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J Jill Hopkins, Carl D Regillo, Aaron Osborne, Steven F Francom, Giulio Barteselli; Sustained Delivery of Ranibizumab: The LADDER Trial of the Ranibizumab Port Delivery System. Invest. Ophthalmol. Vis. Sci. 2016;57(12):530.
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© ARVO (1962-2015); The Authors (2016-present)
The use of anti-VEGF intravitreal (ITV) injections to treat retinal diseases including neovascular age-related macular degeneration (nAMD) is well-established. However, treatment often requires frequent ITV injections, which can be burdensome. The phase 2 LADDER trial is evaluating the Ranibizumab (RBZ) Port Delivery System (RPDS), a refillable implanted device, in patients with nAMD. The RPDS uses a diffusion-controlled drug delivery mechanism to provide sustained ITV release of RBZ between refills. LADDER follows a phase 1 open-label study of the RPDS in 20 treatment-naïve patients with nAMD, which established proof-of-concept for RPDS safety and efficacy.
LADDER is a phase 2 multicenter, randomized, interventional, active-treatment controlled clinical trial, with the primary endpoint 9 months after last patient randomization. Eligible patients have subfoveal nAMD, diagnosed within 6 months, with documented response to ITV anti-VEGF treatment. Patients are randomized 3:3:3:2 to RPDS with 1 of 3 RBZ formulations (N=60 each) or monthly ITV RBZ 0.5 mg (N=40). The RPDS is surgically implanted in the pars plana (subconjunctival), and refills are performed in the clinic using a customized refill needle that exchanges the reservoir contents with fresh drug.
LADDER anticipates enrolling 220 patients at up to 55 US sites. The primary objective is to evaluate the time to the first RPDS refill according to protocol-defined refill criteria. The key secondary endpoint, change from baseline in BCVA, will be used to test the non-inferiority (NI) of each of the RPDS arms vs monthly ITV RBZ 0.5 mg using a 4 letter NI margin. Other secondary outcomes include: mean change in BCVA from baseline (BL) to Month 9, mean average change in BCVA through Month 9, mean change from BL in central foveal thickness on SD-OCT, and adverse event (AE) incidence (ocular, non-ocular, AEs of special interest).
Sustained delivery has the potential to reduce the treatment burden associated with anti-VEGF injections for patients and improve visual outcomes associated with under-treatment in clinical practice. LADDER is an ongoing phase 2 study evaluating dosing and functional outcomes with sustained delivery of RBZ via the RPDS.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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