Outcome Measures Used in Ocular Gene Therapy Trials: A Scoping Review of Current Practice

被引：27

作者：

Jolly, Jasleen K. ^{[1
,2
,3
]}

Bridge, Holly ^{[2
]}

MacLaren, Robert E. ^{[1
,3
]}

机构：

[1] Univ Oxford, Nuffield Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford, England

[2] Univ Oxford, Nuffield Dept Clin Neurosci, Wellcome Integrat Neuroimaging Ctr, Oxford, England

[3] Oxford Univ Hosp NHS Fdn Trust, Oxford Eye Hosp, Oxford, England

来源：

FRONTIERS IN PHARMACOLOGY | 2019年 / 10卷

关键词：

clinical trial; gene therapy; genetic eye disease; outcome measure; retinal imaging; vision; visual function; LEBER CONGENITAL AMAUROSIS; 3-YEAR FOLLOW-UP; MACULAR DEGENERATION; ADENOASSOCIATED VIRUS; RPE65; MUTATIONS; SUBRETINAL INJECTION; INITIAL FINDINGS; VISUAL FUNCTION; OPEN-LABEL; SAFETY;

D O I：

10.3389/fphar.2019.01076

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Multiple gene therapy trials are occurring for a variety of ophthalmic diseases around the world. The safety of gene therapy in the eye has been established, and the next step is to reliably assess efficacy. This is primarily done through the use of imaging techniques and visual function measures. Standardized visual function assessments, however, were originally developed for a clinical setting and may not be suitable for detecting and quantifying therapeutic changes. This scoping review takes a comprehensive look at current practice in terms of the outcome measures defined at trial registration. These were compared to the outcome measures reported in the literature. All published trials reported the pre-registered primary outcome measure. A range of additional secondary outcomes were reported that were not originally planned. Gaps in gene therapy assessment exist and further discussion are required to find a way forward, particularly as more conditions progress to phase 2 and 3 trials. Several factors impacting on trial design and outcome measure choice are discussed.

引用

页数：7

共 46 条

[1] The human visual cortex responds to gene therapy-mediated recovery of retinal function [J].

Ashtari, Manzar ;

Cyckowski, Laura L. ;

Monroe, Justin F. ;

Marshall, Kathleen A. ;

Chung, Daniel C. ;

Auricchio, Alberto ;

Simonelli, Francesca ;

Leroy, Bart P. ;

Maguire, Albert M. ;

Shindler, Kenneth S. ;

Bennett, Jean .

JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (06) :2160-2168

[2] Long-Term Effect of Gene Therapy on Leber's Congenital Amaurosis [J].

Bainbridge, J. W. B. ;

Mehat, M. S. ;

Sundaram, V. ;

Robbie, S. J. ;

Barker, S. E. ;

Ripamonti, C. ;

Georgiadis, A. ;

Mowat, F. M. ;

Beattie, S. G. ;

Gardner, P. J. ;

Feathers, K. L. ;

Luong, V. A. ;

Yzer, S. ;

Balaggan, K. ;

Viswanathan, A. ;

de Ravel, T. J. L. ;

Casteels, I. ;

Holder, G. E. ;

Tyler, N. ;

Fitzke, F. W. ;

Weleber, R. G. ;

Nardini, M. ;

Moore, A. T. ;

Thompson, D. A. ;

Petersen-Jones, S. M. ;

Michaelides, M. ;

van den Born, L. I. ;

Stockman, A. ;

Smith, A. J. ;

Rubin, G. ;

Ali, R. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (20) :1887-1897

[3] Effect of gene therapy on visual function in Leber's congenital amaurosis [J].

Bainbridge, James W. B. ;

Smith, Alexander J. ;

Barker, Susie S. ;

Robbie, Scott ;

Henderson, Robert ;

Balaggan, Kamaljit ;

Viswanathan, Ananth ;

Holder, Graham E. ;

Stockman, Andrew ;

Tyler, Nick ;

Petersen-Jones, Simon ;

Bhattacharya, Shomi S. ;

Thrasher, Adrian J. ;

Fitzke, Fred W. ;

Carter, Barrie J. ;

Rubin, Gary S. ;

Moore, Anthony T. ;

Ali, Robin R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (21) :2231-2239

[4] Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial [J].

Bennett, Jean ;

Wellman, Jennifer ;

Marshall, Kathleen A. ;

McCague, Sarah ;

Ashtari, Manzar ;

DiStefano-Pappas, Julie ;

Elci, Okan U. ;

Chung, Daniel C. ;

Sun, Junwei ;

Wright, J. Fraser ;

Cross, Dominique R. ;

Aravand, Puya ;

Cyckowski, Laura L. ;

Bennicelli, Jeannette L. ;

Mingozzi, Federico ;

Auricchio, Alberto ;

Pierce, Eric A. ;

Ruggiero, Jason ;

Leroy, Bart P. ;

Simonelli, Francesca ;

High, Katherine A. ;

Maguire, Albert M. .

LANCET, 2016, 388 (10045) :661-672

[5]

Boote J, 2011, TRIALS S1, V12, pA82, DOI DOI 10.1186/1745-6215-12-S1-A82]

[6] Lentiviral Vector Gene Transfer of Endostatin/Angiostatin for Macular Degeneration (GEM) Study [J].

Campochiaro, Peter A. ;

Lauer, Andreas K. ;

Sohn, Elliott H. ;

Mir, Tahreem A. ;

Naylor, Stuart ;

Anderton, Matthew C. ;

Kelleher, Michelle ;

Harrop, Richard ;

Ellis, Scott ;

Mitrophanous, Kyriacos A. .

HUMAN GENE THERAPY, 2017, 28 (01) :99-111

[7] Pseudo-Fovea Formation After Gene Therapy for RPE65-LCA [J].

Cideciyan, Artur V. ;

Aguirre, Geoffrey K. ;

Jacobson, Samuel G. ;

Butt, Omar H. ;

Schwartz, Sharon B. ;

Swider, Malgorzata ;

Roman, Alejandro J. ;

Sadigh, Sam ;

Hauswirth, William W. .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2015, 56 (01) :526-537

[8] Human RPE65 Gene Therapy for Leber Congenital Amaurosis: Persistence of Early Visual Improvements and Safety at 1 Year [J].

Cideciyan, Artur V. ;

Hauswirth, William W. ;

Aleman, Tomas S. ;

Kaushal, Shalesh ;

Schwartz, Sharon B. ;

Boye, Sanford L. ;

Windsor, Elizabeth A. M. ;

Conlon, Thomas J. ;

Sumaroka, Alexander ;

Pang, Ji-jing ;

Roman, Alejandro J. ;

Byrne, Barry J. ;

Jacobson, Samuel G. .

HUMAN GENE THERAPY, 2009, 20 (09) :999-1004

[9] Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics [J].

Cideciyan, Artur V. ;

Aleman, Tomas S. ;

Boye, Sanford L. ;

Schwartz, Sharon B. ;

Kaushal, Shalesh ;

Roman, Alejandro J. ;

Pang, Ji-Jing ;

Sumaroka, Alexander ;

Windsor, Elizabeth A. M. ;

Wilson, James M. ;

Flotte, Terence R. ;

Fishman, Gerald A. ;

Heon, Elise ;

Stone, Edwin M. ;

Byrne, Barry J. ;

Jacobson, Samuel G. ;

Hauswirth, William W. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (39) :15112-15117

[10] Gene Therapy in Neovascular Age-related Macular Degeneration: Three-Year Follow-up of a Phase 1 Randomized Dose Escalation Trial [J].

Constable, Ian J. ;

Lai, Chooi-May ;

Magno, Aaron L. ;

French, Martyn A. ;

Barone, Samuel B. ;

Schwartz, Steven D. ;

Blumenkranz, Mark S. ;

Degli-Esposti, Mariapia A. ;

Rakoczy, Elizabeth P. .

AMERICAN JOURNAL OF OPHTHALMOLOGY, 2017, 177 :150-158

← 1 2 3 4 5 →