Clinical Trials

Date: 2017-09-21

Type of information: Results

phase: 2b

Announcement: update

Company: Neurovive Pharmaceutical (Sweden)

Product: NeuroSTAT® (cyclosporine)

Action mechanism:

• immunosuppressive agent. The active ingredient cyclosporine acts by preventing the death of mitochondria in damaged cells and the following cascade of intracellular biochemical events that lead to secondary tissue damage. By protecting a cell's mitochondria, NeuroVive's products ensure that energy production is preserved and a damaged cell's normal regenerative mechanisms can act to repair and maintain the cell.
• NeuroSTAT has received orphan drug designation status from both EMA and the FDA.

Disease: traumatic brain injury

Therapeutic area: Traumatology - CNS diseases

Country: Denmark

Trial details:

• The phase II CHIC (Copenhagen Head Injury Ciclosporin) study was an open label study. The primary objective with the study was to establish safety and to characterize the pharmacokinetic profile of two dosing regimens of NeuroSTAT in severe Traumatic Brain Injury (TBI) patients who require intensive care unit admission and monitoring of intracranial pressure via a ventricular catheter. 20 patients will be screened, and subsequently enrolled after clinical stabilisation. Thereafter, patients will receive 2.5 mg/kg bolus dose infusion of ciclosporin, followed by either 5 mg/kg/day or 10 mg/kg/day of ciclosporin as continuous infusion for 5 days+3 days monitoring at the intensive care unit. After an additional 30 days, a follow-up phone call will be made to the patient, or the patient's nursing staff, checking patient status and serious adverse events. The two dose levels will be investigated in 10 patients each, starting with the lower dose level for the first 10 patients. Patients will have samples of blood and cerebrospinal fluid drawn at pre-defined time points during the study for pharmacokinetic assessment and evaluation of biomarkers. Bedside monitoring with microdialysis and brain tissue oxygenation will be performed. The safety monitoring includes nephrotoxicity, hepatotoxicity, monitoring of intracranial pressure (ICP), infections monitoring and adverse events collection and reporting. (NCT01825044)

Latest news:

• • On September 21, 2017, NeuroVive Pharmaceutical announced positive feedback on its requested Scientific Advice (Protocol Assistance) from the European Medicinal agency (EMA), on the NeuroSTAT development plan for treatment of moderate to severe traumatic brain injury , including the design of its planned Phase IIb proof of concept study. Following results from the company’s clinical phase IIa CHIC (Copenhagen Head Injury Ciclosporin) study, conducted at Rigshospitalet in Copenhagen, Denmark, and the positive results from the preclinical studies, NeuroVive requested Scientific Advice with EMA on the continued clinical development program to bring NeuroSTAT to the market for treatment of moderate to severe traumatic brain injury, including the design of the planned Phase IIb proof of concept study with NeuroSTAT. The EMA Scientific Advice feedback is supportive of the novel design NeuroVive has proposed for its efficacy studies, including advanced imaging assessments of the protective effect of NeuroSTAT on brain cells. Furthermore, a subpopulation of the patient population will be selected with similar types of injury to the brain which facilitates evaluation of efficacy. • On May 23, 2017, NeuroVive Pharmaceutical announced results from clinical and preclinical studies with NeuroSTAT® for the prevention of the sequelae of traumatic brain injury (TBI). The combined positive outcome of the results from the clinical phase IIa CHIC (Copenhagen Head Injury Cyclosporine) study, conducted at Rigshospitalet in Copenhagen, Denmark, and the preclinical studies, done in collaboration with the University of Pennsylvania (Penn), USA, have now convinced NeuroVive to proceed into the next stage of clinical development. The company has therefore decided to close the CHIC study in advance and focus its TBI project efforts on preparing for the next clinical study with NeuroSTAT for TBI. The results of the open label CHIC study show that appropriate dose-dependent concentration levels can be measured in the blood, and that NeuroSTAT reaches the target, the central nervous system (CNS). No unexpected safety signals were detected. Thus, the primary objective of CHIC to demonstrate safety and elucidate pharmacokinetics of NeuroSTAT at two different dose levels (5 and 10 mg/kg/day) in patients with severe TBI has been reached. A significantly reduced volume of brain injury (35% decrease) after NeuroSTAT treatment was observed in MRI scans in the experimental TBI studies done in collaboration with Penn. Furthermore, these studies displayed positive changes in brain energy metabolite levels and mitochondrial respiratory function, as well as decreased generation of reactive oxygen species. In collaboration with Penn, NeuroVive has also evaluated the effect of NeuroSTAT in a non-clinical experimental TBI model. A total of three substudies have successfully been conducted and completed. Positive results from the first two substudies established the pharmacokinetic profile of NeuroSTAT in blood, CSF and brain in the disease model, and showed that NeuroSTAT dose-dependently crosses the blood-brain barrier. The third and final sub study evaluated several different efficacy parameters related to mitochondrial function and metabolism, as well as advanced translational brain imaging MR techniques important in the design of the next clinical study.

Is general: Yes