Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium

Debra A Thompson¹, Alessandro Iannaccone², Robin R Ali^{1

3}, Vadim Y Arshavsky², Isabelle Audo^{4

5}, James W B Bainbridge³, Cagri G Besirli¹, David G Birch⁶, Kari E Branham¹, Artur V Cideciyan⁷, Steven P Daiger⁸, Deniz Dalkara⁴, Jacque L Duncan⁹, Abigail T Fahim¹, John G Flannery¹⁰, Roberto Gattegna¹¹, John R Heckenlively¹, Elise Heon¹², K Thiran Jayasundera¹, Naheed W Khan¹, Henry Klassen¹³, Bart P Leroy^{14

15}, Robert S Molday¹⁶, David C Musch¹, Mark E Pennesi¹⁷, Simon M Petersen-Jones¹⁸, Eric A Pierce¹⁹, Rajesh C Rao¹, Thomas A Reh²⁰, Jose A Sahel^{4

5

21

22}, Dror Sharon²³, Paul A Sieving^{24

25}, Enrica Strettoi²⁶, Paul Yang¹⁷, David N Zacks¹; Monaciano Consortium

Affiliations

¹ Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA.
² Department of Ophthalmology, Duke Eye Center, Duke University Medical Center, Durham, NC, USA.
³ Institute of Ophthalmology, University College London, London, UK.
⁴ Sorbonne Université, Institut de la Vision, INSERM, CNRS, Paris, France.
⁵ CHNO des Quinze-Vingts, INSERM-DGOS CIC 1423, Paris, France.
⁶ Retina Foundation of the Southwest, Dallas, TX, USA.
⁷ Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁸ Human Genetics Center, School of Public Health, University of Texas Health Science Center Houston, Houston, TX, USA.
⁹ Department of Ophthalmology, University of California-San Francisco, San Francisco, CA, USA.
¹⁰ Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA, USA.
¹¹ Retina Service, Israelitic Hospital, Roma, Italy.
¹² Department of Ophthalmology and Vision Sciences, Hospital for Sick Children, Toronto, Ontario, Canada.
¹³ Gavin Herbert Eye Institute, Stem Cell Research Center, University of California-Irvine, Irvine, CA, USA.
¹⁴ Department of Ophthalmology and Center Medical Genetics, Ghent University Hospital and University, Ghent, Belgium.
¹⁵ Division of Ophthalmology and Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹⁶ Department of Biochemistry/Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁷ Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science Center, Portland, OR, USA.
¹⁸ Small Animal Clinical Sciences, Michigan State University, College of Veterinary Medicine, East Lansing, MI, USA.
¹⁹ Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
²⁰ Department of Biological Structure, University of Washington, Seattle, WA, USA.
²¹ Fondation Ophtalmologique Rothschild, Paris, France.
²² Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²³ Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
²⁴ Department of Ophthalmology and Center for Ocular Regenerative Therapy, University of California-Davis School of Medicine, Sacramento, CA, USA.
²⁵ National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
²⁶ Institute of Neuroscience, National Research Council (CNR), Pisa, Italy.

PMID: 32832209
PMCID: PMC7414644
DOI: 10.1167/tvst.9.7.2

Review

Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium

Debra A Thompson et al. Transl Vis Sci Technol. 2020.

. 2020 Jun 3;9(7):2.

doi: 10.1167/tvst.9.7.2. eCollection 2020 Jun.

Authors

Affiliations

¹ Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA.
² Department of Ophthalmology, Duke Eye Center, Duke University Medical Center, Durham, NC, USA.
³ Institute of Ophthalmology, University College London, London, UK.
⁴ Sorbonne Université, Institut de la Vision, INSERM, CNRS, Paris, France.
⁵ CHNO des Quinze-Vingts, INSERM-DGOS CIC 1423, Paris, France.
⁶ Retina Foundation of the Southwest, Dallas, TX, USA.
⁷ Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁸ Human Genetics Center, School of Public Health, University of Texas Health Science Center Houston, Houston, TX, USA.
⁹ Department of Ophthalmology, University of California-San Francisco, San Francisco, CA, USA.
¹⁰ Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA, USA.
¹¹ Retina Service, Israelitic Hospital, Roma, Italy.
¹² Department of Ophthalmology and Vision Sciences, Hospital for Sick Children, Toronto, Ontario, Canada.
¹³ Gavin Herbert Eye Institute, Stem Cell Research Center, University of California-Irvine, Irvine, CA, USA.
¹⁴ Department of Ophthalmology and Center Medical Genetics, Ghent University Hospital and University, Ghent, Belgium.
¹⁵ Division of Ophthalmology and Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹⁶ Department of Biochemistry/Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁷ Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science Center, Portland, OR, USA.
¹⁸ Small Animal Clinical Sciences, Michigan State University, College of Veterinary Medicine, East Lansing, MI, USA.
¹⁹ Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
²⁰ Department of Biological Structure, University of Washington, Seattle, WA, USA.
²¹ Fondation Ophtalmologique Rothschild, Paris, France.
²² Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²³ Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
²⁴ Department of Ophthalmology and Center for Ocular Regenerative Therapy, University of California-Davis School of Medicine, Sacramento, CA, USA.
²⁵ National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
²⁶ Institute of Neuroscience, National Research Council (CNR), Pisa, Italy.

PMID: 32832209
PMCID: PMC7414644
DOI: 10.1167/tvst.9.7.2

Abstract

Major advances in the study of inherited retinal diseases (IRDs) have placed efforts to develop treatments for these blinding conditions at the forefront of the emerging field of precision medicine. As a result, the growth of clinical trials for IRDs has increased rapidly over the past decade and is expected to further accelerate as more therapeutic possibilities emerge and qualified participants are identified. Although guided by established principles, these specialized trials, requiring analysis of novel outcome measures and endpoints in small patient populations, present multiple challenges relative to study design and ethical considerations. This position paper reviews recent accomplishments and existing challenges in clinical trials for IRDs and presents a set of recommendations aimed at rapidly advancing future progress. The goal is to stimulate discussions among researchers, funding agencies, industry, and policy makers that will further the design, conduct, and analysis of clinical trials needed to accelerate the approval of effective treatments for IRDs, while promoting advocacy and ensuring patient safety.

Keywords: clinical trials; counseling patients; inherited retinal diseases; natural history studies; outcome measures.

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Conflict of interest statement

Disclosure: D.A. Thompson, MeiraGTx (F), filed patent on gene therapy (P); A. Iannaccone, Editas Medicine (C), Astellas (C), Roivant Pharma (C), IQVIA (C), Gyroscope/Orbit Biomedical (C), Rhythm Pharmaceuticals (C), Applied Genetic Technologies Corp (F), Allergan (F), Acucela (F), ProQR Therapeutics (F), Foundation Fighting Blindness Clinical Research Institute (F), Alia Therapeutics (S); R.R. Ali, MeiraGTx (S), filed patents on gene and cell therapies (P); V.Y. Arshavsky, None; I. Audo, None; J.W.B. Bainbridge, MeiraGTx (S), filed patents on gene and cell therapies (P); C.G. Besirli, MeiraGTx (F), Spark Therapeutics (F); D.G. Birch, Nightstar Therapeutics/Biogen (C), Applied Genetic Technologies Corp (S), Nacuity Pharmaceuticals (C), Editas Medicine (C), Acucela (S), Foundation Fighting Blindness (C), ProQR Therapeutics (C); K.E. Branham, ProQR Therapeutics (C); A.V. Cideciyan, Patents on gene therapies for RPGR, RHO, and NPHP5-associated IRDs (P); ProQR Therapeutics (F), IVERIC bio (F); S.P. Daiger, Applied Genetic Technologies Corp (S); D. Dalkara, Patent on AAV virions with variant capsid and methods of use (P); J.L. Duncan, 4D Therapeutics (C), Applied Genetic Technologies Corp (C), Editas Medicine (C), Gyroscope (C), Horama (C), Nightstar Therapeutics/Biogen (C), ProQR Therapeutics (C), SparingVision (S), Spark Therapeutics (C), Vedere Bio (C), Acucela (F), Allergan (F), Neurotech (F), Second Sight Medical Products (F); A.T. Fahim, None; J.G. Flannery, None; R. Gattegna, None; J.R. Heckenlively, None; E. Heon, None; K.T. Jayasundera, Editas Medicine (C); N.W. Khan, None; H. Klassen, jCyte (S, I); B.P. Leroy, Bayer (C), Nightstar Therapeutics/Biogen (C), IVERIC bio (C), Novartis Pharma (C), RegenX Bio (C), Vedere Bio (C); Novartis (R), Spark Therapeutics (R); GenSight Biologics (F), ProQR Therapeutics (F); R.S. Molday, Applied Genetic Technologies Corp (S); D.C. Musch, Belite Bio (S), Mactel Group NTMT-03 trial (S), NEI intramural branch clinical trials (S); M.E. Pennesi, Adverum (C), Allergan (C), Astellas (C), Pharmaceuticals (C), Biogen (C), IVERIC bio (C), Novartis (C), Regenix Bio (C), Spark Therapeutics (C), Wave Biosciences (C), Eyevensys (S), Horama (S), Nayan (S), Nacuity Pharmaceuticals (S, I), Ocugen (S, I), Verede (S), ProQR Therapeutics (S), Gensight (S), Applied Genetic Technologies Corp (F), Sanofi (F), Foundation Fighting Blindness (F), ProQR Therapeutics (F), Allergan (F); S.M. Petersen-Jones, None; E.A. Pierce, Astellas (C), Merck (C), Sanofi-Genzyme (C), Wave Therapeutics (C); GenSight Biologics (S), Odylia Therapeutics (S), Opsis Therapeutics (S), Sana Biotechnology (S); CRISPR Therapeutics (F), Spark Therapeutics (F); Editas Medicine (F), MeiraGTx (F), ProQR Therapeutics (F), filed patents on gene and genetic therapies (P); R.C. Rao, None; T.A. Reh, Nayan Pharmaceuticals (C, I); J.A. Sahel, Pixium Vision (S, I), GenSight Biologics (S, I), SparingVision (S, I); Prophesee (I), Chronolife (I); D. Sharon, None; P.A. Sieving, None; E. Strettoi, None; P. Yang, Astellas (C), Applied Genetic Technologies Corp (C); D.N. Zacks, ONL Therapeutics (C, I, P)

References

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Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium

Affiliations

Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous