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MTRX1011A, a humanized anti-CD4 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled study incorporating pharmacodynamic biomarker assessments.


ABSTRACT: The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the humanized anti-CD4 monoclonal antibody MTRX1011A in a randomized, double-blind placebo-controlled Phase 1 study in patients with rheumatoid arthritis (RA).In the single ascending dose (SAD) portion of the study, patients received single doses of a placebo or MTRX1011A at 0.3, 1.0, 3.5 and 7.0 mg/kg intravenously (i.v.) or 1.0 and 3.5 mg/kg subcutaneously (s.c.), followed by five weeks of evaluation. In the multi-dose (MD) portion of the study, placebo or MTRX1011A was administered weekly for eight doses at 1.5 or 3.5 mg/kg s.c., or 5 mg/kg i.v., followed by eight weeks of evaluation.MTRX1011A was well tolerated in the SAD phase up to 7 mg/kg i.v. and in the MD phase up to 1.5 mg/kg s.c.. At weekly doses of 3.5 mg/kg s.c. and 5 mg/kg i.v., a moderate pruritic papular rash was observed in some MTRX1011A-treated patients, which was considered a dose-limiting toxicity for this clinical indication. No serious adverse events occurred in any cohort. Reduction in disease activity was modest. PD assessments demonstrated that MTRX1011A induced a dose-dependent down-modulation of CD4 expression on peripheral blood CD4 T cells, CD4 receptor occupancy, increases in serum sCD4-MTRX1011A complexes and up-regulation of CD69 on T cells, but was non-depleting.The maximum tolerated dose of MTRX1011A was 1.5 mg/kg SC administered weekly. At this dose MTRX1011A did not achieve maximum PD activity expected to be required for reduction in disease activity.

SUBMITTER: Scheerens H 

PROVIDER: S-EPMC3308112 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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MTRX1011A, a humanized anti-CD4 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled study incorporating pharmacodynamic biomarker assessments.

Scheerens Heleen H   Su Zheng Z   Irving Bryan B   Townsend Michael J MJ   Zheng Yanan Y   Stefanich Eric E   Chindalore Vishala V   Bingham Clifton O CO   Davis John C JC  

Arthritis research & therapy 20111026 5


<h4>Introduction</h4>The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the humanized anti-CD4 monoclonal antibody MTRX1011A in a randomized, double-blind placebo-controlled Phase 1 study in patients with rheumatoid arthritis (RA).<h4>Methods</h4>In the single ascending dose (SAD) portion of the study, patients received single doses of a placebo or MTRX1011A at 0.3, 1.0, 3.5 and 7.0 mg/kg intravenously (i.v.) or 1.0 and 3.5 mg/k  ...[more]

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