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PLoS One. 2015 Dec 10;10(12):e0143846. doi: 10.1371/journal.pone.0143846. eCollection 2015.

Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT).

Author information

1
Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, United States of America.
2
Moorfields Eye Hospital and Institute of Ophthalmology, University College London, London, United Kingdom.
3
Dept. of Ophthalmology, University of California San Francisco, San Francisco, CA, United States of America.
4
McGill University Health Centre, Montreal, Quebec, Canada.
5
Retina Foundation of the Southwest, Dallas, TX, United States of America.
6
Baylor Visual Function Center, Baylor University Medical Center, Dallas, TX, United States of America.
7
Chicago Lighthouse, Pangere Center for Inherited Retinal Diseases, Chicago, IL, United States of America.
8
Rotterdam Eye Hospital and Ophthalmic Institute, Rotterdam, The Netherlands.
9
Nova Southeastern University, College of Optometry, Fort Lauderdale, FL, United States of America.
10
College of Optometry, University of Houston, Houston, TX, United States of America.
11
Gloucester Royal NHS Foundation Trust, Gloucester Royal Hospitals, Gloucester, United Kingdom.
12
Vitreoretinal Associates of Washington, Seattle, WA, United States of America.
13
QLT Inc., Vancouver, Canada.
14
Stanford Univ School of Medicine, Palo Alto, CA, United States of America.
15
VA Palo Alto Health Care System, Palo Alto, CA, United States of America.
16
Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, MD, United States of America.
17
Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany.
18
Ophthalmology, UT Southwestern, Dallas, TX, United States of America.

Abstract

Restoring vision in inherited retinal degenerations remains an unmet medical need. In mice exhibiting a genetically engineered block of the visual cycle, vision was recently successfully restored by oral administration of 9-cis-retinyl acetate (QLT091001). Safety and visual outcomes of a once-daily oral dose of 40 mg/m2/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18 patients with RPE65- or LRAT-related retinitis pigmentosa. Eight of 18 patients (44%) showed a ≥20% increase and 4 of 18 (22%) showed a ≥40% increase in functional retinal area determined from Goldmann visual fields; 12 (67%) and 5 (28%) of 18 patients showed a ≥5 and ≥10 ETDRS letter score increase of visual acuity, respectively, in one or both eyes at two or more visits within 2 months of treatment. In two patients who underwent fMRI, a significant positive response was measured to stimuli of medium contrast, moving, pattern targets in both left and right hemispheres of the occipital cortex. There were no serious adverse events. Treatment-related adverse events were transient and the most common included headache, photophobia, nausea, vomiting, and minor biochemical abnormalities. Measuring the outer segment length of the photoreceptor layer with high-definition optical coherence tomography was highly predictive of treatment responses with responders having a significantly larger baseline outer segment thickness (11.7 ± 4.8 μm, mean ± 95% CI) than non-responders (3.5 ± 1.2 μm). This structure-function relationship suggests that treatment with QLT091001 is more likely to be efficacious if there is sufficient photoreceptor integrity.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01014052.

PMID:
26656277
PMCID:
PMC4687523
DOI:
10.1371/journal.pone.0143846
[Indexed for MEDLINE]
Free PMC Article

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