Novel Orally Administered Recombinant Anti-TNF Alpha Fusion Protein for the Treatment of Ulcerative Colitis: Results From a Phase 2a Clinical Trial.
Journal
Journal of clinical gastroenterology
ISSN: 1539-2031
Titre abrégé: J Clin Gastroenterol
Pays: United States
ID NLM: 7910017
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
received:
13
05
2019
accepted:
23
12
2019
pubmed:
6
6
2020
medline:
9
7
2021
entrez:
6
6
2020
Statut:
ppublish
Résumé
OPRX-106 is an orally administered BY2 plant cell-expressing recombinant TNF fusion protein (TNFR). Oral administration of OPRX-106 was shown to be safe and effective in inducing favorable anti-inflammatory immune modulation in humans. The current study was aimed at determining the safety and efficacy of OPRX-106 in patients with ulcerative colitis (UC). Twenty-five patients with active mild-to-moderate UC were enrolled in an open-label trial. Patients were randomized to receive 2 or 8 mg of OPRX-106 administered orally once daily, for 8 weeks. Patients were monitored for safety and efficacy including clinical response or clinical remission, based on the Mayo score. The histopathological improvement in Geboes score, calprotectin level and hs-CRP, and exploratory immune parameters by means of fluorescence-activated cell sorting and cytokine levels were monitored. Oral administration of OPRX-106 was found to be safe and well tolerated without absorption into the circulation. Out of 24 patients, 18 completed the trial. The analysis of the patients completing treatment demonstrated clinical efficacy as measured by clinical response or remission in 67% and 28%, respectively. Reduction in calprotectin levels and improved Geboes score were noted in the majority of the treated patients. The beneficial clinical effect was associated with an increase in a CD4+CD25+FoxP3 subset of suppressor lymphocytes and a reduction in interleukin 6 and interferon gamma serum levels. Oral administration of the nonabsorbable OPRX-106 is safe and effective in mild-to-moderate UC, and not associated with immune suppression, while inducing favorable anti-inflammatory immune modulation.
Sections du résumé
BACKGROUND AND OBJECTIVE
OPRX-106 is an orally administered BY2 plant cell-expressing recombinant TNF fusion protein (TNFR). Oral administration of OPRX-106 was shown to be safe and effective in inducing favorable anti-inflammatory immune modulation in humans. The current study was aimed at determining the safety and efficacy of OPRX-106 in patients with ulcerative colitis (UC).
METHODS
Twenty-five patients with active mild-to-moderate UC were enrolled in an open-label trial. Patients were randomized to receive 2 or 8 mg of OPRX-106 administered orally once daily, for 8 weeks. Patients were monitored for safety and efficacy including clinical response or clinical remission, based on the Mayo score. The histopathological improvement in Geboes score, calprotectin level and hs-CRP, and exploratory immune parameters by means of fluorescence-activated cell sorting and cytokine levels were monitored.
RESULTS
Oral administration of OPRX-106 was found to be safe and well tolerated without absorption into the circulation. Out of 24 patients, 18 completed the trial. The analysis of the patients completing treatment demonstrated clinical efficacy as measured by clinical response or remission in 67% and 28%, respectively. Reduction in calprotectin levels and improved Geboes score were noted in the majority of the treated patients. The beneficial clinical effect was associated with an increase in a CD4+CD25+FoxP3 subset of suppressor lymphocytes and a reduction in interleukin 6 and interferon gamma serum levels.
CONCLUSIONS
Oral administration of the nonabsorbable OPRX-106 is safe and effective in mild-to-moderate UC, and not associated with immune suppression, while inducing favorable anti-inflammatory immune modulation.
Identifiants
pubmed: 32501868
pii: 00004836-202102000-00008
doi: 10.1097/MCG.0000000000001314
pmc: PMC7803480
doi:
Substances chimiques
Leukocyte L1 Antigen Complex
0
Recombinant Fusion Proteins
0
Tumor Necrosis Factor Inhibitors
0
Tumor Necrosis Factor-alpha
0
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
134-140Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.
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