First-in-human trial of the safety, pharmacokinetics and immunogenicity of a PEGylated anti-CD40L antibody fragment (CDP7657) in healthy individuals and patients with systemic lupus erythematosus

Lupus
A TocoianR Oliver

Abstract

The objective of this paper is to investigate the safety, pharmacokinetics (PK) and immunogenicity of CDP7657, a PEGylated anti-CD40L antibody fragment, in healthy individuals and patients with systemic lupus erythematosus (SLE). This randomized, double-blind, single-dose, dose-escalation phase I study consisted of two parts. In part 1, 28 healthy individuals received CDP7657 IV (0.004-5 mg/kg) or placebo. In part 2, 17 patients with SLE received CDP7657 IV (5-60 mg/kg) or placebo. The CDP7657:placebo ratio was 3:1. Adverse events (AEs) were reported by 76% of healthy individuals and 100% of patients with SLE treated with CDP7657; most were mild or moderate in intensity. Two healthy individuals reported serious AEs (SAEs), one of which was considered treatment related (infusion-related reaction; 5 mg/kg cohort). One patient with SLE (60 mg/kg cohort) experienced three SAEs, one of which was considered treatment related (herpes zoster infection). No thromboembolic events were reported. CPD7657 exposure increased in a dose-proportional manner. Low anti-CDP7657 antibody titres were detected in the majority of CDP7657-treated participants with no apparent impact on the PK of CDP7657. Single doses of CDP7657 showed predictable PK in...Continue Reading

References

Mar 19, 1996·Proceedings of the National Academy of Sciences of the United States of America·K GerritseE Claassen
May 3, 2003·Annals of the New York Academy of Sciences·Anne DavidsonJayashree Sinha
Jul 10, 2004·Clinical and Diagnostic Laboratory Immunology·Dimitris DaoussisStamatis-Nick C Liossis
Nov 3, 2004·The Journal of Clinical Investigation·Hong Jiang, Leonard Chess
Mar 18, 2008·British Journal of Haematology·Vivek L PatelJames B Bussel
Jun 30, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Liza Robles-CarrilloAli Amirkhosravi
Feb 2, 2011·The Journal of Allergy and Clinical Immunology·Cagri Yildirim-Toruner, Betty Diamond
Apr 14, 2012·International Journal of Rheumatology·Mariana PostalSimone Appenzeller
Aug 31, 2012·Expert Opinion on Drug Delivery·Ricardo P GarayPascal Richette
Jan 11, 2013·Arthritis Research & Therapy·Valentin Marian, Jennifer H Anolik
Oct 30, 2013·Nature Reviews. Rheumatology·Wen Xiong, Robert G Lahita

❮ Previous
Next ❯

Citations

Mar 8, 2016·Expert Opinion on Investigational Drugs·Mariana PostalTimothy B Niewold
Apr 1, 2016·Expert Opinion on Biological Therapy·Mo Yin Mok, Yehuda Shoenfeld
Jun 15, 2016·Current Rheumatology Reports·Helena Hiemisch Lobo BorbaRoberto Pontarolo
Jul 3, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Peng ZhangShaoyi Jiang
Jul 13, 2016·Rheumatology·Stinne GreisenBent Deleuran
Sep 25, 2016·Joint, Bone, Spine : Revue Du Rhumatisme·Estibaliz LazaroChristophe Richez
Nov 1, 2016·Science Translational Medicine·Tamer I MahmoudRachel Ettinger
Oct 25, 2016·Transplantation·Akiko FurukawaQizhi Tang
Jan 18, 2017·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S C KimA B Adams
Mar 5, 2016·Folia medica·Zornitsa G KamenarskaLyubomir A Dourmishev
Jan 7, 2020·Médecine sciences : M/S·Nathalie BonnefoyBernard Vanhove
Feb 29, 2020·Immunological Medicine·Wen Shi Lee, Olga Amengual
Oct 21, 2017·Arthritis Research & Therapy·Sandro Félix PerazzioLuis Eduardo Coelho Andrade
Jul 19, 2017·Current Rheumatology Reports·Marc ScherlingerPatrick Blanco
Aug 12, 2017·Expert Review of Clinical Immunology·Matthias CassiaDavid Jayne
Feb 1, 2017·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A W Thomson, M B Ezzelarab
Feb 1, 2020·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Kalliopi KlavdianouAntonis Fanouriakis
Nov 18, 2020·International Journal of Molecular Sciences·Steffen DaubAndreas Daiber
Oct 14, 2020·British Journal of Clinical Pharmacology·Yasuhiro TsudaJürgen Steffgen
Oct 31, 2020·Frontiers in Immunology·Bingyi YangQianjin Lu
Mar 7, 2021·La Revue de médecine interne·G VialP Duffau

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme-linked immunosorbent assay

Clinical Trials Mentioned

NCT01093911

Software Mentioned

Phoenix
WinNonlin

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Kansenshōgaku zasshi. The Journal of the Japanese Association for Infectious Diseases
T KusabaT Mayumi
Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases
Mauricio Restrepo Escobar
© 2021 Meta ULC. All rights reserved