Recombinant human pentraxin-2 (RHPTX-2;PRM-151) for idiopathic pulmonary fibrosis: Study design of starscape, a phase iii randomized double blind placebo controlled trial

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing, interstitial pneumonia which ultimately leads to an irreversible loss of lung function and respiratory compromise. The anti-fibrotic agents, pirfenidone and nintedanib have been shown to slow the rate of decline in forced vital capacity (FVC) but, neither treatment halts disease progression. Pentraxin-2 plays important biologically relevant roles in wound repair and prevention of fibrosis. Pentraxin-2, inhibits monocyte differentiation into pro-fibrotic fibrocytes and pro-inflammatory macrophages. Plasma pentraxin-2 concentrations are reduced in patients with IPF and correlate with disease severity. Recombinant human pentraxin-2 (rhPTX-2;also known as PRM-151) was evaluated for its therapeutic potential within a phase II trial (NCT02550873). This trial demonstrated statistically significant and clinically meaningful outcomes of rhPTX-2 treatment in patients with IPF. Here we report the phase III study design to further evaluate these findings. METHODS: STARSCAPE (NCT04552899) is a phase III, multi-center, randomized, double-blind, placebo controlled trial. 658 patients with IPF will be randomized (1:1) to receive either intravenous rhPTX-2 or matching placebo administered on Days 1, 3, 5 and every 4 weeks thereafter through 48 weeks. The primary endpoint is absolute change from baseline to Week 52 in FVC [mL]. The key secondary endpoint is absolute change from baseline to Week 52 in 6-minute walk distance. Eligible patients are 40-85 years, with a documented diagnosis of IPF confirmed centrally by high resolution computed tomography scan (and lung biopsy if available). Patients must demonstrate FVC ≥ 45%, FEV1/FVC ratio > 0.70 and DLCO ≥ 30% and ≤ 90% during screening. Patients are permitted to take background therapy with nintedanib or pirfenidone. Initiating a global phase III trial during the COVID-19 pandemic brings unique and unprecedented challenges. A large number of countries and sites will be included in order to mitigate potential regional recruitment challenges that may arise during the pandemic. In addition, SARS-CoV-2 serology testing will be conducted to allow exploratory analyses on the impact of COVID-19 on lung function parameters in patients with IPF. CONCLUSIONS: rhPTX-2 has demonstrated preliminary evidence of clinical efficacy on top of approved standard of care. The phase III STARSCAPE trial aims to confirm the therapeutic potential of rhPTX-2 through evaluation of a broad range of efficacy, safety, quality of life, pharmacokinetic and biomarker assessments over 52 weeks. Patients that complete this 52-week trial may be eligible to enroll into an open label extension trial.