Budigalimab, an anti-PD-1 inhibitor, for people living with HIV-1: a randomized, placebo-controlled phase 1b study.

Budigalimab is an investigational humanized anti-PD-1 monoclonal antibody.

Budigalimab是一种正在研究中的人源化抗PD-1单克隆抗体。

Multiple intravenous (IV) low doses of budigalimab (Stage 1: 2 mg n = 10, 10 mg n = 10, placebo n = 5, two doses every 4 weeks; Stage 2: 10 mg n = 11, placebo n = 5, four doses every 2 weeks (Q2W)) were assessed in people living with HIV (PLWH; n = 41) in a randomized, double-blind, multicenter, placebo-controlledphase 1 study with an analytical treatment interruption (ATI) to identify an efficacious regimen with a favorable safety profile in PLWH.

在一项随机、双盲、多中心、安慰剂对照的1期研究中，评估了多次静脉注射（IV）低剂量的budigalimab（第1阶段：2毫克n=10，10毫克n=10，安慰剂n=5，每4周两次；第2阶段：10毫克n=11，安慰剂n=5，每2周四次（Q2W）），以确定在HIV感染者（PLWH；n=41）中具有良好安全性和耐受性的有效治疗方案，研究中包括了分析性治疗中断（ATI）。

The primary endpoints were safety, tolerability and pharmacokinetics.

主要终点是安全性、耐受性和药代动力学。

Demographics and baseline characteristics were balanced across treatment groups, except for sex, which was mostly male.

各治疗组的基线特征和人口统计学数据均衡，除了性别，其中男性占多数。

All participants identified as cisgender.

所有参与者均认同为顺性别。

Budigalimab was well tolerated for up to 44 weeks, with 29 of 41 participants experiencing an adverse event(AE), including 2 participants who each experienced one grade 1 reversible immune-related AE (thyroiditis, hyperthyroidism).

布地格利单抗在最多44周的治疗期间耐受性良好，41名参与者中有29人出现不良事件（AE），包括2名参与者各自经历了一次1级可逆的免疫相关不良事件（甲状腺炎、甲状腺功能亢进）。

Three grade 3 AEs were reported by two participants and one serious AE by one participant; none were deemed related to treatment.

三名参与者报告了三次3级不良事件，一名参与者报告了一次严重不良事件；这些均未被认为与治疗有关。

IV budigalimab 10 mg Q2W resulted in a slight accumulation of drug in serum, with concentrations remaining above the estimated concentration required for near-complete (>95%) PD-1 receptor saturation on CD8+ T cells for ~10 weeks in peripheral blood.

IV budigalimab 10 mg Q2W导致血清中药物轻微积累，浓度在约10周内保持在估计浓度以上，该浓度足以在周围血流中实现接近完全（>95%）PD-1受体在CD8+ T细胞上的饱和。

In an exploratory efficacy analysis of a 12-week ATI initiated with the first of four 10 mg Q2W doses, 6 of 11 participants experienced a delayed rebound with a relatively low viral peak and/or off-ART viral control (<200 copies ml-1) for ≥6 weeks during ATI, with 2 sustaining ART-free viral control to study end (204-252 days).

在一项为期12周的ATI（抗逆转录病毒治疗中断）探索性疗效分析中，首次使用四次10 mg Q2W剂量后，11名参与者中有6名经历了延迟反弹，表现为相对较低的病毒峰值和/或在ATI期间的ART（抗逆转录病毒治疗）病毒控制（<200 copies ml-1）持续≥6周，其中2名持续到研究结束（204-252天）无需ART的病毒控制。

The study achieved prespecified endpoints, supporting further evaluation of budigalimab in PLWH in a phase 2 study.

该研究达到了预定的终点，支持在2期研究中进一步评估PLWH中的budigalimab。

ClinicalTrials.gov identifier: NCT04223804 .

ClinicalTrials.gov注册号：NCT04223804。