Safety, pharmacokinetics and pharmacodynamics of single rising doses of BI 655064, an antagonistic anti-CD40 antibody in healthy subjects: a potential novel treatment for autoimmune diseases.
Purpose: The CD40-CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and lupus nephritis. The safety, pharmacokinetics and pharmacodynamics of BI 655064, a novel humanised antagonistic anti-CD40 monoclonal antibody, were i...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 74; no. 2; pp. 161 - 170 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Feb2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=127247543&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 127247543 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Feb2018 vid: 74 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 127247543 127247543 144051744 127247543 10.1007/s00228-017-2362-8 127247543 ppf: 161 ppct: 9 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Safety, pharmacokinetics and pharmacodynamics of single rising doses of BI 655064, an antagonistic anti-CD40 antibody in healthy subjects: a potential novel treatment for autoimmune diseases. aug: au: Albach, Fredrik Wagner, Frank Hüser, Andreas Igel, Julia Joseph, David Hilbert, James Schoelch, Corinna Padula, Steven Steffgen, Jürgen affil: Charité Research Organisation GmbH , Berlin Germany sug: subj: Antibodies, Monoclonal Pharmacodynamics Antibodies, Monoclonal Adverse Effects Autoimmune Diseases Drug Therapy Human Male Randomized Controlled Trials Pharmacokinetics Arthritis, Rheumatoid Drug Therapy Lupus Erythematosus, Systemic Drug Therapy Lupus Nephritis Drug Therapy Male ab: Purpose: The CD40-CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and lupus nephritis. The safety, pharmacokinetics and pharmacodynamics of BI 655064, a novel humanised antagonistic anti-CD40 monoclonal antibody, were investigated in this first-in-human trial. Methods: Healthy male subjects ( n = 72) were randomised 3:1, within each BI 655064 dose group, to single intravenous (IV; 0.2-120 mg) or subcutaneous (SC; 40-120 mg) doses of BI 655064 or placebo. Safety, plasma exposure, CD40 receptor occupancy and CD40L-induced CD54 upregulation were assessed over 12 weeks. Results: Adverse events (AEs) were reported in 43% of subjects ( n = 31). Frequency and intensity of AEs were generally similar between BI 655064 and placebo and showed no dose relationship. The most frequent AEs were headache and nasopharyngitis. One mild rash and one local reaction occurred with SC BI 655064; two serious AEs were reported, both judged unrelated to BI 655064. Pharmacokinetic evaluation demonstrated a more than proportional increase in plasma exposure relative to BI 655064 dose, with a terminal half-life between 4 h and 4 days IV and approximately 5 days SC; doses ≥ 20 mg IV and 120 mg SC showed > 90% CD40 receptor occupancy and inhibition of CD54 upregulation, which lasted 7 days in the 120 mg IV and SC groups. Conclusions: Single doses up to 120 mg BI 655064 IV and SC were well tolerated and showed a high potential to block the CD40-CD40L pathway, supporting further clinical development of BI 655064 in patients with autoimmune disease. Trial registration: Identifier: NCT01510782 pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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