Safety and Tolerability. Please refer to the Investigator’s Brochure for a detailed discussion of safety findings for studies in healthy subjects, oncology, CKD, and PH patients with bardoxolone methyl.
Safety and Tolerability. The safety data from all patients will be assessed on an ongoing basis. Safety and tolerability will be assessed using Dose limiting Toxicities (DLTs), adverse events (AEs), physical examination, ECGs, LVEF, laboratory and vital sign data as recorded on the CRF.
Safety and Tolerability. Safety reporting in clinical investigations of medical devices shall be performed in line with the requirements of the Regulation (EU) 2017/745 – Medical Device Regulation (MDR) Article 80(2). The sponsor shall report, without delay to all Member States in which the clinical investigation is being conducted, all of the following by means of the electronic system referred to in MDR Article 73:
Safety and Tolerability. OPT-302 has demonstrated acceptable safety and tolerability up to 2 mg administered by repeat IVT dosing every 4 weeks either alone or in combination with the anti-VEGF-A therapy, ranibizumab (0.5 mg), in a Phase 1 first in human (FIH) study (OPT-302-1001) in 51 patients with nAMD. The Phase 1 study consisted of two parts: Part 1 was an open-label, sequential dose escalation (n=20; 0.3, 1 or 2 mg OPT-302 with 0.5 mg ranibizumab, or 2 mg OPT-302 monotherapy, in 4 cohorts of 5 patients each); Part 2 was a randomized dose expansion (n=31, 2 mg OPT-302 with 0.5 mg ranibizumab [n=23] or 2 mg OPT-302 monotherapy [n=8]). All study drugs were administered by IVT injection for three consecutive dosing cycles at 4 weekly intervals. Of the 51 patients enrolled, 19 (37%) were male, 32 (63%) were female, 10 (20%) had diabetes mellitus and 25 (49%) were treatment naïve, while 26 (51%) had received ≥ 3 prior IVT injections of anti-VEGF-A therapy. No dose-limiting toxicities (DLTs) were observed with OPT-302 at any IVT dose level up to 2 mg either in combination with anti-VEGF-A therapy or as a monotherapy, and the MTD was not reached. In addition, there was no evidence of OPT-302 related immunogenicity after IVT administration of OPT-302 doses up to 2.0 mg/eye. Overall, 100% of evaluable participants at Week 12 (n=49) maintained BCVA, defined as ≤15 letter loss from baseline. In addition, changes from baseline in anatomic measures (CST) on SD-OCT through to week 12, demonstrated no adverse safety signals in treatment naïve patients and those who showed a sub-optimal response to prior anti-VEGF-A therapy. In summary, OPT-302 was well tolerated at doses up to 2 mg when administered by repeat intravitreal injections once every 4 weeks, either in combination with anti-VEGF-A therapy (0.5 mg ranibizumab) or as a monotherapy.
