Clinical Trials Resource Center

Leber's Hereditary Optic Neuropathy (LHON)

December 18, 2017

GenSight Biologics reported 2.5 years of follow-up data from its phase I/II clinical trial of GS010 in patients with Leber Hereditary Optic Neuropathy (LHON). These results confirm longterm sustained gains in visual acuity 2.5 years after a single intravitreal injection of GS010, especially in subjects with less than two years of onset of vision loss. In the study, five cohorts of three subjects were administered an increasing dose of GS010 via a single intravitreal injection in the eye more severely affected by the disease. Recruitment of 15 subjects was completed in April 2015 and long-term follow-up is ongoing. Subjects had an average onset of vision loss of six years at the time of treatment. At baseline, both treated (TE) and untreated (UTE) eyes had an off-chart median visual acuity. At year 2.5 post-injection, in subjects less than two years from onset of vision loss and with relatively better vision at the time of treatment (<2.79 LogMAR), TE had a mean gain of +28 ETDRS letters (0.55 LogMAR) compared to baseline, while UTE had a mean gain of +13 ETDRS letters ( 0.25 LogMAR) compared to baseline. The difference of +15 ETDRS letters in favor of TE is clinically significant, and the magnitude of the improvement, which is similar to the trend observed at weeks 48, 78, and 96, suggests sustained benefit from GS010. The subject group (n=5) with an onset of vision loss of less than two years and relatively better vision at the time of injection (<2.79 LogMAR) demonstrated a sustained pharmacological trend in favor of the treated eye, of increasing magnitude from week 36 onward, with 60% of subjects showing a clinically significant gain of ≥ 15 letters in TE at year 2.5. At year 2.5 post-injection, GS010 continued to demonstrate a favorable tolerability profile, with no reports of worsening vision or ocular sequelae, serious treatment-emergent adverse events (TEAEs), nor systemic adverse events (AEs) related to GS010 or its administration. GenSight Biologics is currently conducting two phase III clinical studies (RESCUE and REVERSE) in Europe and the U.S. to assess the efficacy of GS010 in subjects affected with LHON due to the ND4 mutation, and with vision loss up to one year at the time of treatment.

June 13, 2016

GenSight Biologics issued results of a phase I/II study designed to demonstrate the safety and tolerability of GS010 in 15 patients with Leber’s Hereditary Optic Neuropathy (LHON). Each cohort of three patients was administered an escalating dose of GS010 through a single intravitreal injection in the eye most severely affected by the disease. At 48 weeks post-injection, in patients with an onset of disease of less than two years, a gain of +30 letters (-0.59 LogMAR) was observed in the treated eye and +13 letters (-0.25 LogMAR) in the untreated eye, a difference of 17 letters in favor of the treated eye. No significant difference was observed in patients with an onset of disease of more than two years. The combined effect of the administered dose and the time from onset is noticeable at 36 weeks and stable after 48 weeks. Gensight Biologics is currently conducting two phase III clinical studies (Rescue and Reverse) in Europe and the U.S. to assess the efficacy of GS010 in patients affected with LHON due to the ND4 mutation, with an onset of vision loss of less than one year. The top-line results at 48 weeks follow-up are expected in late 2017.

June 21, 2010

Santhera released positive results from a phase III trial of Catena for the treatment of Leber's Hereditary Optic Neuropathy (LHON). This double-blind, randomized, placebo-controlled study, dubbed RHODOS (Rescue Of Hereditary Optic Disease Outpatient Study), enrolled 85 acute patients as well as those experiencing vision loss for up to five years. Treatment took place in Germany, the United Kingdom and Canada. The subjects received Catena 900 mg/day or placebo. The primary endpoint was the best recovery in visual acuity in either eye measured by change in logMAR between baseline and week 24. In the intent-to-treat population (n≡82) the subjects receiving Catena improved on average by six letters while subjects receiving placebo improved by three letters (p≡0.291). A secondary endpoint was best visual acuity at week 24 compared to best visual acuity at baseline. The visual acuity in the Catena group was five letters better at week 24 than the placebo group (p%equiv;0.078). In a prespecified secondary endpoint analyzing the change of all subjects' eyes separately to increase the power of the study, the visual acuity of eyes of patients receiving Catena significantly improved compared to those receiving placebo (p=0.026). A responder analyses of subjects who were unable to read the eye-chart at baseline showed that seven out of 25 (28%) receiving Catena recovered sufficient visual acuity to read at least five letters on the eye chart compared to zero out of 13 (0%) individuals in the placebo group (p≡.072).

May 5, 2008

Targeted Genetics reported positive results from a phase I/II trial of their RPE65 gene therapy for the treatment of retinal dystrophy due to Leber's congenital amaurosis (LCA). This single-center, open label study enrolled nine young adults, between the ages of 17 and 23 years, with early-onset severe retinal dystrophy due to LCA. The subjects were administered a single subretinal injection of the AAV vector expressing RPE65. In each subject, the eye with the worse acuity was selected as the study eye and the other was used as a control. After two weeks, data from the first three treated subjects showed that they had improved vision in the injected eye and could read several lines on an eye chart. They also had less nystagmus after six months and one subject showed a significant consistent improvement in visual function and subjective tests of visual mobility No adverse events or inflammation were reported. Based on the results the company planned to enroll additional subjects into the trial.

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