August 31, 2015
Edge Therapeutics has reported results of
a phase I/II study of EG-1962 for aneurysmal
subarachnoid hemorrhage (aSAH) resulting
from a ruptured brain aneurysm. The
NEWTON trial evaluated six dose-cohorts
(100, 200, 400, 600, 800, and 1,200mg).
The primary endpoint was to establish
the maximum tolerated dose, which has
been determined to be 800mg. Safety and
tolerability data are available for all six
cohorts, while EG-1962 efficacy results are
reported for only five cohorts, as the sixth
cohort (1,200mg) was not a tolerable dose.
Exploratory endpoints measuring outcome
results from the 90-day follow-up available
demonstrated that 60% (27 of 45) of
patients treated with EG-1962 experienced
a favorable outcome (a score of 6 to 8) as
measured by the extended Glasgow Outcomes
Scale (GOSE). By contrast, the 90-day
favorable outcome rate for patients treated
with the current standard-of-care, oral
nimodipine, was only 28% (5 of 18). (The
GOSE is a clinically validated 8-point scale—
1=death; 8=good recovery—used to assess
recovery for patients who have suffered a
ruptured aneurysm. A favorable outcome
in the NEWTON trial protocol is defined as a
GOSE score of six or greater as measured 90
days after aSAH.) In addition, improved efficacy
was supported by a reduction in vasospasm,
delayed cerebral ischemia and use of
rescue therapies. Safety results show that no
patients (zero of 54) experienced EG-1962
related hypotension, while 17% of patients
(three of 18) treated with oral nimodipine,
the current standard-of-care, experienced
October 24, 2011
The Medicines Company released results from a phase IIa trial of MDCO-2010, under development for the reduction of blood loss during surgery. This randomized, double-blind, placebo-controlled study enrolled 32 subjects undergoing elective, primary coronary artery bypass graft surgery. The subjects received one of five MDCO-2010 doses or placebo infused immediately after heparin bolus until sternal closure. Blood loss was measured by the amount of blood drained via chest tubes at 12 hours postoperatively. The median chest tube drainage in the placebo arm was 900 mL versus 350 mL, 350 mL and 360 mL, respectively in the three highest MDCO-2010 cohorts (p<0.025). The subjects in these arms also had less transfusion requirements as compared to placebo.
September 6, 2010
Sangart released positive results from a phase IIa trial evaluating MP4OX for the reduction of lactic acidosis due to hemorrhagic shock following severe trauma. This randomized, double-blind, controlled study enrolled 51 subjects with trauma-induced severe hemorrhagic shock across sites in the United Kingdom, Germany, France and South Africa. The subjects received MP4OX 250 mL or 500 mL or Ringer's Lactate solution 500 mL. Data showed a statistically significant greater immediate and sustained decrease of lactic acid in the MP4OX treatment arms compared to the control arm. A greater proportion of subjects treated with MP4OX were able to attain normal lactate levels as early as four hours post-treatment. In addition, data showed a strong trend toward outcomes benefits through multiple measures, including reducing the average total number of days spent in hospital. Serious adverse events were comparable between the MP4OX-treated and control groups.
October 27, 2008
AstraZeneca released positive results from a clinical trial of Nexium (esomeprazole) for the treatment of peptic ulcer re-bleeding. This study enrolled 767 subjects across Europe, Africa and Asia who had received successful endoscopic treatment to stop peptic ulcer bleeding. The subjects were randomized to first receive an intravenous (i.v.) infusion of esomeprazole 80 mg over 30 minutes followed by 8 mg i.v./hour for 72 hours, and then receive 40 mg oral treatment for 27 days. A parallel placebo-controlled group received an i.v. infusion of placebo before the same 27-day period of oral treatment with esomeprazole. The results of the study demonstrated that statistically significantly fewer subjects treated with esomeprazole experienced ulcer re-bleeding compared with placebo both at 72 hours (5.9% versus 10.3%, P=0.026) and at seven days (7.2% versus 12.9%, P=0.0096). When examined over a 30 day period, esomeprazole was shown to significantly reduce the number of subjects re-bleeding by almost half compared to placebo (7.7% versus 13.6%, P=0.0092). In addition, all subjects receiving esomeprazole required significantly fewer interventions by day 30, with 6.4% needing endoscopic re-treatment compared with 11.6% in the placebo group (P=0.037). Overall, the esomeprazole group required significantly fewer days in hospital due to re-bleeding compared to the placebo group (284 days versus 500 days, P=0.008). Regulatory filings are currently under review by the FDA and EMEA.
October 13, 2008
OMRIX reported positive interim results from a phase II trial of Evicel, a Patch for the treatment of mild to moderate bleeding during surgery. This randomized, controlled study planned to enroll up to 210 subjects in the United States who were treated with Evicel or Surgicel, the current standard of care. To date 90 subjects have been enrolled and treated. Evicel was superior to Surgicel in the primary efficacy endpoint, which measured the proportion of subjects achieving hemostatic success at 4 minutes after randomization with no re-bleeding requiring treatment during a subsequent 6-minute observation period. In accordance with the study protocol, since superiority was established, randomization has been stopped and additional non-randomized subjects are undergoing enrollment and treatment with Evicel.
March 5, 2007
Novo Nordisk released negative results from a phase III trial of NovoSeven for the treatment of Intracerebral Hemorrhage (ICH). This international, randomized, double-blind, placebo-controlled trial enrolled 821 subjects who were suffering from spontaneous ICH as confirmed by a CT scan. Subjects received either NovoSeven or placebo within four hours of symptom onset, in addition to conventional treatment. Treatment was safe and well tolerated. Efficacy results revealed that NovoSeven significantly reduced intracerebral bleeding compared to placebo. In addition, improvements in functional independence and neurological impairment were observed on day 15. However the primary endpoint, improvement in mortality and severe disability at day 90, was not achieved. Based on the results, Novo Nordisk has decided not to seek FDA approval of NovoSeven for this indication.
September 11, 2006
Zymogenetics issued positive results from a phase III trial of rhThrombin for the treatment of blood loss during surgery. This multiple site, randomized, double-blind, controlled trial enrolled 400 subjects undergoing surgery. Subjects were randomized in a 1:1 ratio to receive rhThrombin (1000 U/mL) or bovine thrombin (1000 U/mL). During the surgical procedure subjects were treated with one of the two study drugs, in combination with an absorbable gelatin sponge, at appropriate bleeding evaluation sites. The primary outcome was time to hemostasis when compared to currently approved bovine-derived thrombin, measured by incidence of hemostasis within 10 minutes. The trial met the primary endpoints, with hemostasis occurring within 10 minutes in both treatment groups. Secondary endpoints were met as well with adverse effects comparable between the two groups and the rate of antibody formation at 1.5% in the rhThrombin group, versus 22% for those treated with the bovine thrombin product (p < 0.0001). ZymoGenetics plans to submit a Biologics Licensing Application for rhThrombin to the FDA in late 2006.
August 14, 2006
Inspire Therapeutics reported negative results of a phase II trial of INS50589, a platelet aggregation inhibitor, for the treatment of post-operative bleeding complications following coronary artery bypass surgery. This randomized, double-blind trial enrolled 160 subjects undergoing coronary artery bypass graft surgery. Subjects were to receive three intravenous doses of INS50589, or placebo, at 0.2, 0.5, and 1 mg/kg/hour. Interim analysis obtained from 27 treated subjects revealed that safety endpoints were not achieved, as a range of bleeding complications was observed. Based on this data, an independent Data Monitoring Committee recommended that the trial be terminated at all dose levels. Inspire had no plans to further develop INS50589 at this time.
March 20, 2006
Renovis and AstraZeneca announced preliminary results of a phase IIb trial, dubbed CHANT, of Cerovive (NXY-059) for the treatment of acute intracerebral hemorrhage (ICH). Safety and tolerability data were generally positive, with comparable overall mortality rates (roughly 20%) for subjects receiving the drug and placebo. Secondary outcomes yielded similar results, with no significant difference between the drug and placebo in stroke outcomes following ICH. This multi-center, double-blind, placebo-controlled, parallel group study enrolled 603 patients across 20 countries, who were randomized to receive a 72 hour infusion of NXY-509 or placebo, initiated within 6 hours of ICH onset.
August 29, 2005
ZymoGenetics reported aggregate results of four-phase II trials of their recombinant human Thrombin (rhThrombin) being investigated to control bleeding during surgery. Combined results showed product appeared to be safe and well tolerated, with a favorable immunogenicity profile. The trial enrolled 130 subjects undergoing various procedures including spinal surgery, liver section, peripheral artery bypass, or arteriovenous graft construction. The results were presented at The International Society on Thrombosis and Haemostasis annual meeting in Sydney, Australia. The company also announced it is finalizing its plans for a phase III pivotal trial for late 2005.
July 5, 2004
Novo Nordisk has announced positive results of their phase IIb study of NovoSeven for the treatment of intracerebral hemorrhage (ICH). NovoSeven is currently approved as a treatment for acute bleeding in hemophilia. Results have shown that the drug led to a significant reduction in hematoma growth, compared to placebo, and significantly improved neurological and functional outcomes following an ICH incident. The double-blind, dose-response study enrolled a total of 400 subjects in 20 countries; subjects with spontaneous ICH confirmed by CT scan within three hours of symptom onset randomized to receive either NovoSeven or placebo, in addition to standard therapy. Follow-up CT scans, performed at 24 and 72 hours, found that NovoSeven significantly and dose-dependently reduced hematoma expansion, and observations at 15 and 90 days found significant improvement in severity score on neurological function tests in the NovoSeven group. Novo Nordisk announced plans to file supplementary regulatory submissions based upon this data.
July 21, 2003
ZymoGenetics reported positive results from a phase I trial investigating recombinant human Factor XIII (rFactor XIII) for the treatment of bleeding complications associated with congenital and acquired Factor XIII deficiencies. Result indicated that the expected dose-response relationship predicted from animal studies was observed, with a rise in rFactor XIII levels to 191% of normal in the highest dose group. No serious adverse events were reported and the most common side effect observed was headache. The double blind, placebo controlled, single-dose escalation study was designed to evaluate the safety and pharmacokinetics of rFactor XIII in healthy volunteers. Subjects were given a single intravenous injection (2 U/kg to 50U/kg), and then monitored for 28 days.