Stanford University starts recruiting participants for swine flu vaccine clinical trial

Aug 31 2009

The Stanford University School of Medicine is recruiting participants for a clinical trial to determine the safety of an experimental vaccine against the new H1N1 strain of influenza when the vaccine is combined with an immune-stimulating substance called an adjuvant. The trial will also examine whether use of the adjuvant improves the immune response to the vaccine.

Most people’s immune systems have never been exposed to any influenza strain closely related to the H1N1 strain, which first began to surface last spring, said Cornelia Dekker, MD, professor of pediatrics and medical director of the Stanford-LPCH Vaccine Program. The novel virus thus has spread quickly, giving rise to a pandemic that has governments around the world scrambling to plan mass-vaccination strategies as a public-health measure.

Early-phase trials, whose primary goals are to determine the safety of the vaccine given by itself and to examine the immune response after one and two doses, are already under way at several centers throughout the country.

Unlike other trials to date, the one at Stanford will test a version of the vaccine that contains an adjuvant: a substance that stimulates the immune system so that it attacks the virus more vigorously. It is possible that the addition of the adjuvant might allow the dose of vaccine to be lowered, thus allowing more people to be immunized, Dekker said. Use of an adjuvant may also provide a higher immune response in persons who do not respond as well to the vaccine alone, such as the elderly. Both of these possibilities will be tested in this trial.

Dekker is the principal investigator at the Stanford site, one of six throughout the country where the vaccine is being tested in the phase-2 trial sponsored by the National Institutes of Health.

Prospective participants are encouraged to visit a dedicated Web site, http://vaccines.stanford.edu/clinical_trials.html, to review study information and join the volunteer mail list, or call (650) 498-7284 to learn more about their potential eligibility for the trial. Dekker noted that people considering participation in the trial should be prepared to make eight separate visits to the Stanford campus, to receive two vaccine doses spaced three weeks apart, undergo several blood draws and engage in four phone conversations with study staff over a 13-month time frame. (Enrolled subjects will receive parking vouchers for their visits and compensation for their time.)

“We’re hoping to get as many as 130 volunteers enrolled at the Stanford site within a very short time,” said Dekker. Prospective subjects must all be at least 18 years old and in general good health. The trial design calls for two-thirds of the selected participants to be in the 18-64 age category, with the remainder drawn from the 65+ population.

The candidate vaccine being tested in this study is manufactured by the same method used to make the seasonal-influenza vaccine. All of the participants in the Stanford study will receive the vaccine, although at different doses and with or without the adjuvant. Subjects will be randomly assigned to one of five different groups. Three groups will get different doses of the H1N1 virus vaccine combined with adjuvant. The two other groups will receive the higher doses of vaccine, but no adjuvant. Neither the volunteers nor the study staff will know which vaccine dose or combination was given to whom until the end of the study. The adjuvant used in this study has been tested with other influenza vaccines in more than 12,000 persons, but this will be the first time it is given combined with this particular vaccine.

The spread of the pandemic H1N1 influenza strain is expected to kick into higher gear this fall as children transmit the virus to one another in school. Meanwhile, the federal government is awaiting word from trials already under way before making a final decision about whether to proceed with a large-scale national immunization program.

The government, which had hoped to have 120 million doses of the H1N1 vaccine on hand by Oct. 15, announced on Aug. 18 that, because of delays in the manufacturing process, it now expects only 45 million doses to be available by then.

Clearly, innovations that might increase the vaccine’s potency would be helpful, Dekker said. An adjuvant that can boost overall immune response is potentially “dose-sparing”: Its inclusion in a vaccine may render the vaccine potent in smaller doses, stretching tight supplies to cover more people. Dekker said data from this trial will help the U.S. government determine whether to include an adjuvant in the vaccine in order to stretch tight supplies or to boost the immune response.