Clinical trials

Completed Trials

Traumatic Brain Injury (TBI)

So far, five clinical studies have been conducted with the test substance Ronopterin (INN)*.

Phase 1a (2006 – 2007) First in Human – Dose finding trial / 31 volunteers
Phase 1b (2008) Repeated dosing / 16 volunteers
Phase 2a (2009 – 2012) NOSTRA trial to evaluate safety, tolerability, pharmacodynamics and pharmacokinetics in patients with moderate and severe TBI / 31 patients
Phase 1c (2016 – 2016) Evaluation on renal perfusion / 16 volunteers
Phase 3a (2016 – 2020) Double blind, randomized, placebo-controlled NOSTRA III trial to asses safety and efficacy in patients with moderate and severe TBI / 224 patients

NOSTRA III main post-hoc analysis outcome

Significantly reduced brain microdialysate glutamate levels
Reduced therapy aggressiveness
Improved neurological outcome (extended Glasgow Outcome)
Improved Quality of Life (QOLIBRI)
No safety concerns throughout the trial (unblinded DMC)

*International Nonproprietary Name

Next Trials

Core Indication

Traumatic Brain Injury (TBI)

Phase 2b (US) Dose ranging to reduce elevated brain glutamate for NDA (fast track)
Phase 3b (EU) High dose with adapted therapeutic window to improve neurological outcome for MAA

Additional Indications

Neuro-Oncology

Phase 1 (EU/US) Dose finding to reduce brain edema in Glioblastoma
Phase 1 (EU/US) Dose finding to reduce brain edema in brain metastases

Diabetic Retinopathy

Phase 1 (EU/US) Dose finding to reduce retinal edema

FIM= First In Man | NDA= New Drug Application | MAA= Market Authorization Application

Overview

Clinical Trials- completed and next trials

Corresponding literature

Tegtmeier F, Schinzel R, Beer R, Bulters D, LeFrant JY, Sahuquillo J, Unterberg A, Andrews P, Belli A, Ibanez J, Lagares A, Mokry M, Willschke H, Flüh C, Schmutzhard E; NOSTRA Investigators. Efficacy of Ronopterin (VAS203) in Patients with Moderate and Severe Traumatic Brain Injury (NOSTRA phase III trial): study protocol of a confirmatory, placebo-controlled, randomised, double blind, multi-centre study. Trials. 2020 Jan 14;21(1):80. doi: 10.1186/s13063-019-3965-4.
https://pubmed.ncbi.nlm.nih.gov/31937347/

Ott C, Bosch A, Winzer N, Friedrich S, Schinzel R, Tegtmeier F, Schmieder RE. Effects of the nitric oxide synthase inhibitor ronopterin (VAS203) on renal function in healthy volunteers. Br J Clin Pharmacol. 2019 Jan 21. doi:10.1111/bcp.13870.
https://www.ncbi.nlm.nih.gov/pubmed/30666700

Schinzel R. and Tegtmeier F; Chapter 8 - Nitric Oxide Synthase Inhibitors in Traumatic Brain Injury, In New Therapeutics for Traumatic Brain Injury, edited by Kim A. Heidenreich,, Academic Press, San Diego, 2017, Pages 133-144, ISBN 9780128026861,
http://dx.doi.org/10.1016/B978-0-12-802686-1.00008-0

Schwarzmaier SM, Terpolilli NA, Dienel A, Gallozzi M, Schinzel R, Tegtmeier F, Plesnila N. Endothelial nitric oxide synthase mediates arteriolar vasodilatation after traumatic brain injury in mice. J Neurotrauma. 2015 May 15;32(10):731-8. doi: 10.1089/neu.2014.3650.
https://www.ncbi.nlm.nih.gov/pubmed/25363688

Stover JF, Belli A, Boret H, Bulters D, Sahuquillo J, Schmutzhard E, Zavala E, Ungerstedt U, Schinzel R, Tegtmeier F; NOSTRA Investigators.. Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized Phase IIa trial (NOSTRA). J Neurotrauma. 2014 Oct 1;31(19):1599-606. doi: 10.1089/neu.2014.3344.
https://www.ncbi.nlm.nih.gov/pubmed/24831445

Terpolilli NA, Zweckberger K, Trabold R, Schilling L, Schinzel R, Tegtmeier F, Plesnila N. The novel nitric oxide synthase inhibitor 4-amino-tetrahydro-L-biopterine prevents brain edema formation and intracranial hypertension following traumatic brain injury in mice. J Neurotrauma. 2009 Nov;26(11):1963-75. doi: 10.1089/neu.2008-0853.
https://www.ncbi.nlm.nih.gov/pubmed/19514849