Table 1. Choroideremia gene therapy trials.
AAV2 – adeno-associated viral vector serotype 2, CAG – ubiquitous cytomegalovirus-enhanced chicken beta-actin promoter, CHM – choroideremia transgene, WPRE – woodchuck hepatitis virus posttranscriptional regulatory element, polyA – a modified bovine polyadenylation signal, REP1 – Rab escort protein 1.
| Clinical trial registration (clinicaltrials.gov) | Location/Start Date | Phase/Design | Reference |
|---|---|---|---|
| NCT01461213 | University of Oxford, UK October 2011 |
Phase I/II Low and high dose, open label 14 male participants, Subretinal injection AAV2-REP1 (AAV2-CAG-CHM-WPRE-polyA) |
Lancet, 2014 doi: 10.1016/S0140-6736(13)62117-0 NEJM, 2015 doi: 10.1056/NEJMc1509501 Nat Med, 2018 doi: 10.1038/s41591-018-0185-5 |
| NCT02341807 | Philadelphia, USA Spark Therapeutics January 2015 |
Phase I/II Low and high dose, open label 15 male participants, Subretinal injection AAV2-REP1 (AAV2-CAG-CHM-polyA) |
No reports to date |
| NCT02077361 | University of Alberta, Canada April 2015 |
Phase I/II Single dose, open label 6 male participants, Subretinal injection AAV2-REP1 (AAV2-CAG-CHM-WPRE-polyA) |
Am J Ophthalmol, 2018 doi: 10.1016/j.ajo.2018.06.011 |
| NCT02553135 | University of Miami, USA September 2015 |
Phase II Single dose, open label 6 male participants, Subretinal injection AAV2-REP1 (AAV2-CAG-CHM-WPRE-polyA) |
Am J Ophthalmol, 2019 doi: 10.1016/j.ajo.2018.09.012 |
| NCT02671539 | University of Tubingen, Germany THOR TRIAL January 2016 |
Phase II Single dose, open label 6 male participants, ubretinal injection AAV2-REP1 (AAV2-CAG-CHM-WPRE-polyA) |
Retina, 2018 doi: 10.1097/IAE.0000000000002360 |
| NCT02407678 | University of Oxford and Moorfields Eye Hospital, UK REGENERATE TRIAL August 2016 |
Phase II Randomised, single dose, open label 30 male participants, Subretinal injection AAV2-REP1 (AAV2-CAG-CHM-WPRE-polyA) |
No reports to date |
| NCT03507686 | Nightstar Therapeutics, International, Multi-centre GEMINI TRIAL November 2017 |
Phase II Single dose, open label, two-period 15 male participants, Bilateral subretinal injection AAV2-REP1 (AAV2-CAG-CHM-WPRE-polyA) |
No reports to date |
| NCT03496012 | Nightstar Therapeutics, International, Multi-centre STAR TRIAL December 2017 |
Phase III Control, low, high doseA Randomised, Open Label, Outcomes-Assessor Masked, Prospective, Parallel Controlled Group Study 140 male participants, Subretinal injection AAV2-REP1 (AAV2-CAG-CHM-WPRE-polyA) |
No reports to date |
| NCT03584165 | Nightstar Therapeutics, International, Multi-centre SOLSTICE TRIAL June 2018 |
Observational, Long-term follow up evaluating the safety and efficacy of AAV2-REP1 used in antecedent choroideremia studies, 100 participants |
No reports to date |
| NCT03359551 | Nightstar Therapeutics, International, Multi-centre NIGHT STUDY June 2015 |
Observational, Prospective, Natural History of the Progression of Choroideremia, 300 participants |
Am J Ophthalmol, 2017 doi: 10.1016/j.ajo.2017.05.002 Br J Ophthalmol, 2019 doi: 10.1136/bjophthalmol-2018-312620. |