Center for Interstitial Lung Diseases, Department of Medicine and Laboratory Medicine, University of Washington, Seattle, WA, USA.
Pulmonary and Critical Care Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
Respir Res. 2022 May 21;23(1):129. doi: 10.1186/s12931-022-02047-0.
Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151-202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks.
Patients who completed the randomized PRM-151-202 study period were eligible for the OLE, during which all patients received rhPTX-2, having started rhPTX-2 (i.e., crossed from placebo) or continued rhPTX-2 after Week 28. rhPTX-2 was administered in 28-week cycles, with 10 mg/kg intravenous infusions (60 min) on Days 1, 3, and 5 in the first week of each cycle, then one infusion every 4 weeks up to Week 128. The OLE primary objective was to assess the long-term safety and tolerability of rhPTX-2. Other outcomes included FVC, 6MWD, and patient-reported outcomes (descriptive analysis).
All 111 patients who completed the randomized period entered the OLE (n = 37 started rhPTX-2; n = 74 continued rhPTX-2); 57 (51.4%) completed to Week 128. The treatment-emergent adverse event (TEAE) profile was consistent with the randomized period, with the majority of TEAEs graded mild or moderate. Serious TEAEs occurred in 47 patients (42.3%), most frequently IPF (n = 11; 9.9%), pneumonia (n = 7; 6.3%), and acute respiratory failure (n = 3; 2.7%). Three patients underwent lung transplantation. Most serious TEAEs (and all 14 fatal events) were considered unrelated to rhPTX-2 treatment. For patients starting vs continuing rhPTX-2, mean (95% confidence interval) changes from baseline to Week 128 were, respectively, - 6.2% (- 7.7; - 4.6) and - 5.7% (- 8.0; - 3.3) for percent predicted FVC and - 36.3 m (- 65.8; - 6.9) and - 28.9 m (- 54.3; - 3.6) for 6MWD; however, conclusions were limited by patient numbers at Week 128.
Long-term treatment (up to 128 weeks) with rhPTX-2 was well tolerated in patients with IPF, with no new safety signals emerging in the OLE. The limited efficacy data over 128 weeks may suggest a trend towards a treatment effect. Trial registration NCT02550873; EudraCT 2014-004782-24.
在为期 28 周、安慰剂对照、随机的 PRM-151-202 研究中，重组人 pentraxin-2（rhPTX-2）显著降低了特发性肺纤维化（IPF）患者用力肺活量（FVC）预计百分比的下降，并稳定了 6 分钟步行距离（6MWD）。二期 PRM-151-202 研究开放标签扩展（OLE）的中期（76 周）数据显示，rhPTX-2 治疗具有持续的安全性和疗效。在此，我们展示了 rhPTX-2 治疗的整个 128 周的长期 OLE 安全性和疗效数据。
完成随机 PRM-151-202 研究期的患者有资格参加 OLE，在此期间所有患者均接受 rhPTX-2 治疗，起始 rhPTX-2（即从安慰剂转为 rhPTX-2）或在第 28 周后继续 rhPTX-2。rhPTX-2 以 28 周为一个周期给药，每个周期的第一周连续 3 天（第 1、3 和 5 天）给予 10mg/kg 的静脉输注（60 分钟），然后每 4 周输注一次，直到第 128 周。OLE 的主要目的是评估 rhPTX-2 的长期安全性和耐受性。其他结果包括 FVC、6MWD 和患者报告的结局（描述性分析）。
所有完成随机期的 111 例患者（n=37 例起始 rhPTX-2；n=74 例继续 rhPTX-2）进入 OLE；57 例（51.4%）完成了第 128 周。治疗出现的不良事件（TEAE）与随机期一致，大多数 TEAEs 为轻度或中度。47 例患者（42.3%）发生严重 TEAEs，最常见的是 IPF（n=11；9.9%）、肺炎（n=7；6.3%）和急性呼吸衰竭（n=3；2.7%）。3 例患者接受了肺移植。大多数严重 TEAEs（和所有 14 例死亡事件）被认为与 rhPTX-2 治疗无关。对于起始 vs 继续 rhPTX-2 的患者，从基线到第 128 周的平均（95%置信区间）变化分别为，分别为 -6.2%（-7.7；-4.6）和-5.7%（-8.0；-3.3）对于预测百分比的 FVC 和-36.3 m（-65.8；-6.9）和-28.9 m（-54.3；-3.6）对于 6MWD；然而，由于第 128 周的患者人数有限，因此结论受到限制。
在特发性肺纤维化患者中，rhPTX-2 的长期治疗（长达 128 周）耐受良好，在 OLE 中未出现新的安全性信号。128 周以上的有限疗效数据可能表明存在治疗效果的趋势。试验注册 NCT02550873；EudraCT 2014-004782-24。
