Bainbridge JW, Mehat MS, Sundaram V, Robbie SJ, Barker SE, Ripamonti C, Georgiadis A, Mowat FM, Beattie SG, Gardner PJ, Feathers KL, Luong VA, Yzer S, Balaggan K, Viswanathan A, de Ravel TJ, Casteels I, Holder GE, Tyler N, Fitzke FW, Weleber RG, Nardini M, Moore AT, Thompson DA, Petersen-Jones SM, Michaelides M, van den Born LI, Stockman A, Smith AJ, Rubin G, Ali RR. Long-term effect of gene therapy on Leber's congenital amaurosis. N Engl J Med. 2015 May 14;372(20):1887-97. doi: 10.1056/NEJMoa1414221. Epub 2015 May 4.
- Results publication: PubMed 18441371Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2231-9. doi: 10.1056/NEJMoa0802268. Epub 2008 Apr 27.
- Derived from this study: PubMed 26605849Ripamonti C, Henning GB, Robbie SJ, Sundaram V, van den Born LI, Casteels I, de Ravel TJ, Moore AT, Smith AJ, Bainbridge JW, Ali RR, Stockman A. Spectral sensitivity measurements reveal partial success in restoring missing rod function with gene therapy. J Vis. 2015;15(15):20. doi: 10.1167/15.15.20.
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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.
Robin R Ali, PhD study director
University College, London
1 site 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 tgAAG76 (rAAV 2/2.hRPE65p.hRPE65) in people with Retinal Degeneration, run by University College, London at 1 site in United Kingdom.
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 1 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 7 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
intraocular inflammation (time frame: at intervals up to 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 NCT00643747, which also lists 3 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 7 Dec 2015.