A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing RPE65 (rAAV2-CB-hRPE65) in Patients With Leber Congenital Amaurosis Type 2

The purpose of the study is to evaluate the safety and efficacy of an adeno-associated virus vector expressing RPE65 in patients with Leber congenital amaurosis caused by mutations in the RPE65 gene.
Funding Source - FDA OOPD

Start Date17 Jun 2009

Sponsor / Collaborator

Beacon Therapeutics (USA), Inc.

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100 Clinical Results associated with Leber congenital amaurosis gene therapy - Applied Genetic Technologies Corporation(Beacon Therapeutics)

100 Translational Medicine associated with Leber congenital amaurosis gene therapy - Applied Genetic Technologies Corporation(Beacon Therapeutics)

100 Patents (Medical) associated with Leber congenital amaurosis gene therapy - Applied Genetic Technologies Corporation(Beacon Therapeutics)

Literatures (Medical) associated with Leber congenital amaurosis gene therapy - Applied Genetic Technologies Corporation(Beacon Therapeutics)

18 Jun 2024·Translational Vision Science & Technology

Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector

Article

Author: Lauer, Andreas K ; Weleber, Richard G ; Ku, Cristy A ; Yang, Paul ; Igelman, Austin D ; Bailey, Steven T ; Duncan, Jacque L ; Huang, Samuel J ; Pennesi, Mark E

PurposeTo report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector.DesignSingle-center, retrospective chart review.MethodsIn this case series, four patients between the ages of six and 11 years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated.ResultsThree out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22 months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector.ConclusionsWe observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes.Translational RelevanceCaution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.

01 Dec 2018·Human Gene Therapy

Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy

Article

Author: Thean, Beverly ; Pennesi, Mark E. ; Flotte, Terence R. ; Chegarnov, Elvira ; Whitebirch, Chris ; Humphries, Margaret ; Stout, J. Timothy ; Chulay, Jeffrey D. ; Weleber, Richard G. ; Yang, Paul ; Beasley, Kathleen N.

Previously, results at 2 years after subretinal injection of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in eight adults and four children with retinal degeneration caused by RPE65 mutations were reported. Now, results at 5 years after treatment in 11 of these subjects are reported. Subjects received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of two dose levels, and were followed for 5 years after treatment. The primary safety outcomes were ocular and non-ocular adverse events. Efficacy outcomes included changes in best corrected visual acuity, static perimetry hill of vision measurements for the central 30° (V₃₀), and total (V_TOT) visual field and kinetic perimetry visual field area. The only adverse events reported during years 3, 4, and 5 were minor intercurrent illnesses. Pediatric subjects had improvement in visual acuity and static perimetry in the treated eye, sometimes with a smaller improvement in the untreated eye, during the first 2 years of the study that persisted during years 3-5, with no consistent changes in kinetic perimetry during the study. Most adult subjects had no consistent changes in visual acuity or static perimetry during the study. Three adult subjects with markedly abnormal baseline kinetic visual field area had improvement in the treated eye during the first 1-2 years after treatment, but the absolute magnitude of the improvement was small and was not sustained at subsequent visits. There were no clinically significant adverse events. Visual acuity and static perimetry testing results suggest that treating patients at a younger age is associated with better visual function outcomes during 5 years after treatment.

01 Jul 2016·OphthalmologyQ1 · MEDICINE

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood–Onset Retinal Dystrophy

Q1 · MEDICINE

Article

Author: Humphries, Margaret ; Hauswirth, William W ; Kaushal, Shalesh ; Jensen, Lauren ; Calcedo, Roberto ; Erker, Laura R ; McBride, Maureen T ; Flotte, Terence R ; Chulay, Jeffrey D ; Stout, J Timothy ; Pennesi, Mark E ; Wilson, David J ; Weleber, Richard G

PURPOSETo provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations.DESIGNNonrandomized, multicenter clinical trial.PARTICIPANTSEight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD).METHODSPatients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment.MAIN OUTCOME MEASURESThe primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire.RESULTSAll patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area.CONCLUSIONSTreatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns.

100 Deals associated with Leber congenital amaurosis gene therapy - Applied Genetic Technologies Corporation(Beacon Therapeutics)

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Indication	Highest Phase	Country/Location	Organization	Date
Leber Congenital Amaurosis	Phase 2	-	UMass Chan Medical School	-
Amaurosis Congenita of Leber, Type 2	Discovery	US	Beacon Therapeutics (USA), Inc.	17 Jun 2009

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00749957 (CTgov)	Phase 1/2	Amaurosis Congenita of Leber, Type 2	12	rAAV2-CB-hRPE65 (Lower Dose of rAAV2-CB-hRPE65)	nnojrxrkxn(xmetuqkhrx) = vvyfxaopfe ulycxldyfq (jktkkragyx, vafaqjdvbg - hqdpbyfvck) View more	-	08 Apr 2016
NCT00749957 (CTgov)	Phase 1/2	Amaurosis Congenita of Leber, Type 2	12	rAAV2-CB-hRPE65 (Higher Dose of rAAV2-CB-hRPE65)	nnojrxrkxn(xmetuqkhrx) = ljlfwjyght ulycxldyfq (jktkkragyx, hsqczmyhtk - verlpcbayk) View more	-	08 Apr 2016
ARVO2013	Not Applicable	Amaurosis Congenita of Leber, Type 2 RPE65 mutations	12	AAV Vector Expressing RPE65	(bnflqmamah) = aeutsfzrrj uztszagweq (almajltcsv ) View more	Positive	01 Jun 2013

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Leber congenital amaurosis gene therapy - Applied Genetic Technologies Corporation(Beacon Therapeutics)

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