NIH Watch [to 7 February 2015]
http://www.nih.gov/news/index.html

:: Ebola Vaccine Trial Opens in Liberia
Study Led by Liberia-NIH Partnership Will Test Two Experimental Vaccines
Feb. 2, 2015
A large clinical trial to assess the safety and efficacy of two experimental vaccines to prevent Ebola virus infection is now open to volunteers in Liberia. The trial is being led by a recently formed Liberia-U.S. clinical research partnership and is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The Partnership for Research on Ebola Vaccines in Liberia or PREVAIL, a Phase 2/3 study, is designed to enroll approximately 27,000 healthy men and women aged 18 years and older.

One vaccine candidate, cAd3-EBOZ, uses a chimpanzee-derived cold virus to deliver Ebola virus genetic material from the Zaire strain of virus causing the outbreak in Liberia. Published interim results from a Phase 1 trial of this vaccine, which was co-developed by NIAID scientists and GlaxoSmithKline, provided necessary safety information and showed that it prompted immune responses to the outer coat of Ebola virus. The other candidate, VSV-ZEBOV, employs vesicular stomatitis virus, an animal virus that primarily affects cattle, to carry an Ebola virus gene segment. The VSV-ZEBOV vaccine was developed by the Public Health Agency of Canada and licensed to NewLink Genetics Corporation through its wholly owned subsidiary BioProtection Systems Corporation. Phase 1 trial results of this vaccine also provided safety information and showed that it prompted immune responses to the outer coat of Ebola virus. These results have not yet been published but were made available to the regulatory bodies reviewing the study.

“The scale of the current Ebola outbreak in West Africa is unprecedented, and specific medical countermeasures are needed for this and future outbreaks,” said NIAID Director Anthony S. Fauci, M.D. “It is imperative that any potential countermeasures, including vaccines, be tested in a manner that conforms to the highest ethical and safety standards in clinical trials designed to provide a clear answer to the question of whether a candidate vaccine is safe and can prevent infection. This trial is designed to provide such answers.”

In addition to healthy adults in the general population, the trial will seek volunteers from groups at particular risk of Ebola infection, including health care workers, communities with ongoing transmission, contact tracers and members of burial teams. Social mobilization and community engagement activities began in Montserrado County, where the Liberian capital Monrovia is located, before the trial started and will continue in order to successfully recruit thousands of participants.

Participants will be assigned at random to one of three equal-sized groups. Volunteers in one group will receive a placebo (saline) injection, while the others will receive a single injection of either the cAd3-EBOZ vaccine or the VSV-ZEBOV vaccine. In addition to including a placebo group, the trial will be double-blinded, meaning that neither volunteers nor staff will know whether a vaccine or placebo was administered. A randomized, double-blind, placebo-controlled trial is considered the “gold standard” in clinical research. All participants will be advised on how to minimize the risk of becoming infected with Ebola virus and will be contacted by study staff about one week after the injection and then monthly for the duration of the study, which is currently expected to last about twelve months.

Given the current decline in the number of new Ebola cases in Liberia, study investigators anticipate the need for flexibility in the conduct and design of the trial to address the changing nature of the outbreak.

The co-leaders of the trial are Stephen B. Kennedy, M.D., MPH, secretary-general of the Liberia College of Physicians and Surgeons; Fatorma Baloy, Ph.D., director, Liberian Institute for Biomedical Research; and H. Clifford Lane, M.D., NIAID’s deputy director for clinical research and special projects. The pharmaceutical company GlaxoSmithKline (Research Triangle Park, North Carolina) will supply the cAd3-EBOZ investigational vaccine; Merck (Kenilworth, New Jersey) and NewLink Genetics, Inc. (Ames, Iowa) will supply the VSV-ZEBOV candidate. Additional information about the study is available at ClinicalTrials.gov using the identifier NCT02344407.

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Chimerix Focusing Efforts on CMV and Adenovirus Pivotal Trials
Brincidofovir Will Not Be Considered in Further Clinical Trials in Ebola Virus Disease
DURHAM, N.C., Jan. 30, 2015 (GLOBE NEWSWIRE) — Chimerix, Inc. (Nasdaq:CMRX), a biopharmaceutical company developing novel, oral antivirals in areas of high unmet medical need, today announced that after discussion with the U.S. Food and Drug Administration, the company is ceasing further participation in all current and future clinical studies of brincidofovir for Ebola Virus Disease (EVD), including the study announced in December in Liberia sponsored by investigators at the University of Oxford and the supportive Phase 2 study of brincidofovir for EVD, Study 205.

Over the last several weeks the number of new cases of confirmed Ebola Virus Disease in Liberia has decreased significantly, with only a handful of patients enrolled to date in the single-arm study of brincidofovir led by the University of Oxford and ISARIC (International Severe Acute Respiratory and Emerging Infection Consortium) with operational support from Médecins Sans Frontières (MSF).

The decision to cease further study of brincidofovir in individuals with Ebola Virus Disease does not impact the company’s continued focus on advancing brincidofovir in pivotal studies of CMV prevention in recipients of allogeneic hematopoietic transplant and for the treatment of adenovirus infection in immunocompromised patients.

“We were honored to be able to work with the researchers at University of Oxford and ISARIC together with MSF to initiate the first clinical trial of an investigational agent during an outbreak. The progress in controlling the Ebola outbreak in Liberia is to be commended,” said M. Michelle Berrey, MD, MPH, President and CEO of Chimerix. “Chimerix will continue to push forward with our development of brincidofovir for the prevention and treatment of serious viral infections in transplant recipients and other immunocompromised patients.”

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MSF/Médecins Sans Frontières [to 7 February 2015]
Selected Press Releases/Field News
Ebola Drug Trial in Liberia Halted
February 04, 2015
BRUSSELS/NEW YORK—A trial of the experimental Ebola drug brincidofovir in Liberia has officially ended due to a significant drop in the number of new Ebola cases and the drug manufacturer’s decision to withdraw from the trial, the international medical humanitarian organization Doctors Without Borders/Médecins Sans Frontières said Tuesday.

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Ebola Drug Aids Some in a Study in West Africa
By SHERI FINK
New York Times
February 4, 2015
[Excerpt]
For the first time, a drug is showing promising signs of effectiveness in Ebola patients participating in a study. The medicine, which interferes with the virus’s ability to copy itself, seems to have halved mortality — to 15 percent, from 30 percent — in patients with low to moderate levels of Ebola in their blood, researchers have found. It had no effect in patients with more virus in their blood, who are more likely to die.

The drug, approved as an influenza treatment in Japan last year, was generally well tolerated.
“The results are encouraging in a certain phase of the disease,” Dr. Sakoba Keita, director of disease control for the Guinean Ministry of Health, said in a telephone interview. The drug is being tested in Guinea, one of the three West African countries most affected by the Ebola crisis.

The details of the early findings have not yet been announced, but they raise questions about which patients, if any, outside the study should be offered treatment with the drug, favipiravir. “These are very difficult, agonizing decisions,” said Susan Ellenberg, a professor of biostatistics at the University of Pennsylvania’s Perelman School of Medicine, who was not involved in the research. She cautioned that early results were sometimes not borne out.

The drug has been provided on an emergency basis to Ebola patients in European countries, but not in Africa. The Japanese maker of the drug announced in October that it had 20,000 courses of treatment in stock. The epidemic is now ebbing but is not over. The World Health Organization on Wednesday reported 124 new cases in Guinea, Sierra Leone and Liberia in the week that ended on Sunday, warning of an increased geographical spread in Guinea and a rise in new cases in all three countries for the first time this year.

Early reports of the interim results of the drug trial have created unanticipated complications, delaying the testing of at least one other therapy as researchers reconsidered plans and some doctors pressed to make favipiravir more widely available.

Researchers and health authorities have been quietly debating whether and when to release the preliminary results of the study. The dilemmas they face echo those from the early years of the AIDS epidemic. Because mortality was so high in a disease with no proven treatment, there was demand to provide experimental therapies to everyone.

The results for the drug favipiravir are based on an analysis of 69 patients older than 14 who have received it at two sites in Guinea since December. The survival rates of those with low to moderate levels of virus in their blood were significantly better than those of patients previously treated at a center run by Doctors Without Borders in Guéckédou, Guinea….