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Abstract：
BACKGROUND: The MIMIX platform is a novel microneedle array patch (MAP) characterized by slowly dissolving microneedle tips that deploy into the dermis following patch application. We describe safety, reactogenicity, tolerability and immunogenicity for MIMIX MAP vaccination against influenza.
METHODS: The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 μg or 7.5 μg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a computer program to create a randomization scheme with a block size of 3. Post-treatment follow-up was approximately 180 days. Primary safety outcomes included the incidence of study product related serious adverse events and unsolicited events within 180 days, solicited application site and systemic reactogenicity through 7 days after administration and solicited application site erythema and/or pigmentation 14, 28, 56 and 180 days after administration. Immunogenicity outcomes included antibody titers and percentage of seroconversion (SCR) and seroprotection (SPR) rates determined by the hemagglutination inhibition (HAI) assay. Exploratory outcomes included virus microneutralization (MN) titers, durability and breadth of the immune response. The trial was registered with ClinicalTrials.gov, number NCT06125717.
RESULTS: Between July 7, 2022 and March 13, 2023 45 participants were randomized to a treatment group. One participant was lost to follow up in the 15 μg group and 1 participant withdrew from the 7.5 μg dose group. Safety analyses included n = 15 per group, immunogenicity analyses included n = 14 for the 15 μg and 7.5 μg treatment groups and n = 15 for the placebo group. No SAEs were reported in any of the treatment groups. All treatment groups reported solicited local events within 7 days after vaccination, with mild (Grade 1) erythema being the most frequent symptom reported. Other local symptoms reported included mostly mild (Grade 1) induration/swelling, itching, pigmentation, skin flaking, and tenderness. Within 7 days after vaccination, 2 participants (4.4%) reported moderate (Grade 2) erythema, 1 participant (2.2%) reported moderate (Grade 2) induration/swelling, and 1 participant (2.2%) reported moderate (Grade 2) itching. There was an overall reduction in erythema and pigmentation reported on Days 15, 29, 57, and 180 among all treatment groups. Systemic symptoms reported within 7 days after vaccination, included mild (Grade 1) fatigue reported among all treatment groups, and mild (Grade 1) headache reported by 1 participant in the 7.5 μg treatment group. No study drug related severe symptoms were reported in the study. Group mean fold rises in HAI titers ranged between 8.7 and 12-fold, SCRs were >76% and SPRs were >92% for both VX-103 dose groups thereby fulfilling serological criteria established by the EMA and FDA for seasonal influenza vaccines. Longitudinal assessments demonstrate persistence of the immune response through at least Day 180.
CONCLUSIONS: The MIMIX MAP platform is safe, well tolerated and elicits robust antibody responses.
METHODS: The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 μg or 7.5 μg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a computer program to create a randomization scheme with a block size of 3. Post-treatment follow-up was approximately 180 days. Primary safety outcomes included the incidence of study product related serious adverse events and unsolicited events within 180 days, solicited application site and systemic reactogenicity through 7 days after administration and solicited application site erythema and/or pigmentation 14, 28, 56 and 180 days after administration. Immunogenicity outcomes included antibody titers and percentage of seroconversion (SCR) and seroprotection (SPR) rates determined by the hemagglutination inhibition (HAI) assay. Exploratory outcomes included virus microneutralization (MN) titers, durability and breadth of the immune response. The trial was registered with ClinicalTrials.gov, number NCT06125717.
RESULTS: Between July 7, 2022 and March 13, 2023 45 participants were randomized to a treatment group. One participant was lost to follow up in the 15 μg group and 1 participant withdrew from the 7.5 μg dose group. Safety analyses included n = 15 per group, immunogenicity analyses included n = 14 for the 15 μg and 7.5 μg treatment groups and n = 15 for the placebo group. No SAEs were reported in any of the treatment groups. All treatment groups reported solicited local events within 7 days after vaccination, with mild (Grade 1) erythema being the most frequent symptom reported. Other local symptoms reported included mostly mild (Grade 1) induration/swelling, itching, pigmentation, skin flaking, and tenderness. Within 7 days after vaccination, 2 participants (4.4%) reported moderate (Grade 2) erythema, 1 participant (2.2%) reported moderate (Grade 2) induration/swelling, and 1 participant (2.2%) reported moderate (Grade 2) itching. There was an overall reduction in erythema and pigmentation reported on Days 15, 29, 57, and 180 among all treatment groups. Systemic symptoms reported within 7 days after vaccination, included mild (Grade 1) fatigue reported among all treatment groups, and mild (Grade 1) headache reported by 1 participant in the 7.5 μg treatment group. No study drug related severe symptoms were reported in the study. Group mean fold rises in HAI titers ranged between 8.7 and 12-fold, SCRs were >76% and SPRs were >92% for both VX-103 dose groups thereby fulfilling serological criteria established by the EMA and FDA for seasonal influenza vaccines. Longitudinal assessments demonstrate persistence of the immune response through at least Day 180.
CONCLUSIONS: The MIMIX MAP platform is safe, well tolerated and elicits robust antibody responses.
摘要：
背景:MIMIX平台是一种新型微针阵列贴片(MAP),其特征在于缓慢溶解在贴片应用后展开到真皮中的微针尖端。我们描述安全，反应原性,针对流感的MIMIXMAP疫苗接种的耐受性和免疫原性。
方法：该试验是1期，探索性，人类第一，平行随机，rater,参与者,研究分析师盲，加拿大的安慰剂对照研究。45名健康参与者(18至39岁，包括包容性）以1：1：1的比例随机接受15μg或7.5μg的H1N1流感疫苗，或通过MIMIXMAP递送至掌侧前臂的安慰剂。统计学家使用计算机程序创建块大小为3的随机化方案。治疗后随访约180天。主要安全性结果包括180天内研究产品相关严重不良事件和未经请求的事件的发生率。在给药后7天征求的应用部位和全身反应原性以及在给药后14、28、56和180天征求的应用部位红斑和/或色素沉着。免疫原性结果包括通过血凝抑制(HAI)测定确定的抗体滴度和血清转化(SCR)百分比和血清保护(SPR)率。探索性结果包括病毒微中性化(MN)滴度，免疫反应的持久性和广度。该试验已在ClinicalTrials.gov注册，编号NCT06125717。
结果：在2022年7月7日至2023年3月13日之间，45名参与者被随机分配到治疗组。15μg组一名参与者失访，7.5μg剂量组一名参与者退出。安全性分析包括每组n=15，免疫原性分析包括15μg和7.5μg治疗组的n=14,安慰剂组的n=15。在任何治疗组中没有报告SAE。所有治疗组在接种疫苗后7天内报告征求当地事件，轻度（1级）红斑是最常见的症状。报告的其他局部症状主要包括轻度（1级）硬结/肿胀，瘙痒,色素沉着,皮肤剥落，和温柔。接种疫苗后7天内，2名参与者（4.4%）报告中度（2级）红斑，1名参与者（2.2％）报告中度（2级）硬结/肿胀，1名参与者（2.2％）报告中度（2级）瘙痒。在所有治疗组中,在第15、29、57和180天报告红斑和色素沉着总体减少。疫苗接种后7天内报告的全身症状，包括所有治疗组报告的轻度（1级）疲劳，7.5μg治疗组中1名参与者报告的轻度（1级）头痛。研究中未报告与研究药物相关的严重症状。HAI滴度的组平均倍数上升在8.7到12倍之间，对于两个VX-103剂量组,SCR>76%,SPR>92%,从而满足EMA和FDA为季节性流感疫苗建立的血清学标准。纵向评估表明免疫应答持续到至少第180天。
结论：MIMIXMAP平台是安全的，耐受性良好，并引发强烈的抗体反应。
方法：该试验是1期，探索性，人类第一，平行随机，rater,参与者,研究分析师盲，加拿大的安慰剂对照研究。45名健康参与者(18至39岁，包括包容性）以1：1：1的比例随机接受15μg或7.5μg的H1N1流感疫苗，或通过MIMIXMAP递送至掌侧前臂的安慰剂。统计学家使用计算机程序创建块大小为3的随机化方案。治疗后随访约180天。主要安全性结果包括180天内研究产品相关严重不良事件和未经请求的事件的发生率。在给药后7天征求的应用部位和全身反应原性以及在给药后14、28、56和180天征求的应用部位红斑和/或色素沉着。免疫原性结果包括通过血凝抑制(HAI)测定确定的抗体滴度和血清转化(SCR)百分比和血清保护(SPR)率。探索性结果包括病毒微中性化(MN)滴度，免疫反应的持久性和广度。该试验已在ClinicalTrials.gov注册，编号NCT06125717。
结果：在2022年7月7日至2023年3月13日之间，45名参与者被随机分配到治疗组。15μg组一名参与者失访，7.5μg剂量组一名参与者退出。安全性分析包括每组n=15，免疫原性分析包括15μg和7.5μg治疗组的n=14,安慰剂组的n=15。在任何治疗组中没有报告SAE。所有治疗组在接种疫苗后7天内报告征求当地事件，轻度（1级）红斑是最常见的症状。报告的其他局部症状主要包括轻度（1级）硬结/肿胀，瘙痒,色素沉着,皮肤剥落，和温柔。接种疫苗后7天内，2名参与者（4.4%）报告中度（2级）红斑，1名参与者（2.2％）报告中度（2级）硬结/肿胀，1名参与者（2.2％）报告中度（2级）瘙痒。在所有治疗组中,在第15、29、57和180天报告红斑和色素沉着总体减少。疫苗接种后7天内报告的全身症状，包括所有治疗组报告的轻度（1级）疲劳，7.5μg治疗组中1名参与者报告的轻度（1级）头痛。研究中未报告与研究药物相关的严重症状。HAI滴度的组平均倍数上升在8.7到12倍之间，对于两个VX-103剂量组,SCR>76%,SPR>92%,从而满足EMA和FDA为季节性流感疫苗建立的血清学标准。纵向评估表明免疫应答持续到至少第180天。
结论：MIMIXMAP平台是安全的，耐受性良好，并引发强烈的抗体反应。
