close

Clinical Trials

Date: 2015-10-02

Type of information: Results

phase: 2b

Announcement: results

Company: Sylentis (Spain)

Product: bamosiran (SYL040012)

Action mechanism: RNAi

Disease: ocular hypertension associated with glaucoma

Therapeutic area: Ophtalmological diseases

Country: Spain, Estonia, Germany, USA

Trial details:

  • SYLTAG is a multicenter, international, dose-finding Phase II, double masked, randomized and controlled study that investigated the efficacy and safety of bamosiran by measuring the IOP during the day after 28 days of treatment (one drop per day in each eye) in patients with open-angle glaucoma or ocular hypertension compared to the active control, timolol given twice a day. The study has enrolled 180 patients from 21 centers across Europe and the US, which were distributed in 5 groups of about 36 patients each to receive four different doses of bamosiran (0.375%, 0.75%, 1.125% and 1.5%) or timolol (0.5%), respectively. The primary efficacy endpoint of the study was to determine the most effective drug dose to reduce IOP during the day, at day 14 and 28. The secondary endpoints included comparison of efficacy against timolol and quality of life measurements (using the Glaucoma Quality of Life questionnaire (GQL-15). The trial also studied the safety profile and tolerability of the treatments by means of measuring ocular discomfort, clinical ophthalmological values, systemic tolerability and adverse events. (NCT02250612)

Latest news:

  • • On October 2, 2015, Sylentis announced results of a dose-finding Phase II study, SYLTAG, for the novel RNAi therapeutic bamosiran in patients with open-angle glaucoma or ocular hypertension. The SYLTAG study, which includes 184 patients with a baseline IOP greater than or equal to 23 mm Hg, evaluates the efficacy and safety of four doses 0,375% (150 micrograms); 0,75% (300 micrograms); 1,125% (450 micrograms) y 1,5% (600 micrograms) given once a day for 28 days. The comparator group received timolol (0.5%), given twice a day. After 28 days of treatment, the four groups treated with bamosiran (0.375%, 0.75%, 1.125% y 1.5%) showed a similar reduction in the IOP. Bamosiran did not meet the secondary objective of demonstrating non-inferiority compared to timolol for any of the doses in the total patient population; however, at dose 1.125% (450 micrograms) it showed non-inferiority in patients with baseline IOP greater than or equal to 25 mm Hg and it was non-inferior compared to timolol in this patient group. The results showed excellent tolerability of bamosiran in all the treated groups with a very low hyperhemia (less than 8%). • On July 17, 2014, Grupo Zeltia has announced that Sylentis, a pioneer in the research and development of new drugs based on gene silencing through RNA interference (RNAi), has been authorised by the Estonian authorities to commence a Phase IIb trial with bamosiran (SYL040012) for the treatment of glaucoma and ocular hypertension. This is the first authorisation in the list of countries where the trial is to be conducted, and it enables patient enrolment to commence. This trial is part of the development of bamosiran as a topical drug for the treatment of ocular hypertension and glaucoma. It will make it possible to ascertain the optimal dose with a view to progressing to Phase III trials.
  • • On June 7, 2013, Zeltia has announces that its subsidiary Sylentis has attained the primary endpoint of the Phase IIa clinical trial with its compound SYL040012. This trial evaluated the safety of SYL040012 on the eye surface and its effect on intraocular pressure following a daily dose for 14 days in patients with ocular hypertension or openangle glaucoma.The three doses analysed in the trial were well-tolerated both locally (cornea and conjunctiva) and systemically, and they reduced intraocular pressure. The 300 microgram dose of SYL040012 was found to produce a statistically significant reduction in intraocular pressure with respect to the placebo. The next clinical trial will be planned once all of the trial's variables have been analysed.
  • * On June 13, 2012, Sylentis  has received authorisation from the Spanish and Estonian regulatory agencies to commence Phase II clinical trials with SYL040012 for treating ocular hypertension associated with glaucoma. This is Sylentis's fourth clinical trial using RNAi technology. SYL040012 is its first compound to enter clinical trials, evidencing the company's commitment to developing innovative compounds to treat eye diseases.  In preclinical trials with SYL040012, the siRNAs administered topically to treat ocular hypertension associated with open-angle glaucoma have proven effective in vivo. These trials concluded that the model of transient hypertension induced by fluid overload is valid for evaluating the efficacy of different drugs on glaucoma since it does not produce alterations in the various ocular structures. These trials showed that pretreatment with SYL040012 prevents the induced increase in intraocular pressure in this ocular hypertension model. The prophylactic effect of this compound is greater than the one described previously in this model with the drugs currently used for treating glaucoma, such as timolol or Xalatan.
  • The company has another compound, SYL1001, which has completed a Phase I clinical trial in eye discomfort associated with dry eye syndrome.

Is general: Yes