Vaccination against human papillomavirus (HPV) after allogeneic stem cell transplantation, a randomized study between early and late vaccination.

The primary objective of this study is to compare the **vaccine** responses to Gardasil 9® in recipients of allogeneic stem cell transplantation, focusing on the timing of vaccination. The study evaluates the efficacy of initiating vaccination at 9 months post-transplantation (early) versus 15 months post-transplantation (late). This comparison is clinically relevant as it may inform optimal vaccination timing to enhance immune response and protection against human papillomavirus (HPV) in this vulnerable population.

Secondary objectives include:

• Assessing antibody levels against all nine HPV types included in the vaccine at 1 month and 12 months after completion of vaccination, comparing early versus late vaccination.
• Determining the proportion of participants who are seronegative or seropositive against the nine HPV types at 1 and 12 months post-vaccination, comparing early versus late vaccination.
• Evaluating seroconversion rates against the nine HPV types from pre-vaccination to 1 month post-vaccination, comparing early versus late vaccination.
• Assessing the proportion of participants who are seropositive against 7 out of 9 serotypes in the vaccine at 1 and 12 months post-vaccination, comparing early versus late vaccination.

The clinical trial involves **recipients of allogeneic stem cell transplantation** and aims to compare vaccine responses to Gardasil 9® at different post-transplant intervals. The study population includes both male and female adults aged 18 to 45 years. Participants are selected based on their status as recipients of allogeneic stem cell transplants from either related or unrelated donors. The trial does not restrict participation based on prior HPV vaccination status before transplantation. The sponsor has not provided information regarding the total number of participants. The study does not specifically target a vulnerable population, and no particular lifestyle considerations such as diet or physical activity are highlighted as part of the trial's focus.

The clinical trial is designed to evaluate the **vaccine** responses to Gardasil 9 in recipients of allogeneic stem cell transplantation. This study is a randomized, controlled, double-blind trial comparing early versus late vaccination post-transplant. The primary objective is to assess the antibody levels against **HPV 16** one month after the third vaccine dose, with secondary endpoints including antibody levels against all nine HPV serotypes at various time points. The trial is expected to commence on October 1, 2024, and conclude by January 31, 2029, with a total duration of approximately five years.

Participants will undergo a series of study visits, beginning with an inclusion visit to confirm eligibility based on criteria such as age (18-45 years) and prior HPV vaccination status. The inclusion visit will involve screening procedures to ensure participants meet all necessary conditions for trial participation. Following the inclusion visit, participants will receive the vaccine intramuscularly in a series of doses, with follow-up visits scheduled to monitor antibody responses and overall health. These follow-up visits will occur at one month and twelve months after the third vaccine dose to evaluate the primary and secondary endpoints.

The expected length of participant involvement is approximately 18 months, covering the period from initial vaccination to the final follow-up visit. Conditions that may lead to early termination from the study include adverse reactions to the vaccine or withdrawal of consent by the participant. The trial is categorized as a Phase 4 study, indicating it is conducted after the vaccine has been approved for public use, focusing on further evaluating its effectiveness and safety in a specific population. The study aims to provide valuable insights into the optimal timing of HPV vaccination in this patient group, contributing to improved post-transplant care.

The clinical trial involves the administration of **Gardasil 9**, a **suspension for injection** formulated as a **Human Papillomavirus (HPV) 9-valent Vaccine (Recombinant, adsorbed)**. This vaccine is designed to protect against nine types of HPV, specifically types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The active substances in the vaccine are the L1 proteins of these HPV types, which are structurally diverse substances classified as vaccines. The vaccine is manufactured by Merck Sharp & Dohme B.V. and is authorized for use in the European Union under the marketing authorization number EU/1/15/1007/001. The pharmaceutical form of the vaccine is a suspension for injection, and it is administered via the **intramuscular route**.

The dosing regimen for Gardasil 9 in this trial involves a maximum daily dose of 0.5 ml per administration, with a total maximum dose of 3 ml over the course of the treatment period. The maximum treatment period is set at 7 days. The trial aims to compare the immune response to the vaccine when administered at two different time points post-allogeneic stem cell transplantation: an early start at 9 months and a late start at 15 months. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the efficacy and safety of the Gardasil 9 vaccine in the specified patient population. The trial is designed to provide insights into the optimal timing of vaccination post-transplant to achieve the best possible immune response.

Efficacy in this clinical trial will be assessed by evaluating the immune response to the **Gardasil 9** vaccine in patients who have undergone allogeneic stem cell transplantation. The primary endpoint is the geometric mean titer (GMT) of antibodies against **HPV 16**, measured one month after the administration of the third vaccine dose, comparing early (9 months post-transplant) versus late (15 months post-transplant) vaccination. Secondary endpoints include the GMT of antibodies against all nine HPV serotypes included in the vaccine, measured at one month and twelve months after the third vaccine dose. Additionally, the proportion of participants who are seropositive or seronegative for the nine HPV serotypes will be assessed at one and twelve months post-vaccination. Seroconversion rates will also be evaluated by comparing pre-vaccination antibody levels to those one month after the third dose. The proportion of participants seropositive for seven out of nine HPV types will be measured at one and twelve months following the completion of the vaccination series.