Phases of Clinical Trials

After an experimental vaccine has been tested in laboratory and animal studies to determine its safety and immune response, it must successfully complete three stages of testing in people before it can be licensed.

Stages of Vaccine Testing in Humans

Phase	Number of Participants	Primary Rationale
I	20-100	Safety
II	Hundreds	Safety and Immunogenicity (required for Phase III)
III	Thousands	Safety and Effectiveness (required before licensure)

A Phase I trial is the first setting where an experimental HIV vaccine is given to people. Such a trial usually enrolls about 20 to 100 HIV-negative volunteers. A Phase I trial primarily seeks information on safety, looking for any vaccine-related side effects. This is done by comparing the vaccine with a control or placebo (an inactive substance, such as normal saline). A Phase I trial can also provide initial data on the dose and administration schedule (the time between vaccinations) that achieve the optimal immune response. Scientists may also be able to analyze results to determine if the vaccine will have an effect against different variations of HIV found around the world. The HVTN's Phase I trials, as well as Phase II and III trials, are randomized and double-blinded. Neither the participant nor the clinician know who has received a vaccine or placebo. A Phase I trial typically lasts 12 to 18 months.	20-100 in Phase I
Once Phase I trials show the experimental HIV vaccine to have a baseline of safety, it can advance into Phase II trials for further safety testing. Phase II trials enroll up to several hundred people. These trials still focus on safety, but researchers gather more in-depth information about the human immune response and further data on the most effective dose and administration schedule. A Phase II trial can last two to three years.	Hundreds in Phase II
The most promising experimental vaccines then move into Phase III trials. These trials enroll thousands of HIV-negative volunteers. Phase III trials are designed to answer the question of whether or not a vaccine is effective in preventing HIV infection. Phase III data indicating a vaccine's safety and effectiveness in large numbers of people is required to support a licensure application to the Food and Drug Adminstration (FDA). A Phase III trial can take three to five years to complete. Experimental vaccines used in all phases of testing are not produced from live virus or from HIV-infected human cells. Volunteers cannot get HIV infection or AIDS by receiving an experimental vaccine.	Thousands in Phase III