ChoroideremiaPhase 1/2NCT01461213
Gene Therapy for Blindness Caused by Choroideremia
A Phase 1/2 study testing rAAV2.REP1 in people with Choroideremia, run by University of Oxford at 4 sites in United Kingdom.
Trial summary
Primary objective: To assess the safety and tolerability of the AAV.REP1 vector, administered at two different doses to the retina in 12 patients with a diagnosis of choroideremia. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Choroideremia
- What is being tested?
- rAAV2.REP1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- Oct 2011to Oct 2017
- 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 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant is willing and able to give informed consent for participation in the study,
- Male aged 18 years or above,
- Diagnosed with choroideraemia and in good health,
- Active disease with SLO changes visible within the macula region,
- Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study,
- Vision at least 6/60 or better in the study eye.
Who cannot join
- Female and child participants (under the age of 18),
- Men unwilling to use barrier contraception methods, if relevant,
- Previous history of retinal surgery or ocular inflammatory disease (uveitis),
- Grossly asymmetrical disease or other ocular morbidity which might confound use of the fellow eye as a long-term control,
- Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study,
- Participants who have participated in another research study involving an investigational product in the previous 12 weeks.
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites
Moorfields Eye Hospital NHS Foundation Trust
London, EC1V 2PD
St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust
Manchester, M13 9WL
Oxford Radcliffe Hospitals NHS Trust
Oxford, OX3 9DU
Eye Unit, Southampton University Hospitals NHS Trust
Southampton, SO16 6YD
About this study
Official title: An Open Label Dose Escalation Phase 1 Clinical Trial of Retinal Gene Therapy for Choroideraemia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1)
- Primary objective: To assess the safety and tolerability of the AAV.REP1 vector, administered at two different doses to the retina in 12 patients with a diagnosis of choroideremia.
- Secondary Objective: To identify any therapeutic benefit as evidenced by a slowing down of the retinal degeneration assessed by functional and anatomical methods in the treated eye compared to the control eye 24 months after gene delivery.
Read the detailed description
Detailed description may be found in the following scientific publication:
Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial, The Lancet, Volume 383, Issue 9923, Pages 1129 - 1137 (29 March 2014).
Links: www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62117-0/abstract ; http://dx.doi.org/doi:10.1016/S0140-6736(13)62117-0
- Conditions
- Choroideremia
- Being tested
- rAAV2.REP1
- Keywords
- Tapetoretinal degeneration, choroideraemia, X-linked, retinitis pigmentosa
- Medical subject headings
- Choroideremia, Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAV2.REP1Drug
Also called Adeno-associated viral vector
Single subretinal injection of rAAV2.REP1 vector suspension containing 10e12 genome particles per ml. Dose 1 = dose containing approximately 10e10 rAAV2.REP1 genome particles. Dose 2 = dose containing approximately 10e11 rAAV2.REP1 genome particles.
| Study group | Role | What they receive |
|---|---|---|
| Dose 1 | Experimental | Dose 1 = single subretinal injection of vector suspension containing approximately 10e10 rAAV2.REP1 genome particles. Six patients have now received Dose 1. Receives: Drug: rAAV2.REP1 |
| Dose 2 | Experimental | Dose 2 = single subretinal injection of vector suspension containing approximately 10e11 rAAV2.REP1 genome particles. Three patients thus far have received Dose 2. Receives: Drug: rAAV2.REP1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual acuity
Best corrected visual acuity, following cataract surgery if indicated
Measured: 6 months
Secondary outcomes (1)
Microperimetry, OCT and fundus autofluorescence
Structure function correlations at the margins of the retinal degeneration
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionOct 2017
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ChoroideremiaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Oxford University Hospitals NHS Trust, Moorfields Eye Hospital NHS Foundation Trust, University College, London, Manchester University NHS Foundation Trust, University of Manchester, University Hospital Southampton NHS Foundation Trust, University of Southampton
- Responsible party
- Sponsor
- Investigators
- Robert E MacLaren, MB ChB DPhil, Study chair, University of Oxford, Oxford Radcliffe Hospitals NHS Trust and Moorfields Eye HospitalMiguel C Seabra, MD PhD, Principal investigator, Imperial College LondonAndrew R Webster, MD, Principal investigator, UCL Institute of Ophthalmology and Moorfields Eye HospitalSusan M Downes, MD, Principal investigator, Oxford University Hospitals NHS TrustGraeme C Black, MB BCh DPhil, Principal investigator, University of Manchester and Central Manchester University Hospitals NHS Foundation TrustAndrew J Lotery, MD, Principal investigator, University of Southampton and Southampton University Hospitals TrustLen W Seymour, PhD, Principal investigator, University of OxfordTanya Tolmachova, PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01461213
- Sponsor's protocol ID
- CHM09/01
- Other IDs
- 2009-014617-27, 2009
- Status last verified
- Nov 2017
- First submitted
- 21 Oct 2011
- Last updated
- 17 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Simunovic MP, Jolly JK, Xue K, Edwards TL, Groppe M, Downes SM, MacLaren RE. The Spectrum of CHM Gene Mutations in Choroideremia and Their Relationship to Clinical Phenotype. Invest Ophthalmol Vis Sci. 2016 Nov 1;57(14):6033-6039. doi: 10.1167/iovs.16-20230.
PubMed 27820636Xue K, Oldani M, Jolly JK, Edwards TL, Groppe M, Downes SM, MacLaren RE. Correlation of Optical Coherence Tomography and Autofluorescence in the Outer Retina and Choroid of Patients With Choroideremia. Invest Ophthalmol Vis Sci. 2016 Jul 1;57(8):3674-84. doi: 10.1167/iovs.15-18364.
PubMed 27403996Seitz IP, Zhour A, Kohl S, Llavona P, Peter T, Wilhelm B, Zrenner E, Ueffing M, Bartz-Schmidt KU, Fischer MD. Multimodal assessment of choroideremia patients defines pre-treatment characteristics. Graefes Arch Clin Exp Ophthalmol. 2015 Dec;253(12):2143-50. doi: 10.1007/s00417-015-2976-4. Epub 2015 Mar 7.
PubMed 25744334MacLaren RE, Groppe M, Barnard AR, Cottriall CL, Tolmachova T, Seymour L, Clark KR, During MJ, Cremers FP, Black GC, Lotery AJ, Downes SM, Webster AR, Seabra MC. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. 2014 Mar 29;383(9923):1129-37. doi: 10.1016/S0140-6736(13)62117-0. Epub 2014 Jan 16.
PubMed 24439297
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Dose Escalation Phase 1 Clinical Trial of Retinal Gene Therapy for Choroideraemia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1)
- ClinicalTrials.gov ID
- NCT01461213
- Acronym / sponsor ID
- CHM09/01
- Conditions
- Choroideremia
- Keywords
- Tapetoretinal degeneration, choroideraemia, X-linked, retinitis pigmentosa
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Oxford University Hospitals NHS Trust, Moorfields Eye Hospital NHS Foundation Trust, University College, London, Manchester University NHS Foundation Trust, University of Manchester, University Hospital Southampton NHS Foundation Trust, University of Southampton
- Study start
- Oct 2011
- Primary completion
- Oct 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 28 Oct 2011 (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.
- Primary objective: To assess the safety and tolerability of the AAV.REP1 vector, administered at two different doses to the retina in 12 patients with a diagnosis of choroideremia.
- Secondary Objective: To identify any therapeutic benefit as evidenced by a slowing down of the retinal degeneration assessed by functional and anatomical methods in the treated eye compared to the control eye 24 months after gene delivery.
Detailed description
Detailed description may be found in the following scientific publication:
Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial, The Lancet, Volume 383, Issue 9923, Pages 1129 - 1137 (29 March 2014).
Links: www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62117-0/abstract ; http://dx.doi.org/doi:10.1016/S0140-6736(13)62117-0
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose 1 | Experimental | Drug: rAAV2.REP1Dose 1 = single subretinal injection of vector suspension containing approximately 10e10 rAAV2.REP1 genome particles. Six patients have now received Dose 1. |
| Dose 2 | Experimental | Drug: rAAV2.REP1Dose 2 = single subretinal injection of vector suspension containing approximately 10e11 rAAV2.REP1 genome particles. Three patients thus far have received Dose 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participant is willing and able to give informed consent for participation in the study,
- Male aged 18 years or above,
- Diagnosed with choroideraemia and in good health,
- Active disease with SLO changes visible within the macula region,
- Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study,
Key exclusion criteria (6 listed)
- Female and child participants (under the age of 18),
- Men unwilling to use barrier contraception methods, if relevant,
- Previous history of retinal surgery or ocular inflammatory disease (uveitis),
- Grossly asymmetrical disease or other ocular morbidity which might confound use of the fellow eye as a long-term control,
- Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study,
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.REP1Also: Adeno-associated viral vectorSingle subretinal injection of rAAV2.REP1 vector suspension containing 10e12 genome particles per ml. Dose 1 = dose containing approximately 10e10 rAAV2.REP1 genome particles. Dose 2 = dose containing approximately 10e11 rAAV2.REP1 genome particles. | Drug | Dose 1, Dose 2 |
Primary outcome
Visual acuity
Time frame: 6 months
Best corrected visual acuity, following cataract surgery if indicated
1 secondary outcome
Microperimetry, OCT and fundus autofluorescence
Time frame: 24 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 17 Nov 2017.
- Derived from this study: PubMed 27820636Simunovic MP, Jolly JK, Xue K, Edwards TL, Groppe M, Downes SM, MacLaren RE. The Spectrum of CHM Gene Mutations in Choroideremia and Their Relationship to Clinical Phenotype. Invest Ophthalmol Vis Sci. 2016 Nov 1;57(14):6033-6039. doi: 10.1167/iovs.16-20230.
- Derived from this study: PubMed 27403996Xue K, Oldani M, Jolly JK, Edwards TL, Groppe M, Downes SM, MacLaren RE. Correlation of Optical Coherence Tomography and Autofluorescence in the Outer Retina and Choroid of Patients With Choroideremia. Invest Ophthalmol Vis Sci. 2016 Jul 1;57(8):3674-84. doi: 10.1167/iovs.15-18364.
- Derived from this study: PubMed 25744334Seitz IP, Zhour A, Kohl S, Llavona P, Peter T, Wilhelm B, Zrenner E, Ueffing M, Bartz-Schmidt KU, Fischer MD. Multimodal assessment of choroideremia patients defines pre-treatment characteristics. Graefes Arch Clin Exp Ophthalmol. 2015 Dec;253(12):2143-50. doi: 10.1007/s00417-015-2976-4. Epub 2015 Mar 7.
- Derived from this study: PubMed 24439297MacLaren RE, Groppe M, Barnard AR, Cottriall CL, Tolmachova T, Seymour L, Clark KR, During MJ, Cremers FP, Black GC, Lotery AJ, Downes SM, Webster AR, Seabra MC. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. 2014 Mar 29;383(9923):1129-37. doi: 10.1016/S0140-6736(13)62117-0. Epub 2014 Jan 16.
Related trials for Choroideremia
RecruitingObservational study
Inherited Retinal Degenerative Disease Registry
Eye Diseases Hereditary, Retinal Disease
RecruitingObservational study
High Resolution Retinal Imaging
Stargardts, Retinitis Pigmentosa
Active, not recruitingPhase 1
Study to Evaluate Safety of RTx-015 Injection in Retinitis Pigmentosa or Choroideremia Patients (ENVISION)
Retinitis Pigmentosa, Choroideremia
Recruiting
HYPER MIND - Hyperoxia Effects on Cerebral Hemodynamics
Hyperoxemia, Cerebrovascular Circulation
Active, not recruitingPhase 1
Dose Escalation Study of Intravitreal 4D-110 in Patients With Choroideremia
Choroideremia
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.
Robert E MacLaren, MB ChB DPhil study chair
University of Oxford, Oxford Radcliffe Hospitals NHS Trust and Moorfields Eye Hospital
Miguel C Seabra, MD PhD principal investigator
Imperial College London
Andrew R Webster, MD principal investigator
UCL Institute of Ophthalmology and Moorfields Eye Hospital
4 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.REP1 in people with Choroideremia, run by University of Oxford at 4 sites 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 6 inclusion and 6 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 17 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Visual acuity (time frame: 6 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 NCT01461213, which also lists 4 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 17 Nov 2017; AzTrials last refreshed its copy on 1 Nov 2026.