{
  "abstract": "Background JL18008 is a genetically engineered fusion protein of human serum albumin (HSA) and IL-7 designed for clinical use with an enhanced half-life. The preclinical data showed that JL18008 recovered T cell counts in lymphocytopenic animal models. This study is a first-in-human, randomized, double-blind, placebo-controlled phase 1 trial to assess the pharmacokinetic (PK), pharmacodynamic (PD), safety, tolerability, and immunogenicity profiles of JL18008 for supporting the development of clinical indications in patients with T cell-compromised infectious or malignant diseases.Methods JL18008 was administered at 1, 5, 10, 20, 40, and 70 μg/kg doses via a single-dose intramuscular injection (i.m.) in a dose-escalation study. Subjects receiving placebo or JL18008 treatment at 1:3 ratio in each dose level were randomly enrolled. Forty healthy subjects were assessed for T cell and lymphocyte subtype, cytokines, PK, toxicity, tolerability, and immunogenicity during 56 days of clinical observation.Results The single-dose JL18008 i.m. administration showed that the half-life was 20.3 to 97.8 hours based on the different dose levels. JL18008 increased the absolute lymphocyte, CD4 +, and CD8+ T cell counts in a dose-dependent manner, which showed a transient drop of cell counts on Day 1-3 after dosing, and then these cells increased and remained at the apex from Day 7 to Day 21. Of note, JL18008 at 20, 40, and 70 μg/kg doses showed 37% to 180% increase of absolute cell counts in different cell subtypes until the last visit time at Day 56. CD4+ T cell count increased more than CD8+ T cell count based on the increased CD4/CD8 T cell ratio at the same dose level. No significant change in B cell count was observed. The anti-drug antibody (ADA) positive rate was 23.3% but ADA did not affect PK and PD results. Most AEs were less than grade 2. Injection site reaction was the most common AE, which resolved spontaneously without treatment. Blood triglyceride abnormality was the only grade 3 AE observed, in 1 subject receiving 70 μg/kg of JL18008. The dose range of 20 to 70 μg/kg is anticipated to be the effective dose range for recovery of T cells in lymphocytopenia cases based on PD effects.Conclusions JL18008 was safe and well-tolerated at all dose levels of administration. Its significant PD effects support the clinical use in patients with lymphocytopenia or in combination with T cell-based immunotherapy.Trial Registration CTR20241578Ethics Approval The phase 1 trial of JL18008 in healthy subjects was approved by the Center for Drug Evaluation (CDE) of National Medical Products Administration (NMPA) in China and conducted at the Clinical Pharmacology Research Center, Peking Union Medical College Hospital, after ethical approval by the Institutional Review Board. All subjects provided written informed consents before participating in this study. All study procedures were performed in accordance with the Declaration of Helsinki and the International Conference on Harmonisation guidelines for Good Clinical Practice.",
  "authors": [
    {
      "affiliations": [
        "Jecho Laboratories, Frederick, MD, USA"
      ],
      "name": "Sarah Johnson"
    },
    {
      "affiliations": [
        "Peking Union Medical College Hospital, Beijing, China"
      ],
      "name": "Rui Chen"
    },
    {
      "affiliations": [
        "Peking Union Medical College Hospital, Beijing, China"
      ],
      "name": "Qian Zhao"
    },
    {
      "affiliations": [
        "Jecho Institute, Shanghai, China"
      ],
      "name": "Changying Hao"
    },
    {
      "affiliations": [
        "Jecho Institute, Shanghai, China"
      ],
      "name": "Jingjing Song"
    },
    {
      "affiliations": [
        "Jecho Institute, Shanghai, China"
      ],
      "name": "Hailong Zhang"
    },
    {
      "affiliations": [
        "Jecho Institute, Shanghai, China"
      ],
      "name": "Xixi Zhao"
    },
    {
      "affiliations": [
        "Peking Union Medical College Hospital, Beijing, China"
      ],
      "name": "Wei Tian"
    },
    {
      "affiliations": [
        "Peking Union Medical College Hospital, Beijing, China"
      ],
      "name": "Jiali Zhou"
    },
    {
      "affiliations": [
        "Jecho Institute, Shanghai, China"
      ],
      "name": "Gang Li"
    },
    {
      "affiliations": [
        "Jecho Institute, Shanghai, China"
      ],
      "name": "Jianwei Zhu"
    },
    {
      "affiliations": [
        "Jecho Laboratories, Frederick, MD, USA"
      ],
      "name": "Xiaodong Xiao"
    },
    {
      "affiliations": [
        "Jecho Institute, Shanghai, China"
      ],
      "name": "Liang Zhang"
    },
    {
      "affiliations": [
        "Peking Union Medical College Hospital, Beijing, China"
      ],
      "name": "Xiaohong Han"
    }
  ],
  "title": "1339 A randomized, double-blind, placebo-controlled, dose-escalated, first-in-human study to assess the safety, tolerability, and T cell replenishment of JL18008, a long-acting IL-7, in healthy subjects",
  "uid": "43ebc7a5-8119-544a-85e2-4cae0dbf7aba"
}