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Georges Weissgerber, Sushanta Mallick, Esteve Travesa, Colin Hughson, Thomas Valencia, Hermann Schulze, Kyounghwa Bae, Silvia Boller, Anne Schmidt, Dominik Escher; Safety And Tolerability Of Single Escalating Doses Of Esba1008, A Single-chain Anti-vegf Antibody Fragment, In Patients With Exudative Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4641.
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Evaluation of the safety and tolerability of a single intravitreal (IVT) injection of 0.5 mg, 3 mg or 4.5 mg of ESBA1008 in the dose escalation phase of this ongoing prospective, Lucentis® (0.5 mg) controlled, single-dose ascending, double-masked, multi-center, randomized study.
Three cohorts of 7 patients of either sex ≥ 50 years of age have been sequentially enrolled. In each cohort patients have been randomized to an IVT administration in the study eye of ESBA1008 or Lucentis® in a 5:2 ratio. The first 4 patients in each cohort were dosed sequentially. Escalation to the next cohort was allowed only if the previous dose didn't meet the dose-escalation stopping criteria (targeted and serious adverse events related to ESBA1008).Study eyes were treatment-naïve. Selection criteria included a new diagnosis of exudative AMD or evidence of recent disease progression in the last 3 months, best corrected visual acuity (BCVA) between 20/40 and 20/200, evidence of subretinal fluid or retinal cystic changes with central subfield thickness of > 340 µm, presence of a primary subfoveal choroidal neovascularization (CNV) secondary to AMD, a lesion area 50% of the total lesion area. Subretinal blood, if present must have spared the fovea and must involve ≤ 50% of the lesion.
Each of 3 escalating doses of ESBA1008 have been injected in 5 eyes of 5 patients. Doses were well tolerated as assessed by the absence of study medication related targeted adverse events in the study eye within 7 (±1) days of the IVT injection (primary safety endpoint).This favorable safety and tolerability evaluation was also supported by the other ocular safety endpoints such as evaluation of study eye post-injection, BCVA, ocular signs, posterior segment abnormalities, evaluation of retina hemorrhage/detachment, evaluation of vitreal hemorrhage density and vitreous cells, intraocular pressure and eyelid/pupil responsiveness.
ESBA1008, a potent inhibitor of VEGF, was safely administered to 15 patients at doses up to 4.5 mg/eye. The well-tolerated high doses, combined with the smaller molecular size of scFv’s compared to full-length IgG or Fab fragments and the high affinity for VEGF, give ESBA1008 the potential to be administered at intervals greater than the current monthly interval, thereby reducing the treatment burden.
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