Bispecific 10E8.4/iMab broadly neutralizing antibody in people with or without HIV-1: a partially randomized phase 1 trial.

Here we conducted a first-in-human, phase 1 trial of the bispecific 10E8.4/iMab antibody, which consists of a 10E8.4 arm binding the HIV-1 envelope glycoprotein membrane-proximal external region and an ibalizumab (iMab) arm binding the human CD4 molecule. 10E8.4/iMab was administered intravenously (IV) or subcutaneously (SC).

在这里，我们进行了一项针对双特异性10E8.4/iMab抗体的人体一期试验，该抗体由10E8.4臂和ibalizumab（iMab）臂组成，分别结合HIV-1包膜糖蛋白膜近外部区域和人类CD4分子。10E8.4/iMab通过静脉（IV）或皮下（SC）给药。

Safety/tolerability within 2 weeks of 10E8.4/iMab administration (primary outcome) and the pharmacokinetics (PK), antiviral activity, induction of anti-10E8.4/iMab antibodies, longitudinal CD4+ and CD8+ T cell counts and long-term safety (secondary outcomes) were evaluated. 54 participants living with HIV (PLWH) or without HIV (PLWoH) received 10E8.4/iMab or placebo.

在10E8.4/iMab给药后2周内的安全性/耐受性（主要结果）以及药物动力学（PK）、抗病毒活性、诱导抗-10E8.4/iMab抗体、CD4+和CD8+ T细胞计数的纵向变化以及长期安全性（次要结果）得到了评估。共有54名HIV感染者（PLWH）或未感染HIV者（PLWoH）接受了10E8.4/iMab或安慰剂治疗。

In arm 1, PLWoH received 10E8.4/iMab 0.3 mg kg-1 IV, 1 mg kg-1 SC, or 1 mg kg-1 IV (n = 3 each).

在第一组中，未感染HIV者（PLWoH）接受了10E8.4/iMab静脉注射0.3 mg kg-1，皮下注射1 mg kg-1，或静脉注射1 mg kg-1（每组n = 3）。

In arm 2, PLWoH received 10E8.4/iMab 3 mg kg-1 IV, 10 mg kg-1 IV or 30 mg kg-1 IV (n = 6 each).

在第2组中，PLWoH接受了10E8.4/iMab 3 mg kg-1 静脉注射，10 mg kg-1 静脉注射或30 mg kg-1 静脉注射（每组n = 6）。

In arms 3/3a, PLWH received 10E8.4/iMab 10 mg kg-1 IV (n = 3) or 30 mg kg-1 IV (n = 6).

在第3/3a组中，PLWH接受了10E8.4/iMab 10 mg kg-1 静脉注射（n = 3）或30 mg kg-1 静脉注射（n = 6）。

In arm 4, PLWoH were randomized to receive 10E8.4/iMab or placebo 2.5 mg kg-1 SC or 10 mg kg-1 SC (n = 9 each).

在第4组中，PLWoH被随机分配接受10E8.4/iMab或安慰剂2.5 mg kg-1皮下注射或10 mg kg-1皮下注射（每组n = 9）。

Participants in arms 1-3 were not randomized.

第1-3组的参与者没有进行随机分配。

No treatment-related serious adverse events (AEs) or AEs ≥ grade 3 were reported.

未报告与治疗相关的严重不良事件（AEs）或3级及以上的不良事件。

The most common solicited AEs were tenderness (10/54, 18.5%), fatigue (18/54, 33.3%) and headache (12/54, 22.2%).

最常见的主动报告的不良事件是压痛（10/54，18.5%），疲劳（18/54，33.3%）和头痛（12/54，22.2%）。

Related grade 2 local and systemic solicited AEs occurred in one and six participants, respectively.

相关2级局部和全身不良事件分别发生在一名和六名参与者中。

Three of nine PLWH developed a generalized rash 8-12 days after infusion that resolved within 9-16 days.

九名PLWH中有三人在接受输液后8-12天发展为全身性皮疹，皮疹在9-16天内消退。

The primary objective of the study to evaluate the safety/tolerability of 10E8.4/iMab was met.

该研究的主要目标是评估10E8.4/iMab的安全性和耐受性，这一目标已达成。

These data support further study of 10E8.4/iMab to expand HIV treatment and prevention options.

这些数据支持进一步研究10E8.4/iMab，以扩大HIV治疗和预防的选项。

ClinicalTrials.gov: NCT03875209 .

ClinicalTrials.gov: NCT03875209 .