Article Text

PDF
FRI0156 Pharmacokinetics of ABT-122, A Dual TNF- and IL-17A-Targeted DVD-IG™, After Single Dosing in Healthy Volunteers and Multiple Dosing in Subjects with Rheumatoid Arthritis
  1. G.F. Ahmed,
  2. S. Goss,
  3. P. Jiang,
  4. H. Mansikka,
  5. R.J. Padley,
  6. A.A. Othman
  1. AbbVie Inc, North Chicago, United States

Abstract

Background ABT-122 is a novel dual-variable domain immunoglobulin that specifically neutralizes both TNF alpha and interleukin-17A, with the dual neutralization aimed to achieve greater clinical response in immune-mediated inflammatory diseases than blocking either cytokine alone.

Objectives This work characterized the pharmacokinetics of ABT-122 after single [Intravenous (IV), subcutaneous (SC)] ascending doses in healthy volunteers or multiple SC ascending doses in subjects with rheumatoid arthritis (RA).

Methods ABT-122 pharmacokinetics was evaluated in three Phase 1 studies for up to 92 days. In Study 1, single- ascending IV (0.1, 0.3, 1, 3 and 10 mg/kg) and SC (0.3, 1 and 3 mg/kg) doses were evaluated in healthy volunteers. In Studies 2 and 3, multiple ascending SC doses (1 mg/kg biweekly, 0.5 to 3 mg/kg weekly for 8 weeks) were evaluated in subjects with RA on stable methotrexate (MTX) therapy. ABT-122 pharmacokinetic parameters were estimated using non-compartmental analyses.

Results Pharmacokinetic data were available from 48 healthy and 31 RA subjects with median body weights of 78 (range; 52 – 98) and 79 (range; 47 – 111) kg, respectively. ABT-122 pharmacokinetic profile showed multi-exponential disposition with more than dose-proportional exposure at the lower doses (0.1 – 1 mg/kg) and approximately dose-proportional exposure at doses >1 mg/kg. With SC dosing, ABT-122 absolute bioavailability was approximately 50% and maximum serum concentrations were reached 3 – 4 days after dosing. After the last dose, ABT-122 AUC accumulation ratio was 3.8 to 5.6 with steady-state appearing to be achieved by 5 weeks of SC dosing. ABT-122 Cmax to Ctrough ratio was 2.6 and 1.3 for biweekly and weekly dosing, respectively (corresponding effective half-life of 10 days with biweekly dosing and 18 days with weekly dosing). In most of the subjects, anti-drug antibodies detected had no detectable impact on pharmacokinetics, safety or tolerability profile of ABT-122.

Conclusions ABT-122 is characterized by a pharmacokinetic profile favorable for biweekly subcutaneous administration. The results from these three phase 1 studies supported advancing ABT-122 to Phase 2 testing in subjects with rheumatoid and psoriatic arthritis.

Disclosure of Interest G. Ahmed Shareholder of: AbbVie, Employee of: AbbVie, S. Goss Shareholder of: AbbVie, Employee of: AbbVie, P. Jiang Shareholder of: AbbVie, Employee of: AbbVie, H. Mansikka Shareholder of: AbbVie, Employee of: AbbVie, R. Padley Shareholder of: AbbVie, Employee of: AbbVie, A. Othman Shareholder of: AbbVie, Employee of: AbbVie

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.