June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Efficacy and safety of sepofarsen, an intravitreal RNA antisense oligonucleotide, for the treatment of CEP290-associated Leber congenital amaurosis (LCA10): a randomized, double-masked, sham-controlled, Phase 3 study (ILLUMINATE)
Author Affiliations & Notes
  • Bart Peter Leroy
    Department of Head & Skin, Universiteit Gent, Gent, East-Flanders, Belgium
    Department of Ophthalmology, Ghent University Hospital, Ghent, East-Flanders, Belgium
  • Katarina Stingl
    Center for Ophthalmology, University Eye Hospital, University of Tübingen, Tübingen, Germany
    Center for Rare Eye Diseases, Eberhard Karls Universitat Tubingen, Tubingen, Baden-Württemberg, Germany
  • Isabelle S Audo
    Centre de référence maladies rares REFERET and INSERM-DHOS CIC 1423, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, Île-de-France, France
    INSERM, CNRS, Institut de la Vision, Sorbonne Universite, Paris, Île-de-France, France
  • Camiel J F Boon
    Department of Ophthalmology, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
    Department of Ophthalmology, AMC, Universiteit van Amsterdam, Amsterdam, Noord-Holland, Netherlands
  • Fernanda Belga O Porto
    INRET Clínica e Centro de Pesquisa, Belo Horizonte, Minas Gerais, Brazil
    Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, IEP/SCBH, Belo Horizonte, Minas Gerais, Brazil
  • Michel Michaelides
    Institute of Ophthalmology, University College London, London, London, United Kingdom
    Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Helene Dollfus
    Centre des Affections Rares en Génétique Ophtalmologique (CARGO), Universite de Strasbourg, Strasbourg, Grand Est, France
  • L. Ingeborgh van den Born
    The Rotterdam Eye Hospital, Rotterdam, Zuid-Holland, Netherlands
  • Lyubomyr M Lytvynchuk
    Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Hesse, Germany
    Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Vienna, Austria
  • Francesca Simonelli
    Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, Universita degli Studi della Campania Luigi Vanvitelli, Naples, Campania, Italy
  • Juliana M F Sallum
    Department of Ophthalmology, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
    Instituto de Genética Ocular, São Paulo, São Paulo, Brazil
  • Robert K Koenekoop
    Department of Paediatric Surgery, Human Genetics and Adult Ophthalmology, MUHC, Montreal, Quebec, Canada
  • Elise Heon
    Genetics and Genome Biology (GGB) Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
    Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Stephen R Russell
    Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa, United States
  • Michael Schwartz
    ProQR Therapeutics NV, Leiden, Zuid-Holland, Netherlands
  • Aniz Girach
    ProQR Therapeutics NV, Leiden, Zuid-Holland, Netherlands
  • Footnotes
    Commercial Relationships   Bart Leroy ProQR, Code C (Consultant/Contractor), ProQR, Code F (Financial Support); Katarina Stingl ProQR, Code C (Consultant/Contractor), ProQR, Code F (Financial Support); Isabelle Audo ProQR, Code C (Consultant/Contractor), ProQR, Code F (Financial Support); Camiel Boon None; Fernanda Porto None; Michel Michaelides None; Helene Dollfus None; L. van den Born None; Lyubomyr Lytvynchuk ProQr Therapeutics, Code F (Financial Support); Francesca Simonelli ProQR, Code C (Consultant/Contractor), ProQR, Code F (Financial Support); Juliana Sallum None; Robert Koenekoop ProQR, Code C (Consultant/Contractor); Elise Heon None; Stephen Russell ProQR, Code F (Financial Support); Michael Schwartz ProQR, Code E (Employment); Aniz Girach ProQR, Code E (Employment)
  • Footnotes
    Support  Research Foundation Flanders, Senior Clinical Investigator Award (1803821N) & Concerted Research Action of the Special Research Fund Ghent University (BOF20/GOA/023)
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4536 – F0323. doi:
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      Bart Peter Leroy, Katarina Stingl, Isabelle S Audo, Camiel J F Boon, Fernanda Belga O Porto, Michel Michaelides, Helene Dollfus, L. Ingeborgh van den Born, Lyubomyr M Lytvynchuk, Francesca Simonelli, Juliana M F Sallum, Robert K Koenekoop, Elise Heon, Stephen R Russell, Michael Schwartz, Aniz Girach; Efficacy and safety of sepofarsen, an intravitreal RNA antisense oligonucleotide, for the treatment of CEP290-associated Leber congenital amaurosis (LCA10): a randomized, double-masked, sham-controlled, Phase 3 study (ILLUMINATE). Invest. Ophthalmol. Vis. Sci. 2022;63(7):4536 – F0323.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : LCA10 is a severe, degenerative inherited retinal disease resulting in childhood blindness, which has no treatment. Sepofarsen, an RNA antisense oligonucleotide designed for LCA10 due to the frequent c.2991+1655A>G variant in the CEP290 gene, produced clinically meaningful improvements in visual acuity in a Phase 1b/2 trial. The aim of the phase 3 trial (ILLUMINATE) was to assess the efficacy and safety of sepofarsen compared to sham in c.2991+1655A>G-LCA10 participants.

Methods : ILLUMINATE (NCT03913143) was a double-masked, randomized, sham-controlled study performed across 14 sites in Europe, North America and Latin America. Eligible participants were aged ≥ 8 years, carried at least one c.2991+1655A>G in the CEP290 gene and had best-corrected visual acuity (BCVA) ranging from 0.4 (20/50 Snellen equivalent) to 3.0 logMAR (Hand Motion). Participants were randomly assigned (1:1:1) to receive intravitreal injection of sepofarsen 160/80 µg (maintenance dose of 80 µg every 6 months, starting 3 months after the loading dose of 160 µg), 80/40 µg (same regimen but doses of 40µg and 80µg respectively), or sham. The primary endpoint was mean change from baseline in BCVA, in the treatment eye (worse seeing eye), compared with sham at Month 12. Secondary endpoints included full-field stimulus testing threshold (FST; red, blue, white), a mobility course composite score, and safety. Trial recruitment was completed in January 2021.

Results : Between March 29, 2019 and January 6, 2021, 52 participants were screened, of whom 36 were randomized (group allocation masked at the time of abstract submission). At baseline, the mean age was 29.0 (SD 14.5) years, including 12 (SD 33.3%) participants aged 8 to 18 and 24 (66.7%) participants aged >18 years. Sixteen (44.4%) of the participants were homozygous for the target variant whereas 20 (55.6%) were compound heterozygous. Mean baseline BCVA in the treatment eye was 1.25 logMAR (SD 0.66) and mean baseline BCVA in the fellow eye was 1.01 logMAR (SD 0.27).

Conclusions : Sepofarsen, an innovative RNA antisense oligonucleotide, is the most advanced program in development for the treatment of LCA10. Learning from recruitment suggested the commonality of the c.2991+1655A>G variant in LCA10. Updated results will be included as available.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.


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