Population Pharmacokinetics of the TNF-α and IL-17A Dual-Variable Domain Antibody ABT-122 in Healthy Volunteers and Subjects With Psoriatic or Rheumatoid Arthritis: Analysis of Phase 1 and 2 Clinical Trials

Journal of Clinical Pharmacology

Volumn 58, Issue 6, 2018, Pages 803-813

  Khatri, Amit ^a   Othman, Ahmed A ^a  

^a ABBVIE INC   (United States)

Author keywords

ABT 122; IL 17; pharmacokinetics; psoriatic arthritis; rheumatoid arthritis; TNF

Indexed keywords

C REACTIVE PROTEIN; INTERLEUKIN 17; METHOTREXATE; REMTOLUMAB; SERUM ALBUMIN; TUMOR NECROSIS FACTOR; ABT-122; ANTIRHEUMATIC AGENT; IMMUNOGLOBULIN;

ABSORPTION RATE CONSTANT; ADULT; AREA UNDER THE CURVE; ARTICLE; BODY WEIGHT; BOOTSTRAPPING; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFICACY; DRUG FORMULATION; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; PHARMACOKINETIC PARAMETERS; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PSORIATIC ARTHRITIS; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; VOLUME OF DISTRIBUTION; VOLUME OF DISTRIBUTION AT STEADY-STATE; BIOAVAILABILITY; CLINICAL TRIAL; METABOLIC CLEARANCE RATE; MIDDLE AGED; NORMAL HUMAN; RANDOMIZATION; YOUNG ADULT;

ADULT; ANTIRHEUMATIC AGENTS; ARTHRITIS, PSORIATIC; ARTHRITIS, RHEUMATOID; BIOLOGICAL AVAILABILITY; BODY WEIGHT; DOUBLE-BLIND METHOD; FEMALE; HEALTHY VOLUNTEERS; HUMANS; IMMUNOGLOBULINS; INTERLEUKIN-17; MALE; METABOLIC CLEARANCE RATE; METHOTREXATE; MIDDLE AGED; RANDOM ALLOCATION; TUMOR NECROSIS FACTOR-ALPHA; YOUNG ADULT;

EID: 85041035977     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1002/jcph.1068     Document Type: Article

References (35)

1. Frleta M, Siebert S, McInnes IB. The interleukin-17 pathway in psoriasis and psoriatic arthritis: disease pathogenesis and possibilities of treatment. Curr Rheumatol Rep. 2014;16(4):414.
2. Enbrel [package insert]. Thousand Oaks, CA: Immunex Corporation; 2015.
3. Remicade [package insert]. Malvern, PA: Centocor Ortho Biotech Inc.; 2015.
4. Humira [package insert]. North Chicago, IL: AbbVie Inc.; 2016.
5. Genovese MC, Greenwald M, Cho CS, et al. A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2014;66(7):1693–1704.
6. Genovese MC, Durez P, Richards HB, et al. Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding double-blind, randomised, placebo controlled study. Ann Rheum Dis. 2013;72(6):863–869.
7. Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2016.
8. Siliq [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals; 2017.
9. Cosentyx [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016.
10. Mease PJ, Genovese MC, Greenwald MW, et al. Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med. 2014;370(24):2295–2306.
11. Nam JL, Ramiro S, Gaujoux-Viala C, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2014;73:516–528.
12. Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11(10):763–776.
13. Koenders MI, Marijnissen RJ, Devesa I, et al. Tumor necrosis factor-interleukin-17 interplay induces S100A8, interleukin-1beta, and matrix metalloproteinases, and drives irreversible cartilage destruction in murine arthritis: rationale for combination treatment during arthritis. Arthritis Rheum. 2011;63:2329–2339.
14. van Hamburg JP, Asmawidjaja PS, Davelaar N, et al. Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum. 2011;63(1):73–83.
15. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):244–279.
16. Mease PJ, Genovese MC, Weinblatt M, et al. Safety and efficacy of ABT-122, a TNF and IL-17-targeted dual variable domain (DVD)-Ig™, in psoriatic arthritis patients with inadequate response to methotrexate: Results from a phase 2 trial. Arthritis Rheum. 2016;68:1268–1270.
17. Genovese MC, Weinblatt M, Aelion JA, et al. ABT-122, a TNF- and IL-17-targeted dual variable domain (DVD)-ig™ in rheumatoid arthritis patients with inadequate response to methotrexate: Results from a phase 2 trial. Arthritis Rheumatol. 2016;68:855–857.
18. Khatri A, Goss S, Jiang P, Mansikka H, Othman AA. Pharmacokinetics of ABT-122, a TNF-α- and IL-17A-targeted dual-variable domain immunoglobulin, in healthy subjects and patients with rheumatoid arthritis: results from three phase I trials [published online ahead of print 2017]. Clin Pharmacokinet. https://doi.org/10.1007/s40262-017-0580-y
19. Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84(5):548–558.
20. Fleischmann RM, Wagner F, Kivitz AJ, et al. Safety, tolerability, and pharmacodynamics of ABT-122, a TNF- and IL-17–targeted dual variable domain (DVD)-Ig™ in patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75(2):498.
21. Mansikka H, Ruzek M, Hugunin M, et al. Safety, tolerability, and functional activity of ABT-122, a dual TNF and IL-17a-targeted DVD-ig™, following single-dose administration in healthy subjects. Arthritis Rheum. 2014;66(S10):422–423.
22. Genovese MC, Weinblatt M, Aelion JA, et al. ABT-122, a TNF and IL-17–targeted dual variable domain (DVD)–Ig™ in rheumatoid arthritis patients with inadequate response to methotrexate: results from a phase 2 trial. Arthritis Rheum. 2016;68(S10):855–857.
23. Mease PJ, Genovese MC, Weinblatt M, et al. Safety and efficacy of ABT-122, a TNF and IL-17–targeted dual variable domain (DVD)–Ig™, in psoriatic arthritis patients with inadequate response to methotrexate: results from a phase 2 trial. Arthritis Rheum. 2016;68(S10):1268–1270.
24. Dirks NL, Meibohm B. Population pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49(10):633–659.
25. Hsieh C-M, Cuff C, Tarcsa E, Hugunin M. FRI0303 Discovery and characterization of ABT-122, an anti-TNF/IL-17 DVD-IG™ molecule as a potential therapeutic candidate for rheumatoid arthritis [abstract]. Ann Rheum Dis. 2014;73(suppl 2):495.
26. Kaymakcalan Z, Sakorafas P, Bose S, et al. Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, and etanercept in binding to soluble and membrane tumor necrosis factor. Clin Immunol. 2009;131(2):308–316.
27. Liu L, Lu J, Allan BW, et al. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. J Inflamm Res. 2016;9:39–50.
28. Xu ZH, Lee H, Vu T, et al. Population pharmacokinetics of golimumab in patients with ankylosing spondylitis: impact of body weight and immunogenicity. Int J Clin Pharmacol Ther. 2010;48(9):596–607.
29. Gomez-Mantilla JD, Troconiz IF, Parra-Guillen Z, Garrido MJ. Review on modeling anti-antibody responses to monoclonal antibodies. J Pharmacokinet Pharmacodyn. 2014;41:523–536.
30. Zhu Y, Hu C, Lu M, et al. Population pharmacokinetic modeling of ustekinumab, a human monoclonal antibody targeting IL-12/23p40, in patients with moderate to severe plaque psoriasis. J Clin Pharmacol. 2009;49:162–175.
31. Zhou L, Hoofring SA, Wu Y, et al. Stratification of antibody-positive subjects by antibody level reveals an impact of immunogenicity on pharmacokinetics. AAPS J. 2013;15:30–40.
32. Nader A, Beck D, Noertersheuser P, Williams D, Mostafa N. Population pharmacokinetics and immunogenicity of adalimumab in adult patients with moderate-to-severe hidradenitis suppurativa. Clin Pharmacokinet. 2017;56(9):1091–1102.
33. CDER. Application NumberClinical Pharmacology and Biopharmaceutics Review of Ixekizumab. FDA, 25521Orig1s000. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/125521Orig1s000ClinPharmR.pdf
34. Murdaca G, Spanò F, Contatore M, et al. Immunogenicity of infliximab and adalimumab: what is its role in hypersensitivity and modulation of therapeutic efficacy and safety? Expert Opin Drug Saf. 2016;15:43–52.
35. Vultaggio A, Nencini F, Pratesi S, et al. Manifestations of antidrug antibodies response: hypersensitivity and infusion reactions. J Interferon Cytokine Res. 2014;34:946–952.