Evaluation of safety and clinical activity of multiple doses of the anti-CD80 monoclonal antibody, galiximab, in patients with moderate to severe plaque psoriasis

• Published in: Clinical immunology (Orlando, Fla.) Vol. 111; no. 1; pp. 28 - 37
• Main Authors: Gottlieb, Alice B, Kang, Sewon, Linden, Kenneth G, Lebwohl, Mark, Menter, Alan, Abdulghani, Ahsan A, Goldfarb, Michael, Chieffo, Nicole, Totoritis, Mark C
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-04-2004; Elsevier
• Subjects: Adult; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Biological and medical sciences; Dermatology; Drug Administration Schedule; Female; Galiximab; Humans; Immunohistochemistry; Injections, Intravenous; Keratinocytes - metabolism; Keratinocytes - pathology; Male; Medical sciences; Middle Aged; PASI; Psoriasis; Psoriasis - drug therapy; Psoriasis. Parapsoriasis. Lichen; Skin - immunology; Skin - metabolism; Skin - pathology; Treatment Outcome; Galiximab; APCs; PASI; TCR; CDC; Psoriasis; AE; MHC; ICAM-1; mRNA; PGA; AUC; PSS; PtGA; CTLA-4; ADCC; Multiple dose; Human; Immunopathology; Skin disease; Immunology; Activity; B7.1 molecule; Monoclonal antibody; Costimulatory molecule
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2004.01.006

Background: Reduction in lesional, activated T cells induces improvement in psoriatic plaques. Galiximab (IDEC-114), an IgG
1 anti-CD80 antibody, binds to CD80, a costimulatory molecule involved in T-cell activation.
Objective: A Phase I/II, multidose, multischedule, dose-finding study of galiximab to evaluate safety, pharmacokinetics, and clinical activity was conducted in 35 patients with moderate to severe plaque psoriasis.
Methods: Seven cohorts of five patients received galiximab intravenously on three different schedules at different dose levels.
Results: Adverse events (AEs) commonly occurred as mild and self-limiting. Improvements were observed in most cohorts without evidence of a dose response in Psoriasis Area and Severity Index (50% or greater reduction in PASI score in 40% of patients), Physician's Global Psoriasis Assessment (PGA rating of Good or above in 57% of patients), and Psoriasis Severity Scale (PSS, baseline mean of 7.6 decreased by Study Day 127 to 5.0). An association was observed between reduction in CD3
+ cell count in histologic studies and reduction in PASI score. No antibodies to galiximab were detected.
Conclusion: Galiximab appears to be safe and well tolerated with preliminary evidence of clinical and histologic response.