Cargando…

Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)

Neublastin (BG00010) is a first-in-class, glial cell–derived neurotrophic factor shown in preclinical studies and an early clinical trial to have potential for the treatment of neuropathic pain. SPRINT was a phase 2, multicenter, double-blinded, placebo-controlled study to evaluate efficacy/safety o...

Descripción completa

Detalles Bibliográficos
Autores principales: Backonja, Miroslav, Williams, Leslie, Miao, Xiaopeng, Katz, Nathaniel, Chen, Crystal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761750/
https://www.ncbi.nlm.nih.gov/pubmed/28746076
http://dx.doi.org/10.1097/j.pain.0000000000000983
_version_ 1783291594485530624
author Backonja, Miroslav
Williams, Leslie
Miao, Xiaopeng
Katz, Nathaniel
Chen, Crystal
author_facet Backonja, Miroslav
Williams, Leslie
Miao, Xiaopeng
Katz, Nathaniel
Chen, Crystal
author_sort Backonja, Miroslav
collection PubMed
description Neublastin (BG00010) is a first-in-class, glial cell–derived neurotrophic factor shown in preclinical studies and an early clinical trial to have potential for the treatment of neuropathic pain. SPRINT was a phase 2, multicenter, double-blinded, placebo-controlled study to evaluate efficacy/safety of 5 neublastin doses (50, 150, 400, 800, and 1200 μg/kg) administered as an intravenous injection 3 times/week for 1 week in patients with chronic painful lumbosacral radiculopathy, utilizing Bayesian response-adaptive study design. Primary endpoint was change from baseline in mean 24-hour average general pain intensity over a 5-day period (week 1) after the last dose, analyzed using a Bayesian normal dynamic linear model. One hundred seventy-six patients were randomized and received treatment (placebo n = 48, 50 μg/kg n = 38, 150 μg/kg n = 13, 400 μg/kg n = 16, 800 μg/kg n = 20, 1200 μg/kg n = 41). Among the tested neublastin doses, the lowest dose (50 μg/kg) showed the greatest difference from placebo for change from baseline in mean average general pain intensity at week 1 after last dose, followed by the highest dose (1200 μg/kg) (posterior mean difference −1.36 [95% credible interval −2.22 to −0.52] and −0.75 [−1.59 to 0.08], respectively). Similar trends were observed in secondary efficacy endpoints. The most common adverse event in all neublastin dose groups was pruritus (79% vs 10% with placebo). There was no dose–response relationship with respect to primary/secondary efficacy outcomes or incidence of pruritus, despite dose-proportional increases in serum neublastin concentrations. In conclusion, while this study showed some evidence of pain relief with neublastin, particularly at the lowest dose, there was no clear dose–response relationship for pain reduction or the most common adverse event of pruritus.
format Online
Article
Text
id pubmed-5761750
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Wolters Kluwer
record_format MEDLINE/PubMed
spelling pubmed-57617502018-01-31 Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial) Backonja, Miroslav Williams, Leslie Miao, Xiaopeng Katz, Nathaniel Chen, Crystal Pain Research Paper Neublastin (BG00010) is a first-in-class, glial cell–derived neurotrophic factor shown in preclinical studies and an early clinical trial to have potential for the treatment of neuropathic pain. SPRINT was a phase 2, multicenter, double-blinded, placebo-controlled study to evaluate efficacy/safety of 5 neublastin doses (50, 150, 400, 800, and 1200 μg/kg) administered as an intravenous injection 3 times/week for 1 week in patients with chronic painful lumbosacral radiculopathy, utilizing Bayesian response-adaptive study design. Primary endpoint was change from baseline in mean 24-hour average general pain intensity over a 5-day period (week 1) after the last dose, analyzed using a Bayesian normal dynamic linear model. One hundred seventy-six patients were randomized and received treatment (placebo n = 48, 50 μg/kg n = 38, 150 μg/kg n = 13, 400 μg/kg n = 16, 800 μg/kg n = 20, 1200 μg/kg n = 41). Among the tested neublastin doses, the lowest dose (50 μg/kg) showed the greatest difference from placebo for change from baseline in mean average general pain intensity at week 1 after last dose, followed by the highest dose (1200 μg/kg) (posterior mean difference −1.36 [95% credible interval −2.22 to −0.52] and −0.75 [−1.59 to 0.08], respectively). Similar trends were observed in secondary efficacy endpoints. The most common adverse event in all neublastin dose groups was pruritus (79% vs 10% with placebo). There was no dose–response relationship with respect to primary/secondary efficacy outcomes or incidence of pruritus, despite dose-proportional increases in serum neublastin concentrations. In conclusion, while this study showed some evidence of pain relief with neublastin, particularly at the lowest dose, there was no clear dose–response relationship for pain reduction or the most common adverse event of pruritus. Wolters Kluwer 2017-09 2017-08-23 /pmc/articles/PMC5761750/ /pubmed/28746076 http://dx.doi.org/10.1097/j.pain.0000000000000983 Text en Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Research Paper
Backonja, Miroslav
Williams, Leslie
Miao, Xiaopeng
Katz, Nathaniel
Chen, Crystal
Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)
title Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)
title_full Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)
title_fullStr Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)
title_full_unstemmed Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)
title_short Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)
title_sort safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using bayesian adaptive design (the sprint trial)
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761750/
https://www.ncbi.nlm.nih.gov/pubmed/28746076
http://dx.doi.org/10.1097/j.pain.0000000000000983
work_keys_str_mv AT backonjamiroslav safetyandefficacyofneublastininpainfullumbosacralradiculopathyarandomizeddoubleblindedplacebocontrolledphase2trialusingbayesianadaptivedesignthesprinttrial
AT williamsleslie safetyandefficacyofneublastininpainfullumbosacralradiculopathyarandomizeddoubleblindedplacebocontrolledphase2trialusingbayesianadaptivedesignthesprinttrial
AT miaoxiaopeng safetyandefficacyofneublastininpainfullumbosacralradiculopathyarandomizeddoubleblindedplacebocontrolledphase2trialusingbayesianadaptivedesignthesprinttrial
AT katznathaniel safetyandefficacyofneublastininpainfullumbosacralradiculopathyarandomizeddoubleblindedplacebocontrolledphase2trialusingbayesianadaptivedesignthesprinttrial
AT chencrystal safetyandefficacyofneublastininpainfullumbosacralradiculopathyarandomizeddoubleblindedplacebocontrolledphase2trialusingbayesianadaptivedesignthesprinttrial