Younis Brima M, Wiggins Rebecca, Khalil Eltahir A G, Osman Mohamed, Santoro Francesco, Sonnati Chiara, Keding Ada, Novedrati Maria, Montesi Giorgio, Noureldein Ali, Elmukashfi Elmukashfi T A, Mustafa Ala Eldin, Alamin Mohammed, Saeed Mohammed, Salman Khalid, Suliman Ahmed J, Musa Amin E A, Layton Alison M, Lacey Charles J N, Kaye Paul M, Musa Ahmed M
Department of Clinical Pathology & Immunology, Institute of Endemic Diseases, University of Khartoum, Khartoum 11111, Sudan.
York Biomedical Research Institute, Hull York Medical School, University of York, Heslington, York YO10 5DD, UK.
Mol Ther Methods Clin Dev. 2024 Jul 30;32(3):101310. doi: 10.1016/j.omtm.2024.101310. eCollection 2024 Sep 12.
In a recent phase 2a clinical trial, the candidate leishmaniasis vaccine ChAd63-KH was shown to be safe and immunogenic in Sudanese patients with post kala-azar dermal leishmaniasis (PKDL). However, its value as a stand-alone therapeutic was unknown. To assess the therapeutic efficacy of ChAd63-KH, we conducted a randomized, double-blind, placebo-controlled phase 2b trial (ClinicalTrials.gov: NCT03969134). Primary outcomes were safety and efficacy (≥90% improvement in clinical disease). Secondary outcomes were change in severity grade and vaccine-induced immune response. 86 participants with uncomplicated PKDL of ≥6 month duration were randomized to receive ChAd63-KH (7.5 × 10 viral particles, once by the intramuscular route) or placebo. 75 participants (87%) completed the trial as per protocol. No severe or serious adverse events were observed. At day 90 post-vaccination, 6/40 (15%) and 4/35 (11%) participants in the vaccine and placebo groups, respectively, showed ≥90% clinical improvement (risk ratio [RR] 1.31 [95% confidence interval (CI), 0.40-4.28], = 0.742). There were also no significant differences in PKDL severity grade between study arms. Whole-blood transcriptomic analysis identified transcriptional modules associated with interferon responses and monocyte and dendritic cell activation. Thus, a single vaccination with ChAd63-KH showed no therapeutic efficacy in this subset of Sudanese patients with PKDL.
在最近一项2a期临床试验中，候选利什曼病疫苗ChAd63-KH在患有黑热病后皮肤利什曼病（PKDL）的苏丹患者中显示出安全性和免疫原性。然而，其作为单一治疗方法的价值尚不清楚。为了评估ChAd63-KH的治疗效果，我们进行了一项随机、双盲、安慰剂对照的2b期试验（ClinicalTrials.gov：NCT03969134）。主要结局指标是安全性和疗效（临床疾病改善≥90%）。次要结局指标是严重程度等级的变化和疫苗诱导的免疫反应。86名患有病程≥6个月的单纯性PKDL的参与者被随机分配接受ChAd63-KH（7.5×10个病毒颗粒，通过肌肉注射途径给药一次）或安慰剂。75名参与者（87%）按照方案完成了试验。未观察到严重或严重不良事件。在接种疫苗后第90天，疫苗组和安慰剂组分别有6/40（15%）和4/35（11%）的参与者显示出≥90%的临床改善（风险比[RR]1.31[95%置信区间（CI），0.40-4.28]，P = 0.742）。研究组之间PKDL严重程度等级也没有显著差异。全血转录组分析确定了与干扰素反应以及单核细胞和树突状细胞激活相关的转录模块。因此，在这一苏丹PKDL患者亚组中，单次接种ChAd63-KH未显示出治疗效果。
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