Safety, tolerability, and efficacy of the PD-1 agonist antibody JNJ-67484703 in adults with active rheumatoid arthritis: results of a multicenter, double-blind, placebo-controlled, randomized, multiple-dose phase Ib study

作者: Ling, Irving T. C. ; Liva, Sophia G. ; Wang, Tong ; Lakshminarayanan, Vani ; Marciniak, Stanley J. ; Orillion, Ashley ; Tikhonov, Ilia ; Noss, Erika H. ; Loza, Matthew J. ; Clarke, Stephen H.

Background::

Programmed cell death protein 1 (PD-1) is associated with the immunopathology of rheumatoid arthritis (RA). JNJ-67484703 is a humanized IgG anti-PD-1 agonist antibody.

Objectives::

To report results of a phase Ib study evaluating the safety, tolerability, and disease-related outcomes of JNJ-67484703 in adults with active rheumatoid arthritis.

Design::

A randomized, double-blind, placebo-controlled, multiple-dose, phase Ib study in adults with active RA who were inadequately controlled on conventional synthetic disease-modifying antirheumatic drugs.

Methods::

JNJ-67484703 at doses of 2 or 3 mg/kg or placebo was administered by subcutaneous injection for 10 weeks (on weeks 0, 1, 2, 4, 6, 8, and 10). Safety was assessed for the first 6 participants in the 2 mg/kg group to determine if enrollment would proceed to the 3 mg/kg dose. The primary endpoint was the proportion of participants with treatment-emergent adverse events (TEAEs). Secondary endpoints included change from baseline at week 12 in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) and circulating PD-1 + T-cell counts at the 3 mg/kg dose level only. Least squares (LS) mean difference between JNJ-67484703 groups and placebo were based on mixed-effect model for repeated measures for DAS28-CRP.

Results::

A total of 44 participants were randomized to receive JNJ-67484703 2 mg/kg ( n = 5), 3 mg/kg ( n = 25), or placebo ( n = 14); TEAEs were reported in 4 (80%), 17 (68%), and 10 (71%), respectively. None were severe in intensity, and no deaths were reported. TEAEs of infection were reported in 21% of placebo participants and 20% of those in the combined JNJ-67484703 groups. No injection-site or hypersensitivity reactions were reported. At week 12, reduction in DAS28-CRP from baseline was numerically greater in the JNJ-67484703 2 mg/kg and 3 mg/kg groups versus placebo, with a difference in LS means between the 3 mg/kg group and placebo of −0.69 (95% CI −1.55, 0.18; p = 0.117). JNJ-67484703 decreased circulating PD-1 + T cells, with the greatest effect on those with the highest baseline expression of PD-1.

Conclusion::

JNJ-67484703 was well tolerated in participants with active RA and showed evidence for biologic and clinical activity in this small, proof-of-mechanism study.

Trial registration::

ClinicalTrials.gov, NCT04985812.

项与 Anti-PD-1 agonist antibody (Meiji Seika Pharma) 相关的新闻（医药）

2023-01-16

·BioSpace

A novel anti-PD-1 agonist antibody with immunosuppressive effect discovered through joint research between Meiji Seika Pharma and the Foundation for Biomedical Research and Innovation at Kobe

TOKYO--(BUSINESS WIRE)-- Meiji Seika Pharma Co., Ltd. (Headquarters: Tokyo, Japan, President and Representative Director: Daikichiro Kobayashi) and the Foundation for Biomedical Research and Innovation at Kobe (Headquarters: Kobe, Japan, President: Tasuku Honjo, hereinafter ‘FBRI’) announce the discovery of a novel anti-PD-1 agonist monoclonal antibody, which can induce immunosuppressive effect, through their collaborative research on “Treatment of inflammatory diseases, including autoimmune diseases, through the immunosuppressive activity of PD-1” (HBI* Innovation Program) conducted at the FBRI's Dept. of Immunology, Institute of Biomedical Research and Innovation (Professor: Akio Ohta). Part of the findings from the above research was published in "Science Immunology**" issued on January 13, 2023 (Eastern Standard Time). For more information, please visit the FBRI website (URL: ). Meiji Seika Pharma and FBRI are working together to develop the above PD-1 agonist monoclonal antibody as therapeutic candidate for autoimmune diseases. PD-1 is a molecule expressed on activated lymphocytes and has the function as a suppressor of immune responses. Antibodies that inhibit the function of PD-1 (anti-PD-1 blocking antibodies) can enhance anti-tumor immunity, so that they have been applied to cancer treatment as "immune checkpoint inhibitors." Through the above joint research supervised by Program Director Tasuku Honjo, Nobel laureate in 2018, Meiji Seika Pharma and FBRI discovered the conditions necessary for inducing immunosuppression by stimulating the function of PD-1 with antibodies. "Anti-PD-1 agonist antibody" is expected to be applied as a novel therapeutic for inflammatory diseases such as autoimmune diseases caused by excessive immune reactions. Meiji Seika Pharma and FBRI continue to progress the joint research on "anti-PD-1 agonist antibody" and strive to the early contribution of this antibody as a therapeutic agent for autoimmune diseases. *: HBI: Honjo Kobe Research Center for Biomedical Innovation **: DOI: 10.1126/sciimmunol.add4947 View source version on businesswire.com: Contacts Meiji Seika Pharma Co., Ltd.: Public Relations, Corporate Development Dept. Email: pr-pharma (Please add “@meiji.com” to the end) Foundation for Biomedical Research and Innovation at Kobe: Public relations and Strategic planning group Email: kbic-pr (Please add “@fbri-kobe.org” to the end) Source: Meiji Seika Pharma Co., Ltd. View this news release online at:

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