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Brian Berger, Pamela Garzone, Ivana Gunderson, Philip Fanning, Gilbert Wong, Kai Liao, Steven Hua, John Lin; Phase I, Masked, Placebo-Controlled, Single and Multiple Ascending Intravenous Dose Studies Evaluating Systemic and Ocular Safety, Tolerability, and Visual Acuity Effects of RN6G (PF-04382923) in Subjects with Dry, Age-Related Macular Degeneration (ARMD). Invest. Ophthalmol. Vis. Sci. 2013;54(15):4505.
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To examine the safety (systemic and ocular) and tolerability of single and multiple ascending intravenous (IV) doses of RN6G (PF-04382923), a humanized IgG2Δa monoclonal antibody and to explore the effects of RN6G on best corrected visual acuity (BCVA) by ETDRS, low luminance BCVA (LLBCVA) and contrast sensitivity (CS).
In the Phase 1, first-in-human (FIH) study, 54 adult men and women with dry ARMD were assigned to a cohort (n=9) and randomized to receive either a single intravenous (IV) dose of RN6G (0.3 mg/kg to 40 mg/kg) or placebo (PBO), 2:1 ratio of active drug to PBO, within a cohort. Safety, BCVA and LLBCVA were done at specified intervals with the last observation at week 24. In the multiple ascending dose (MAD) study, 24 adult men and women with advanced dry ARMD or geographic atrophy were enrolled into one of 3 cohorts (5 mg/kg, 10 mg/kg, or 15 mg/kg) and were randomized to active drug or PBO (3:1). Six IV treatments were administered monthly followed by safety observations over five months. BCVA, LLBCVA and CS were tested monthly through week 44.
In the FIH study, 45 subjects (83.3%) had at least one treatment (Tx) emergent adverse event (TEAE); 28 subjects (51.9%) had at least one AE related to Tx. Headache was the most common AE followed by iritis. There was no dose response in either frequency or severity of AEs. All systemic and ocular AEs observed were considered mild to moderate in severity. There were no withdrawals due to AEs. One serious AE (SAE) unrelated to Tx was reported. BCVA was reduced in 2 subjects; 1 received RN6G and 1 received PBO. In the MAD study, 94% (17/18) of subjects receiving RN6G and 100% (6/6) receiving PBO reported TEAEs. The most frequently reported systemic TEAEs were infections (38%) and nervous system disorders (29%). Ocular TEAEs were reported in 58% of subjects and blepharitis was the most frequently reported TEAE. Preliminary BCVA, LLBCVA and CS results were unchanged. Two SAEs that were considered not related to Tx were reported.
RN6G (PF-0438293) was safe and well tolerated by all subjects in Phase I. No effects on BCVA , LLBCVA or CS were observed. Based on the safety and tolerability profile, a Phase II study was initiated in July 2012.
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