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First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti–IL-20 Monoclonal Antibody in Patients with Psoriasis
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529098/ https://www.ncbi.nlm.nih.gov/pubmed/26252485 http://dx.doi.org/10.1371/journal.pone.0134703 |
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author | Gottlieb, Alice B. Krueger, James G. Sandberg Lundblad, Mia Göthberg, Marie Skolnick, Brett E. |
author_facet | Gottlieb, Alice B. Krueger, James G. Sandberg Lundblad, Mia Göthberg, Marie Skolnick, Brett E. |
author_sort | Gottlieb, Alice B. |
collection | PubMed |
description | 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 |
format | Online Article Text |
id | pubmed-4529098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45290982015-08-12 First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti–IL-20 Monoclonal Antibody in Patients with Psoriasis Gottlieb, Alice B. Krueger, James G. Sandberg Lundblad, Mia Göthberg, Marie Skolnick, Brett E. PLoS One Research Article 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 Public Library of Science 2015-08-07 /pmc/articles/PMC4529098/ /pubmed/26252485 http://dx.doi.org/10.1371/journal.pone.0134703 Text en © 2015 Gottlieb et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gottlieb, Alice B. Krueger, James G. Sandberg Lundblad, Mia Göthberg, Marie Skolnick, Brett E. First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti–IL-20 Monoclonal Antibody in Patients with Psoriasis |
title | First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti–IL-20 Monoclonal Antibody in Patients with Psoriasis |
title_full | First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti–IL-20 Monoclonal Antibody in Patients with Psoriasis |
title_fullStr | First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti–IL-20 Monoclonal Antibody in Patients with Psoriasis |
title_full_unstemmed | First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti–IL-20 Monoclonal Antibody in Patients with Psoriasis |
title_short | First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti–IL-20 Monoclonal Antibody in Patients with Psoriasis |
title_sort | first-in-human, phase 1, randomized, dose-escalation trial with recombinant anti–il-20 monoclonal antibody in patients with psoriasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529098/ https://www.ncbi.nlm.nih.gov/pubmed/26252485 http://dx.doi.org/10.1371/journal.pone.0134703 |
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