PRGN-2012基因治疗成人复发性呼吸道乳头状瘤病：一项关键的1/2期临床试验

IF 38.7 1区医学 Q1 CRITICAL CARE MEDICINE

Lancet Respiratory Medicine Pub Date : 2025-01-21 DOI:10.1016/s2213-2600(24)00368-0

Scott M Norberg, Janet Valdez, Scott Napier, Meg Kenyon, Erin Ferraro, Melissa Wheatley, Laura Parsons-Wandell, Stacey L Doran, Amy Lankford, Helen Sabzevari, Douglas E Brough, Jeffrey Schlom, James L Gulley, Clint T Allen

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引用次数: 0

摘要

背景：复发性呼吸道乳头状瘤病（RRP）是由慢性感染6型或11型人乳头状瘤病毒（HPV）引起的一种罕见的衰弱疾病。乳突状瘤在空气消化道中发展，导致明显的声音障碍和气道阻塞。目前还没有系统性的治疗方法。我们的目的是评估PRGN-2012在推荐的2期剂量治疗的成年RRP患者中的安全性和临床活性。方法这是一项单中心、单臂、1/2期试验。年龄在18岁及以上的RRP成年患者在治疗前1年内需要3次或更多的干预，在手术切除疾病后第1天、第15天、第43天和第85天接受PRGN-2012辅助治疗。主要结局指标是完全缓解率，定义为治疗后12个月内不需要干预以控制RRP的患者百分比。安全性结果包括治疗相关的不良事件。该研究已在ClinicalTrials.gov注册（NCT04724980）。从2021年3月16日至2023年6月1日，38名患者入组并接受了为期12周的治疗。在35名接受推荐的5×1011颗粒单位2期剂量治疗的患者中，35名患者中有18名（51%）患者完全缓解（95% CI 34-69），中位完全缓解持续时间尚未达到。不良事件为轻度，包括1-2级注射部位反应（35例中34例[97%]）、疲劳（35例中28例[80%]）、发冷（35例中25例[71%]）和发热（35例中24例[69%]）。prgn -2012治疗导致51%的患者完全缓解，并且是安全的。基于这些积极的关键研究结果，计划向美国食品和药物管理局（FDA）申请生物制剂许可，将PRGN-2012定位为FDA批准的成人RRP患者的药物治疗。资助国家卫生研究院。

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PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: a pivotal phase 1/2 clinical trial

Background

Recurrent respiratory papillomatosis (RRP) is a rare debilitating condition caused by chronic infection with human papillomavirus (HPV) type 6 or 11. Papillomas develop in the aerodigestive tract, leading to significant voice disturbance and airway obstruction. No systemic treatment currently exists. We aimed to assess the safety and clinical activity of PRGN-2012 in adult patients with RRP treated at the recommended phase 2 dose.

Methods

This was a single-centre, single-arm, phase 1/2 trial. Adult patients aged 18 years or older with RRP who required three or more interventions in the 1 year before treatment received adjuvant PRGN-2012 on day 1 following surgical debulking of disease, and on days 15, 43, and 85. Primary outcome measure was complete response rate, defined as the percentage of patients who did not require an intervention to control RRP in the 12 months after treatment. Safety outcomes included treatment-related adverse events. This study is registered ClinicalTrials.gov (NCT04724980).

Findings

From March 16, 2021, to June 1, 2023, 38 patients were enrolled and received the 12-week treatment course. Among the 35 patients treated at the recommended phase 2 dose of 5×10¹¹ particle units, 18 (51%) of 35 patients had a complete response (95% CI 34–69) with the median duration of complete response yet to be reached. Adverse events were mild and included grades 1–2 injection site reaction (34 [97%] of 35), fatigue (28 [80%] of 35), chills (25 [71%] of 35), and fever (24 [69%] of 35).

Interpretation

PRGN-2012 treatment resulted in complete response in 51% of the patients treated and was safe. Based on these positive pivotal study results, a biologics license application to the US Food and Drug Administration (FDA) is planned, positioning PRGN-2012 to be an FDA-approved medical treatment for adult patients with RRP.

Funding

National Institutes of Health.

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来源期刊

Lancet Respiratory Medicine RESPIRATORY SYSTEM-RESPIRATORY SYSTEM

CiteScore

87.10

自引率

0.70%

发文量

572

期刊介绍： The Lancet Respiratory Medicine is a renowned journal specializing in respiratory medicine and critical care. Our publication features original research that aims to advocate for change or shed light on clinical practices in the field. Additionally, we provide informative reviews on various topics related to respiratory medicine and critical care, ensuring a comprehensive coverage of the subject. The journal covers a wide range of topics including but not limited to asthma, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), tobacco control, intensive care medicine, lung cancer, cystic fibrosis, pneumonia, sarcoidosis, sepsis, mesothelioma, sleep medicine, thoracic and reconstructive surgery, tuberculosis, palliative medicine, influenza, pulmonary hypertension, pulmonary vascular disease, and respiratory infections. By encompassing such a broad spectrum of subjects, we strive to address the diverse needs and interests of our readership.