Phase I clinical trial dataset: naked DNA SARS-CoV-2 Omicron BA.2 booster vaccine Alveavax-v1.2 against Janssen Ad26.COV2.S comparator, NCT05844202

Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (Alveavax-v1.2): Results of a first-in-human, open-label, active-controlled, randomized dose-finding study of intradermal and subcutaneous application in primary Ad26.COV2.S vaccinated healthy individuals.

We conducted a Phase I open-label, active-controlled, randomized safety and dose-finding study for the naked DNA Omicron BA.2 booster vaccine Alveavax-v1.2. Healthy participants previously immunized with a single Janssen Ad26.COV2.S vaccine were recruited from seven non-hospital study sites in South Africa. Primary outcome was safety and tolerability on day 28 after vaccination; secondary endpoints were humoral immunogenicity, clinical efficacy and success rate of intradermal (ID) injections. A central randomization system allocated participants into the groups in blocks ranging from 1 to 5: low dose - 0.5 mg ID; standard dose - 2 mg ID; high dose - 8 mg (4 ID of 2 mg each); subcutaneous injection - 8 mg; control - Janssen Ad26.COV2.S booster as a single intramuscular injection. All analyses were based on a modified Intent-To-Treat (mITT) population. ClinicalTrials.gov Identifier: NCT05844202.

As this was a phase I study, all data were analyzed descriptively without a formal statistical hypothesis and sample sizes were not based on a statistical power calculation. Figure 1 illustrates the participants included in the safety and immunogenicity analyses.

The safety population was the set of all study participants who were administered with a dose of the vaccine candidate. Participants were grouped as treated. All enrolled participants who received a study vaccine and experienced at least one post-baseline immunogenicity readout comprised the modified intent-to-treat (mITT) population. Missing or non- evaluable measurements were not replaced. The mITT and Safety populations were identical. The mITT population was used instead of the per protocol population for the immunogenicity analyses as the differences to the Janssen control were small and the former included more participants.

Categorical variables were summarized as frequencies and percentages. Continuous variables were summarized using descriptive statistics (number of participants with an observation [n], mean, standard deviation [SD], median, and range). Where partial dates (missing day or missing day and month) were recorded on the electronic case report form (CRF) and where these could not be resolved by queries, dates were estimated for the purpose of calculating durations. Statistical analysis was performed using SAS® software (version 9.4 or higher; SAS Institute Inc., USA). AEs were coded using MedDRA version 25.1. Coding included the system organ class and preferred term.

关于Alveavax-v1.2型DNA SARS-CoV-2疫苗（奥米克隆BA.2加强剂）的安全性及免疫原性：一项针对初级Ad26.COV2.S疫苗接种健康个体，首次进行的人体、开放标签、主动对照、随机剂量探索研究的结果，涉及皮内和皮下注射。本研究旨在对裸露DNA奥米克隆BA.2型加强疫苗Alveavax-v1.2进行一期开放标签、主动对照、随机安全性及剂量探索研究。招募了曾在南非七个非医院研究地点接种过单剂Janssen Ad26.COV2.S疫苗的健康参与者。主要终点为疫苗接种后第28天的安全性及耐受性；次要终点包括体液免疫原性、临床疗效及皮内（ID）注射的成功率。中央随机化系统将参与者分配到1至5个分组块中：低剂量组-皮内0.5毫克；标准剂量组-皮内2毫克；高剂量组-8毫克（每个皮内注射2毫克，共4次）；皮下注射组-8毫克；对照组-作为单次肌内注射的Janssen Ad26.COV2.S加强剂。所有分析均基于修改后的意向治疗（mITT）人群。ClinicalTrials.gov识别符：NCT05844202。

鉴于本为I期研究，所有数据均进行描述性分析，未采用正式的统计假设，样本量亦未基于统计功效计算。图1展示了纳入安全性和免疫原性分析的研究参与者。安全性人群是指接受疫苗候选药物剂量的一组研究参与者。参与者被分为治疗组。所有入组并接受研究疫苗且至少有一次基线后免疫原性读数的参与者构成了修改后的意向治疗（mITT）人群。缺失或不可评估的测量值未进行替换。mITT人群与安全性人群相同。由于与Janssen对照组的差异较小，且mITT人群包含更多参与者，因此免疫原性分析中使用了mITT人群而非按方案人群。

分类变量以频率和百分比进行汇总。连续变量使用描述性统计（观察参与者数量 [n]、平均值、标准差 [SD]、中位数和范围）进行汇总。在电子病例报告表（CRF）上记录的部分日期（缺失日期或缺失日期和月份）无法通过查询解决时，为了计算持续时间，对这些日期进行了估算。统计分析使用SAS®软件（版本9.4或更高；SAS Institute Inc.，美国）进行。不良事件（AEs）使用MedDRA版本25.1进行编码。编码包括系统器官类别和首选术语。