A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial.

Related collections

Most cited references 8

Record: found
Abstract: found
Article: found

Is Open Access

Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates

Kristen E Pascal, Drew Dudgeon, John Trefry … (2018)

Abstract Background For most classes of drugs, rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety, and pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases. Methods In this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses. Results Of the antibody clones isolated, 3 were selected as best at neutralizing EBOV and triggering FcγRIIIa. Binding studies and negative-stain electron microscopy revealed that the 3 selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments. When combined, a single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent. Conclusions This antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities, and demonstrates high-level postexposure protection from lethal EBOV disease in NHPs. It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.

0 comments Cited 79 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Blood chemistry measurements and D-Dimer levels associated with fatal and nonfatal outcomes in humans infected with Sudan Ebola virus.

Anthony Sanchez, Daniel Bausch, P. ROLLIN (2007)

Blood samples from patients infected with the Sudan species of Ebola virus (EBOV), obtained during an outbreak of disease in Uganda in 2000, were tested for a panel of analytes to evaluate their clinical condition and to compare values obtained for patients with fatal and nonfatal cases and for uninfected (hospitalized control) patients. Liver function tests showed higher levels of aspartate aminotransferase (AST) in blood samples from patients with fatal cases than in samples from patients with nonfatal cases, whereas alanine aminotransferase levels were comparable and only slightly increased in all patients, suggesting that increased blood AST levels are due to a greater degree of injury in tissues other than the liver. Significantly higher levels of amylase, urea nitrogen, and creatinine suggest that acute pancreatitis and renal dysfunction develop in fatal cases, whereas reduced albumin and calcium levels may be linked to these conditions or to liver damage. d-Dimer levels in blood specimens were drastically increased in patients with fatal and nonfatal infections but were 4 times higher in patients with fatal cases than in patients who survived (180,000 vs. 44,000 ng/mL), during the most acute period of the infection (6-8 days after onset). These results indicate that disseminated intravascular coagulation is an early and important component of EBOV disease. This study has identified levels of analytes with prognostic value, which can also be used to target therapeutic interventions, and expands on the findings of prior blood tests conducted on this group of patients.

0 comments Cited 61 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study

Martin Gaudinski, Emily Coates, Laura Novik … (2019)

mAb114 is a single monoclonal antibody targeting the receptor binding domain of Ebola virus glycoprotein that prevents mortality in rhesus macaques treated after lethal challenge with Zaire ebolavirus . We present expedited data from a phase 1 study to evaluate mAb114 safety, tolerability, pharmacokinetics, and immunogenicity. VRC 608 is a phase 1, dose-escalation study performed at the National Institutes of Health (NIH) Clinical Center. Healthy adults ages 18-60 were sequentially enrolled into dose groups of 5, 25, and 50 mg/kg and infused intravenously (IV) with mAb114 over 30 minutes and followed for 24 weeks. Safety and tolerability were assessed through soliciting infusion site and systemic symptoms by self-reporting, direct clinician assessment, and clinical laboratory data. All participants have completed the 28 day adverse event reporting period and are currently either in long-term follow up or have completed study visits. The primary study outcome was safety and tolerability, with pharmacokinetic and anti-drug antibody evaluation as secondary objectives. Nineteen participants were enrolled between May 16, 2018, and September 27, 2018. One participant was not infused because intravenous access was not adequate. Eighteen participants received a single infusion of 5 mg/kg (n=3), 25 mg/kg (n=5), or 50 mg/kg (n=10) of mAb114. All infusions were well tolerated at infusion rates between 209-375 mL per hour over 30-37 minutes with zero infusion reactions or rate adjustments. No participants had infusion site symptoms. Systemic symptoms were all mild and present only in 22% of participants across all dosing groups. There were no unsolicited adverse events (AEs) related to mAb114 and one serious adverse event (SAE) unrelated to mAb114. mAb114 has linear pharmacokinetics and a half-life of approximately 24 days with no evidence of anti-drug antibody development. mAb114 was well-tolerated, demonstrated linear pharmacokinetics, and was easily and rapidly infused making it an attractive and deployable option for treatment in outbreak settings. The VRC 608 clinical trial was supported by the intramural research program of the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), NIH. mAb114 production was funded by the Defense Advanced Research Projects Agency.