First Author: G.Barteselli USA
Co Author(s): S. Francom J. Hopkins
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Although the efficacy of ranibizumab treatment for neovascular age-related macular degeneration (nAMD) is well-established, treatment often requires frequent monitoring and repeated intravitreal injections that pose a treatment burden to many patients, their caregivers, and healthcare providers. The ranibizumab Port Delivery System (RPDS) is a refillable, implanted device that provides sustained intravitreal release of ranibizumab between refills using a diffusion-controlled drug delivery mechanism. A phase 1 open-label study in 20 treatment-naïve patients with nAMD established proof-of-concept for RPDS. Long-Acting Delivery of ranibizumab (LADDER) is a phase 2 trial evaluating the safety and efficacy of the RPDS in patients with nAMD.
LADDER (NCT02510794) is an ongoing, phase 2, multicentre, randomized, interventional, active-treatment controlled clinical trial at approximately 55 sites in the USA.
Patients eligible for the phase 2 LADDER trial have nAMD, diagnosed within 6 months, and a documented response to intravitreal anti-vascular endothelial growth factor (VEGF) treatment. Patients are randomized to RPDS with 1 of 3 ranibizumab formulations (N=60 each) or monthly intravitreal ranibizumab 0.5 mg (N=40). The RPDS is surgically implanted in the pars plana, and refills are performed in the clinic using a customized refill needle assembly that exchanges the reservoir contents with fresh drug.
Projected enrollment of LADDER is 220 patients. The time to the first RPDS refill, according to protocol-defined refill criteria, is the primary end point. The secondary end point, change from baseline in best-corrected visual acuity (BCVA) over time, will be used to evaluate each of the RPDS arms versus monthly intravitreal ranibizumab 0.5 mg. Additional secondary outcomes include: change from baseline in central foveal thickness on spectral-domain optical coherence tomography, adverse event (AE) incidence (ocular, non-ocular, AEs of special interest), and patient-reported outcomes.
Real-world data suggest that many patients do not receive optimal treatment for nAMD, and this under-treatment in clinical practice is associated with lower visual acuity gains compared with randomized controlled clinical trials. Sustained delivery of ranibizumab via the RPDS has the potential to achieve less frequent dosing compared with anti-VEGF injections and improve on visual outcomes associated with under-treatment in clinical practice. The phase 2 LADDER trial is evaluating dosing and functional outcomes of sustained delivery of ranibizumab via the RPDS, which aims to provide longer treatment intervals than any currently available therapy.