دورية أكاديمية
أعرض في EDS

First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti-IL-20 Monoclonal Antibody in Patients with Psoriasis.

التفاصيل البيبلوغرافية
العنوان: First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti-IL-20 Monoclonal Antibody in Patients with Psoriasis.
المؤلفون: Gottlieb AB; Department of Dermatology, Tufts Medical Center, Boston, MA, United States of America; Department of Dermatology, Tufts University School of Medicine, Boston, MA, United States of America., Krueger JG; The Rockefeller University, New York, NY, United States of America., Sandberg Lundblad M; Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark., Göthberg M; Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark., Skolnick BE; Medical-Science, Inflammation, Novo Nordisk Inc., Princeton, NJ, United States of America.
المصدر: PloS one [PLoS One] 2015 Aug 07; Vol. 10 (8), pp. e0134703. Date of Electronic Publication: 2015 Aug 07 (Print Publication: 2015).
نوع المنشور: Clinical Trial, Phase I; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Antibodies, Monoclonal/*therapeutic use , Antibodies, Neutralizing/*therapeutic use , Interleukins/*immunology , Psoriasis/*drug therapy, Adult ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing/adverse effects ; Antibodies, Neutralizing/pharmacology ; Broadly Neutralizing Antibodies ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Middle Aged ; Psoriasis/pathology ; Recombinant Proteins/adverse effects ; Recombinant Proteins/pharmacokinetics ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use ; Treatment Outcome ; Young Adult
مستخلص: Background: The current trial was a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the recombinant monoclonal anti-interleukin-20 (IL-20) antibody, NNC0109-0012, which targets the inflammatory cytokine IL-20.
Methods: In total, 48 patients aged 18 to 75 years with moderate to severe stable chronic plaque psoriasis with affected body surface area ≥15% and physician global assessment score ≥3 were enrolled in this randomized, double-blind, multicenter, placebo-controlled, phase 1 dose-escalation trial. Patients were randomized within each single dose cohort (0.01, 0.05, 0.2, 0.6, 1.5, or 3.0 mg/kg) or multiple dose cohort (0.05, 0.2, 0.5, 1.0, or 2.0 mg/kg; 1 dose every other week for 7 weeks) of NNC0109-0012 or placebo in a 3:1 ratio. In the expansion phase, 7 patients were randomized to weekly doses of 2.0 mg/kg NNC0109-0012 or placebo for 7 weeks. The primary objective, safety and tolerability, was assessed by evaluating adverse events (AEs). Additional endpoints included pharmacokinetics, pharmacodynamics, and clinical response (assessed using the Psoriasis Area and Severity Index [PASI] score).
Results: AEs were reported in 85% of patients (n = 40) in the initial study phases (NNC0109-0012, 83%; placebo, 92%) and in 4 of 7 patients in the multiple-dose expansion phase. One serious AE was reported but was judged not to be causally related to NNC0109-0012. No dose-limiting toxicities were reported. NNC0109-0012 pharmacokinetics was similar to other monoclonal antibodies, with an average half-life of approximately 3 weeks. There was a dose-proportional increase in area under the curve and maximum concentration after single dosing. No substantial changes in pharmacodynamic parameters were observed. The expansion phase was terminated early due to apparent lack of PASI improvement.
Conclusion: Single and multiple doses of NNC0109-0012, ranging from 0.05 to 3.0 mg/kg, were well tolerated in patients with psoriasis and exhibited pharmacokinetics similar to that of other monoclonal antibodies.
Trial Registration: ClinicalTrials.gov NCT01261767.
References: Adv Ther. 2015 Mar;32(3):228-38. (PMID: 25749867)
Cell. 2001 Jan 12;104(1):9-19. (PMID: 11163236)
J Immunol. 2001 Oct 1;167(7):3545-9. (PMID: 11564763)
Trends Immunol. 2002 Jan;23(1):47-53. (PMID: 11801454)
J Immunol. 2002 Jun 1;168(11):5397-402. (PMID: 12023331)
Lancet. 2003 Apr 5;361(9364):1197-204. (PMID: 12686053)
J Invest Dermatol. 2003 Dec;121(6):1306-11. (PMID: 14675174)
J Investig Dermatol Symp Proc. 2004 Mar;9(2):136-9. (PMID: 15083780)
J Am Acad Dermatol. 2005 Jan;52(1):23-6. (PMID: 15627076)
Nat Rev Drug Discov. 2005 Jan;4(1):19-34. (PMID: 15688070)
Clin Immunol. 2005 Oct;117(1):65-72. (PMID: 16043414)
Br J Dermatol. 2005 Nov;153(5):911-8. (PMID: 16225599)
Curr Med Res Opin. 2006 May;22(5):989-1000. (PMID: 16709321)
Exp Dermatol. 2006 Dec;15(12):991-1004. (PMID: 17083366)
J Immunol. 2007 Feb 15;178(4):2229-40. (PMID: 17277128)
Arch Intern Med. 2007 Aug 13-27;167(15):1670-5. (PMID: 17698691)
J Leukoc Biol. 2008 May;83(5):1181-93. (PMID: 18281438)
J Am Acad Dermatol. 2009 Feb;60(2):218-24. (PMID: 19022533)
Br J Dermatol. 2009 Feb;160(2):284-96. (PMID: 18945296)
J Am Acad Dermatol. 2009 Mar;60(3):394-401. (PMID: 19231638)
J Mol Med (Berl). 2009 May;87(5):523-36. (PMID: 19330474)
Eur J Immunol. 2009 Oct;39(10):2779-88. (PMID: 19731362)
J Eur Acad Dermatol Venereol. 2010 Apr;24 Suppl 2:10-6. (PMID: 20443995)
Recent Pat Inflamm Allergy Drug Discov. 2012 Jan;6(1):3-21. (PMID: 22022925)
J Am Acad Dermatol. 2012 Mar;66(3):369-75. (PMID: 22041254)
Clin Immunol. 2012 May;143(2):116-27. (PMID: 22459704)
Br J Dermatol. 2012 Jul;167(1):92-102. (PMID: 22458549)
Br J Dermatol. 2012 Nov;167 Suppl 3:12-20. (PMID: 23082811)
J Invest Dermatol. 2014 Feb;134(2):389-95. (PMID: 23892591)
سلسلة جزيئية: ClinicalTrials.gov NCT01261767
المشرفين على المادة: 0 (Antibodies, Monoclonal)
0 (Antibodies, Monoclonal, Humanized)
0 (Antibodies, Neutralizing)
0 (Broadly Neutralizing Antibodies)
0 (Interleukins)
0 (Recombinant Proteins)
82WG3POL9W (Fletikumab)
U91R7IMG8U (interleukin 20)
تواريخ الأحداث: Date Created: 20150808 Date Completed: 20160509 Latest Revision: 20191210
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4529098
DOI: 10.1371/journal.pone.0134703
PMID: 26252485
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0134703