Safety, PK, and PD of recombinant anti-interleukin-21 monoclonal antibody in a first-in-human trial

International Journal of Clinical Pharmacology and Therapeutics

Volumn 54, Issue 4, 2016, Pages 243-252

  Ignatenko, Stanislav ^a   Skrumsager, Birte K ^b   Mouritzen, Ulrik ^b  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b NOVO NORDISK A S   (Denmark)

Author keywords

Dose escalation trial; First in human trial; Interleukin 21 monoclonal antibody; Rheumatoid arthritis

Indexed keywords

DRUG ANTIBODY; INTERLEUKIN 21; METHOTREXATE; MONOCLONAL ANTIBODY; NNC 0114 0005; PLACEBO; UNCLASSIFIED DRUG; INTERLEUKIN DERIVATIVE; RECOMBINANT PROTEIN;

ADULT; ANTIGEN ANTIBODY COMPLEX; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; ECZEMA; GASTROINTESTINAL DISEASE; HEADACHE; HUMAN; INFECTION; INFESTATION; INFUSION RELATED REACTION; INJECTION SITE REACTION; INJURY; INTOXICATION; MALE; MAXIMUM PLASMA CONCENTRATION; NEUROLOGIC DISEASE; PHARMACODYNAMICS; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; RHINITIS; RHINOPHARYNGITIS; TIME TO MAXIMUM PLASMA CONCENTRATION; ARTHRITIS, RHEUMATOID; CLINICAL TRIAL; IMMUNOLOGY; MIDDLE AGED; PHASE 1 CLINICAL TRIAL;

ADULT; ANTIBODIES, MONOCLONAL; ARTHRITIS, RHEUMATOID; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HUMANS; INTERLEUKINS; MALE; MIDDLE AGED; RECOMBINANT PROTEINS;

EID: 84964556828     PISSN: 09461965     EISSN: None     Source Type: Journal    
DOI: 10.5414/CP202474     Document Type: Article

References (31)

1. Bathon JM, Fleischmann RM, Van der Heijde D, Tesser JR, Peloso PM, Chon Y, White B. Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid arthritis. J Rheumatol. 2006; 33: 234-243.
2. Breedveld FC, Weisman MH, Kavanaugh A F, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006; 54: 26-37.
3. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Martín Mola E, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M; TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004; 363: 675-681.
4. Moreland L. Unmet needs in rheumatoid arthritis. Arthritis Res Ther. 2005; 7 (Suppl. 3): S2-S8.
5. Schipper LG, Vermeer M, Kuper HH, Hoekstra MO, Haagsma CJ, Den Broeder AA, van Riel P, Fransen J, van de Laar MA. A tight control treatment strategy aiming for remission in early rheumatoid arthritis is more effective than usual care treatment in daily clinical practice: a study of two cohorts in the Dutch Rheumatoid Arthritis Monitoring registry. Ann Rheum Dis. 2012; 71: 845-850.
6. Siddiqui MA The efficacy and tolerability of newer biologics in rheumatoid arthritis: best current evidence. Curr Opin Rheumatol. 2007; 19: 308-313.
7. Brandt K, Singh PB, Bulfone-Paus S, Rückert R. Interleukin-21: a new modulator of immunity, infection, and cancer. Cytokine Growth Factor Rev. 2007; 18: 223-232.
8. Davis ID, Skak K, Smyth MJ, Kristjansen PE, Miller DM, Sivakumar PV. Interleukin-21 signaling: functions in cancer and autoimmunity. Clin Cancer Res. 2007; 13: 6926-6932.
9. Ettinger R, Kuchen S, Lipsky PE. Interleukin 21 as a target of intervention in autoimmune disease. Ann Rheum Dis. 2008; 67 (Suppl. 3): iii83-iii86.
10. Spolski R, Leonard WJ. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol. 2008; 26: 57-79.
11. Li J, Shen W, Kong K, Liu Z. Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion in rheumatoid arthritis. Scand J Immunol. 2006; 64: 515-522.
12. Rasmussen TK, Andersen T, Hvid M, Hetland ML, Hørslev-Petersen K, Stengaard-Pedersen K, Holm CK, Deleuran B. Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease activity and with radiographic status in patients with early rheumatoid arthritis. J Rheumatol. 2010; 37: 2014-2020.
13. Liu R, Wu Q, Su D, Che N, Chen H, Geng L, Chen J, Chen W, Li X, Sun L. A regulatory effect of IL-21 on T follicular helper-like cell and B cell in rheumatoid arthritis. Arthritis Res Ther. 2012; 14: R255.
14. Young DA, Hegen M, Ma HL, Whitters MJ, Albert LM, Lowe L, Senices M, Wu P W, Sibley B, Leathurby Y, Brown T P, Nickerson-Nutter C, Keith JC Jr, Collins M. Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum. 2007; 56: 1152-1163.
15. Jang E, Cho SH, Park H, Paik DJ, Kim JM, Youn J. A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25-T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice. J Immunol. 2009; 182: 4649-4656.
16. Kwok SK, Cho ML, Park MK, Oh HJ, Park JS, Her YM, Lee S Y, Youn J, Ju JH, Park KS, Kim SI, Kim H Y, Park SH. Interleukin-21 promotes osteo-clastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis. Arthritis Rheum. 2012; 64: 740-751.
17. Maurer M F, Garrigues U, Jaspers SR, Meengs B, Rixon M W, Stevens BL, Lewis KB, Julien SH, Bukowski TR, Wolf AC, Hamacher NB, Snavely M, Dillon SR. Generation and characterization of human anti-human IL-21 neutralizing monoclonal antibodies. MAbs. 2012; 4: 69-83.
18. Sondermann P, Huber R, Oosthuizen V, Jacob U. The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex. Nature. 2000; 406: 267-273.
19. Tao MH, Smith RI, Morrison SL. Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation. J Exp Med. 1993; 178: 661-667.
20. Canfield SM, Morrison SL. The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region. J Exp Med. 1991; 173: 1483-1491.
21. World Medical Association. 2004. Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Available at: http://www.wma.net/en/30publications/10policies/b3/. Accessed July 2, 2015.
22. International Conference on Harmonisation. ICH Harmonised Tripartite Guideline. Good Clinical Practice. 01 May 1996.
23. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries J F, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31: 315-324.
24. Shankar G, Devanarayan V, Amaravadi L, Barrett YC, Bowsher R, Finco-Kent D, Fiscella M, Gorovits B, Kirschner S, Moxness M, Parish T, Quarmby V, Smith H, Smith W, Zuckerman LA, Koren E. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. J Pharm Biomed Anal. 2008; 48: 1267-1281.
25. van Gestel AM, Haagsma CJ, van Riel PL Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998; 41: 1845-1850.
26. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, Katz LM, Lightfoot R Jr Paulus H, Strand V, Tugwell P, Weinblatt M, James Williams H, Wolfe F, Kieszak S. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995; 38: 727-735.
27. Leirisalo-Repo M. What is the best treatment strategy for early RA? Best Pract Res Clin Rheumatol. 2013; 27: 523-536.
28. Weyand CM, Klimiuk PA, Goronzy JJ. Heterogeneity of rheumatoid arthritis: from phenotypes to genotypes. Springer Semin Immunopathol. 1998; 20: 5-22.
29. Yuan FL, Hu W, Lu WG, Li X, Li J P, Xu RS, Li C W, Chen FH, Jin C. Targeting interleukin-21 in rheumatoid arthritis. Mol Biol Rep. 2011; 38: 1717-1721.
30. Lachmann HJ, Lowe P, Felix SD, Rordorf C, Leslie K, Madhoo S, Wittkowski H, Bek S, Hartmann N, Bosset S, Hawkins PN, Jung T. In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromes. J Exp Med. 2009; 206: 1029-1036.
31. Niu X, He D, Zhang X, Yue T, Li N, Zhang JZ, Dong C, Chen G. IL-21 regulates Th17 cells in rheumatoid arthritis. Hum Immunol. 2010; 71: 334-341.