抗 COVID-19 高免疫静脉注射免疫球蛋白（C-IVIG）治疗严重 COVID-19 患者的 II/III 期临床试验：一项随机对照试验的研究方案。

Phase II/III trial of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy in severe COVID-19 patients: study protocol for a randomized controlled trial.

机构信息

Dow College of Biotechnology, Dow University of Health Sciences, Karachi, Pakistan.

Department of Biotechnology, University of Karachi, Karachi, Pakistan.

出版信息

Trials. 2022 Nov 8;23(1):932. doi: 10.1186/s13063-022-06860-2.

DOI:10.1186/s13063-022-06860-2

PMID:36348476

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9643954/

Abstract

BACKGROUND

COVID-19 poses a global health challenge with more than 325 million cumulative cases and above 5 million cumulative deaths reported till January 17, 2022, by the World Health Organization. Several potential treatments to treat COVID-19 are under clinical trials including antivirals, steroids, immunomodulators, non-specific IVIG, monoclonal antibodies, and passive immunization through convalescent plasma. The need to produce anti-COVID-19 IVIG therapy must be continued, alongside the current treatment modalities, considering the virus is still mutating into variants of concern. In this context, as the present study will exploit pooled diversified convalescent plasma collected from recovered COVID-19 patients, the proposed hyperimmune Anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy would be able to counter new infectious COVID-19 variants by neutralizing the virus particles. After the successful outcome of the phase I/II clinical trial of C-IVIG, the current study aims to further evaluate the safety and efficacy of single low dose C-IVIG in severe COVID-19 patients for its phase II/III clinical trial.

METHODS

This is a phase II/III, adaptive, multi-center, single-blinded, randomized controlled superiority trial of SARS-CoV-2 specific polyclonal IVIG (C-IVIG). Patients fulfilling the eligibility criteria will be block-randomized using a sealed envelope system to receive either 0.15 g/Kg C-IVIG with standard of care (SOC) or standard of care alone in 2:1 ratio. The patients will be followed-up for 28 days to assess the primary and secondary outcomes.

DISCUSSION

This is a phase II/III clinical trial evaluating safety and efficacy of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) in severe COVID-19 patients. This study will provide clinical evidence to use C-IVIG as one of the first-line therapeutic options for severe COVID-19 patients.

TRIAL REGISTRATION

Registered at clinicaltrial.gov with NCT number NCT04891172 on May 18, 2021.

摘要

背景

截至 2022 年 1 月 17 日，世界卫生组织报告全球累计新冠肺炎确诊病例超过 3.25 亿例，累计死亡病例超过 500 万例。目前正在临床试验中评估多种治疗新冠肺炎的潜在方法，包括抗病毒药物、类固醇、免疫调节剂、非特异性静脉注射免疫球蛋白、单克隆抗体和通过恢复期血浆进行被动免疫。考虑到该病毒仍在变异为令人关注的变体，除了当前的治疗方法外，还需要继续生产抗 COVID-19 静脉注射免疫球蛋白治疗。在这种情况下，由于本研究将利用从康复的 COVID-19 患者中收集的多样化的混合恢复期血浆，因此所提议的高免疫抗 COVID-19 静脉免疫球蛋白（C-IVIG）治疗将能够通过中和病毒颗粒来对抗新的传染性 COVID-19 变体。在 C-IVIG 的 I/II 期临床试验成功后，本研究旨在进一步评估单低剂量 C-IVIG 在严重 COVID-19 患者中的安全性和疗效，以便进行 II/III 期临床试验。

方法

这是一项针对 SARS-CoV-2 特异性多克隆 IVIG（C-IVIG）的 II/III 期、适应性、多中心、单盲、随机对照优效性试验。符合入选标准的患者将使用密封信封系统按块随机分组，接受 0.15 g/Kg C-IVIG 联合标准治疗（SOC）或仅接受标准治疗，比例为 2:1。患者将随访 28 天，以评估主要和次要结局。