Infectious Diseases Clinical Trials

Lung allograft recipients have a higher burden of influenza disease and greater associated morbidity and mortality compared with healthy controls. Induction and early maintenance immunosuppression is thought to impair immunogenicity to standard dose inactivated influenza vaccine. This early post-transplant period is when immunity is most desirable, since influenza disease during this time frame is associated with adverse consequences. Thus, strategies to reduce severe influenza disease in this highly susceptible population are critical. No trials in lung transplant recipients have evaluated two doses of HD-IIV within the same influenza season as a strategy to improve immunogenicity and durability of influenza prevention. Furthermore, no influenza vaccine trials have focused on enrollment of subjects at early post-transplant timepoints. Very few studies have been performed in solely lung allograft recipients. Immunosuppression intensity is highest in lung patients, thereby limiting comparisons to recipients of heart, liver, and kidney transplants. Therefore, studies to assess both HD-IIV and two-dose strategies in the same influenza season in post-lung transplant recipients are greatly needed.

The central hypothesis of our proposal is that lung allograft recipients who are 1-35 months post-transplant and receiving two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have higher HAI geometric mean titers (GMT) to influenza antigens compared to those receiving two doses of SD-QIV. To test this hypothesis and address the above critical knowledge gaps, we propose to conduct a phase II, multi-center, randomized, double-blind, controlled immunogenicity and safety trial comparing the administration of two doses of HD-QIV to two doses of SD-QIV in lung allograft recipients 1-35 months post-transplant. The results of this clinical trial will address significant knowledge gaps regarding influenza vaccine strategies (e.g., one vs. two doses and HD-QIV vs. SD-QIV) and immune responses in lung transplant recipients and will guide vaccine recommendations during the post-transplant period.

This study is looking to see if an investigational anti-HIV vaccine is safe and well-tolerated in people living with HIV. The study is also trying to find out if the vaccine can help the immune system work against HIV. It is given as one injection, similar to a flu shot, in each upper arm five times over one year (ten injections total). Study participants will have a 2:1 chance of receiving the active vaccine vs. placebo.

Having trouble taking your HIV medication every day? If daily HIV treatment is not working well for you, you are not alone. The CROWN study is part of the effort to find more options for people whose HIV is not undetectable despite treatment. Researchers are looking into a potential injectable HIV treatment option to see how effective it may be

compared to oral ART that has not provided undetectable HIV. If you choose to join this clinical study, you will play a key role in advancing HIV research.

If eligible, you will be assigned by chance to a study treatment group.

• Group 1 (3-in-4 chance): study drug injections once every 2 months after 2, once-monthly starter doses
• Group 2 (1-in-4 chance): oral antiretroviral therapy (ART) for 6 months followed by study drug injections once every 2 months after 2, once-monthly starter doses
• Having some participants take oral ART for 6 months before they switch to the study drug helps researchers compare the two options.

The CROWN study includes 20 scheduled visits over 2 years. You will have tests and procedures at visits to check your health. You will also receive study treatment for up to 2 years. Support may be available to help arrange travel to visits or reimburse you for some costs.