目的：一项 3 期、多中心、随机、双盲、安慰剂对照、平行分组试验，旨在评估特泽鲁单抗在成人和青少年中重度、未控制的哮喘中的长期安全性和耐受性。

DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma.

机构信息

Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK.

Late Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.

出版信息

Respir Res. 2020 Oct 21;21(1):279. doi: 10.1186/s12931-020-01541-7.

DOI:10.1186/s12931-020-01541-7

PMID:33087119

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7576983/

Abstract

BACKGROUND

Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. The efficacy, safety and oral corticosteroid-sparing potential of tezepelumab are being investigated in two ongoing, phase 3, randomized, double-blind, placebo-controlled studies (NAVIGATOR [NCT03347279] and SOURCE [NCT03406078]). DESTINATION (NCT03706079) is a long-term extension (LTE) of these studies.

METHODS

DESTINATION is a randomized, double-blind, placebo-controlled LTE study in adults (18-80 years old) and adolescents (12-17 years old) with severe, uncontrolled asthma who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. The study population will comprise patients who complete the 52- and 48-week NAVIGATOR and SOURCE studies, respectively. Patients who were randomized to receive tezepelumab 210 mg every 4 weeks (Q4W) in either predecessor study will continue to receive this regimen for 1 year; those who were previously randomized to receive placebo will be re-randomized (1:1) to receive either tezepelumab 210 mg Q4W or placebo for 1 year. Patients will receive their prescribed controller medications throughout DESTINATION and study physicians will have the opportunity to down- or up-titrate dosage of these medications, if appropriate. The primary objective is to evaluate the long-term safety and tolerability of tezepelumab over 104 weeks (inclusive of the treatment period of either predecessor study). The secondary objective is to assess the long-term effect of tezepelumab on asthma exacerbations. Patients recruited from SOURCE will be followed up post-treatment for 12 weeks. Patients recruited from NAVIGATOR who complete 100 weeks of tezepelumab treatment will be eligible for either 12 weeks of follow-up or a 36-week extended follow-up during which the clinical benefit of tezepelumab after treatment cessation will be investigated.

DISCUSSION

DESTINATION will evaluate the long-term safety, tolerability and efficacy of tezepelumab versus placebo with continued dosing for up to 2 years. DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma.

TRIAL REGISTRATION

NCT03706079 (ClinicalTrials.gov). Registered 15 October 2018.

摘要

背景

特泽佩鲁单抗是一种人源化单克隆抗体，可阻断上皮细胞细胞因子胸腺基质淋巴细胞生成素的活性。特泽佩鲁单抗的疗效、安全性和口服皮质类固醇节省潜力正在两项正在进行的 3 期、随机、双盲、安慰剂对照研究（NAVIGATOR[NCT03347279]和 SOURCE[NCT03406078]）中进行研究。DESTINATION（NCT03706079）是这些研究的长期扩展（LTE）。

方法

DESTINATION 是一项在接受中至高剂量吸入皮质类固醇和至少一种其他控制器药物治疗的严重、未控制的哮喘成人（18-80 岁）和青少年（12-17 岁）中进行的随机、双盲、安慰剂对照 LTE 研究，伴有或不伴有口服皮质类固醇。研究人群将包括完成 NAVIGATOR 和 SOURCE 研究 52 周和 48 周的患者。在前一项研究中随机接受特泽佩鲁单抗 210mg 每 4 周（Q4W）治疗的患者将继续接受该方案治疗 1 年；以前随机接受安慰剂的患者将重新随机（1:1）接受特泽佩鲁单抗 210mg Q4W 或安慰剂治疗 1 年。患者将在 DESTINATION 期间接受其规定的控制器药物治疗，并且研究医生将有机会根据需要下调或上调这些药物的剂量。主要目的是评估特泽佩鲁单抗在 104 周（包括前一项研究的治疗期）内的长期安全性和耐受性。次要目的是评估特泽佩鲁单抗对哮喘恶化的长期影响。从 SOURCE 招募的患者将在治疗后随访 12 周。从 NAVIGATOR 招募并完成 100 周特泽佩鲁单抗治疗的患者将有资格接受 12 周随访或 36 周扩展随访，在此期间将研究特泽佩鲁单抗治疗停止后的临床获益。