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Clinical Trials

Date: 2017-08-01

Type of information: Completion of patient enrollment

phase: 3

Announcement: completion of patient enrollment

Company: Gensight Biologics (France)

Product: GS010- adeno-associated viral vector containing the human NADH dehydrogenase 4 gene

Action mechanism:

  • gene therapy. GS010 is a gene therapy-based single intravitreal injection in the eye targeting LHON due to the ND4 gene mutation. GS010 uses GenSight’s Mitochondrial Targeting Sequence (MTS) proprietary technology platform, which permits missing mitochondrial proteins to be shuttled into the mitochondrion, enabling the restoration of mitochondrial function.
  • GS010 has been granted Orphan Drug Designation both in the United States and in Europe.

Disease: Leber’s hereditary optic neuropathy (LHON)

Therapeutic area: Ophtalmological diseases - Genetic diseases - Rare diseases

Country: France, Germany, Italy, UK, USA

Trial details:

  • RESCUE and REVERSE are two separate randomized, double-masked, sham-controlled pivotal Phase III trials designed to evaluate the efficacy of a single intravitreal injection of GS010 (rAAV2/2-ND4) in subjects affected by LHON due to the G11778A mutation in the mitochondrial ND4 gene. The primary endpoint will measure the difference in efficacy of GS010 in treated eyes compared to sham-treated eyes based on Best Corrected Visual Acuity (BCVA), as measured with the ETDRS at 48 weeks post-injection. The patients’ Log of the Minimal Angle of Resolution, or LogMAR, scores, which are derived from the number of letters they read on the ETDRS chart, will be used for statistical purposes. Both trials have been adequately powered to evaluate a clinically relevant difference of at least 15 ETDRS letters between treated and untreated eyes adjusted to baseline. The secondary endpoints will involve the application of the primary analysis to best seeing eyes that received GS010 compared to those receiving sham, and to worse seeing eyes that received GS010 compared to those that received sham. Additionally, a categorical evaluation with a responder analysis will be evaluated, including the proportion of patients who maintain vision (< ETDRS 15L loss), the proportion of patients who gain 15 ETDRS letters from baseline and the proportion of patients with Snellen acuity of >20/200. Complementary vision metrics will include automated visual fields, optical coherence tomography, and color and contrast sensitivity, in addition to quality of life scales, bio-dissemination and the time course of immune response. (REVERSE NCT02652780 and RESCUE NCT02652767)

Latest news:

  • • On August 1, 2017, GenSight Biologics announced that enrollment in RESCUE has been successfully completed. RESCUE enrolled 37 patients with an onset of vision loss of less than 6 months. REVERSE, the second trial, completed enrollment in February 2017 of 36 patients with an onset of vision of 7-12 months. Both studies are being conducted in 7 centers in Europe and in the United States. Topline results of REVERSE at 48 weeks of follow-up are expected in Q2 2018, while RESCUE is expected to read out in Q3 2018.
  • • On February 21, 2017, GenSight Biologics announced that enrollment in REVERSE, a Phase III clinical trial of GS010 in the treatment of Leber’s Hereditary Optic Neuropathy (LHON), has been successfully completed. REVERSE enrolled 36 patients with an onset of vision loss of 7-12 months, while RESCUE, the second trial, is currently enrolling 36 patients with an onset of vision loss of less than 6 months. Both studies are being conducted in 7 centers in Europe and in the United States. Topline results of REVERSE at 48 weeks are expected at the end of Q1 2018. RESCUE is expected to complete enrollment by the end of H1 2017
  • .• On September 8, 2016, GenSight Biologics announced that regulatory agencies and ethics committees in the United States, France and the United Kingdom, have authorized a protocol amendment to include teenage patients (15-18 years) in RESCUE and REVERSE, two ongoing Phase III clinical trials of GS010 in the treatment of Leber’s Hereditary Optic Neuropathy (LHON). The Investigational New Drug (IND) Application had been cleared by the FDA in August 2015, and Clinical Trial Applications (CTAs) had been accepted in France, Germany, Italy and the United Kingdom by national agencies in the first half of 2016, allowing GenSight Biologics to initiate the two Phase III clinical trials in the US and in Europe. The initial protocols were designed to enroll adult patients, whereas this amendment now allows inclusion of patients from the age of 15. The trials are conducted in parallel in 7 centers across the United States, the UK, France, Germany and Italy. Topline results at 48 weeks are expected early 2018.
  • • On February 29, 2016, GenSight Biologics announced enrollment of the first patient in both RESCUE and REVERSE, two parallel pivotal Phase III trials with GS010 for the treatment of Leber’s Hereditary Optic Neuropathy (LHON). The pivotal trials are intended to determine whether GS010 can halt or reverse vision loss associated with LHON due to the NADH dehydrogenase 4 (ND4) mutation or be effective as prophylaxis for vision loss in an eye not yet affected. The trials will also seek to identify the therapeutic window of opportunity for treatment after onset of disease. As early intervention is potentially a major factor in maximizing therapeutic success, the two clinical trials will focus on treating patients who have manifested visual decline for up to one year. RESCUE is expected to enroll 36 patients with an onset of vision loss up to 6 months in duration, while REVERSE is expected to enroll 36 patients with an onset of vision loss ranging from 7 to 12 months in duration. GS010 will be administered as a single intravitreal injection to one eye of each subject, while the fellow eye will receive a sham procedure. At the end of the initial 48-week study period, a minimal three-year long term follow-up period will be initiated to determine the sustainability of efficacy outcomes and long-term safety of treatment. The first patient in the entire program was injected at the Doheny Eye Institute, UCLA Department of Ophthalmology, Pasadena, California (USA) as part of the REVERSE trial, while the first RESCUE trial patient was injected at Wills Eye Hospital, Philadelphia, Pennsylvania (USA). The trials will be conducted in parallel in 7 centers across the United States, the UK, France, Germany and Italy. European sites will open in the coming weeks upon final approval of regulatory agencies. Topline results at 48 weeks are expected by the end of 2017.
  • • On September 10, 2015, GenSight Biologics announced that the FDA has cleared its Investigational New Drug (IND) Application for two Phase III clinical trials of GS010 in the treatment of Leber’s Hereditary Optic Neuropathy (LHON). GenSight has also submitted a Clinical Trial Application (CTA) in certain individual European Union countries.

Is general: Yes