Phase 1 Clinical Trial to Assess if a Topical Cream Can Enhance Response to H5N1 Flu Vaccine

The World Health Organization estimates that since 2003, there have been 860 cases of H5N1 influenza, 454 of which were fatal. As with all influenza strains, investigators are worried about H5N1’s ability to mutate and potentially become more easily transmissible amongst humans, which could lead to a pandemic situation.

In an effort to prevent a pandemic before it happens, investigators have launched a phase 1 clinical trial to assess whether imiquimod, a topical cream typically used to treat genital warts and certain skin cancers, can enhance immune responses to H5N1 virus vaccines.

“Imiquimod boosts the immunity by directly activating the body’s immune cells,” Hana M. El Sahly, MD, associate professor of molecular virology and microbiology, Baylor College of Medicine and principal investigator for the clinical trial, told Contagion®. “It is the reason why imiquimod helps get rid of warts, for example. It allows the body’s immune system to fight off the virus that caused the wart. In the case of a vaccine, we are testing to see if boosting the immune cells while giving the H5N1 flu vaccine will result in improved immune responses to the vaccine itself.”

The trial is underway at Baylor College of Medicine, a part of the Vaccine and Treatment Evaluation Units (VTEUs), a network of research sites evaluating experimental vaccines against infectious diseases that is funded and managed by the National Institute of Allergy and Infectious Diseases (NIAID) part of the National Institutes of Health (NIH).

The trial is enrolling 50 participants aged 18 to 50 years in a randomized double-blind trial. The participants will receive an H5N1 vaccine that was designed for use in a pandemic. The vaccine is made from an inactivated influenza virus and was approved by the US Food and Drug Administration (FDA) in 2007.

The participants will be randomly assigned to 1 of 2 test groups, both of which will receive 2 intradermal doses of the FDA approved H5N1 vaccine 21 days apart.

One group will receive the FDA-approved imiquimod cream applied to their upper arm before each vaccination. The cream is rubbed into the skin so that it is fully absorbed and after a 5-15-minute waiting period, the vaccine is administered to the sport where the cream was applied.

Participants in the control group will receive an aqueous placebo cream instead of the imiquimod cream prior to vaccination with the H5N1 virus vaccine.

Both groups will be evaluated by clinicians for any reactions such as injection site redness or swelling, along with fever, headache and nausea.

Additionally, participants will return to the clinic regularly over the 7 months following the vaccinations for blood tests to determine the immune response. Participants will also be required to record any symptoms and medications taken at home in a diary.

Imiquimod cream activates the innate immune system, the body’s immediate defense against invading pathogens. Investigators are hopeful that the immune boosting properties of imiquimod could stretch the supply of the H5N1 vaccines because fewer doses would be required to achieve immunity; therefore, more individuals could be vaccinated in an outbreak or pandemic setting.

Imiquimod has received favorable results in recent clinical trials. In Hong Kong, investigators launched 2 clinical trials — one that enrolled elderly participants and the other that enrolled young adults. These trials found that imiquimod cream was generally well-tolerated. According to investigators, applying the cream before vaccination generated significantly more robust immune responses that the control groups that did not receive imiquimod.

The first participant in this phase 1 clinical trial was vaccinated in June of 2018 and investigators expect early results by the end of 2018.