HPV Vaccine for Low Lymphocyte Count

Overseen By Andrea Lisco, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Glucocorticosteroids, Immunomodulants

Disqualifiers: HIV, Cancer, Autoimmune, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

54 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Diseases related to human papillomavirus (HPV) include warts, lesions, and cancers. ICL is idiopathic CD4 T cell lymphocytopenia. People with this rare disease get more HPV-related diseases than other people do. The diseases are more severe and harder to treat in people with ICL. Researchers want to see if the vaccine GARDASIL 9 can help people with ICL. Objective: To study the effects of the vaccine GARDASIL 9 in people with ICL. Eligibility: Adults ages 18-65 with ICL Healthy volunteers the same age Design: Participants will be screened with a physical exam, medical history, and blood and pregnancy tests. Participants will have a baseline visit with: * Physical exam * Medical history * Oral rinse collection. Participants will gargle a small amount of a saline solution, then spit it into a cup. * Apheresis. Blood will be removed through a needle in an arm. A machine will separate the blood and keep some parts for research. The rest will be returned to the participant through a needle in the other arm. * Examination for HPV-related disease. Female participants will have a Pap test. Researchers will collect swabs from some participants skin or genital lesions. Participants will get 3 doses of the study vaccine over 6 months as a shot in the upper arm or thigh muscle. They will repeat the screening tests each vaccine visit. Participants will record their temperature and side effects for several days after vaccinations. Participants may have visits after vaccinations. Participants will have 2 follow-up visits in the 18 months after the last vaccine. They will repeat most of the baseline tests. ...

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using systemic glucocorticosteroids or certain immunomodulants, you may not be eligible to participate.

What data supports the effectiveness of the HPV vaccine Gardasil 9 for treating low lymphocyte count?

Gardasil 9, an HPV vaccine, has shown high effectiveness in preventing infections and diseases caused by specific HPV types, such as cervical cancer and genital warts, in various studies. While there is no direct evidence for its use in treating low lymphocyte count, its proven ability to stimulate a strong immune response suggests potential benefits in immune-related conditions. ^{1 2 3 4 5}

Is the HPV vaccine, including Gardasil 9, generally safe for humans?

The HPV vaccine, including Gardasil 9, is generally considered safe for humans. In a study from Italy, only 22 adverse events were reported out of 266,647 doses, with a very low rate of serious events. Another study in Korea found no serious adverse events, with most reactions being mild and related to the injection site. ^{6 7 8 9 10}

How does the HPV vaccine Gardasil 9 differ from other treatments for low lymphocyte count?

Gardasil 9 is unique because it is primarily designed to prevent HPV infections and related cancers by inducing strong immune responses, rather than directly treating low lymphocyte count. It works by stimulating the body to produce antibodies against multiple HPV types, which is different from treatments that might directly target lymphocyte levels. ^{1 5 11 12 13}

Research Team

Andrea Lisco, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

Adults aged 18-70 with idiopathic CD4 T cell lymphocytopenia (ICL) or healthy volunteers meeting specific CD4 count criteria. Participants must not be pregnant, breastfeeding, have had GARDASIL 9 before, severe allergies to vaccine components, HIV, certain acute illnesses or immunodeficiencies, recent cancer treatments or immunomodulants.

Inclusion Criteria

I agree to use birth control if there's a chance I could get pregnant.

I started hormonal treatment at least a month before the first dose of the study drug.

Healthy volunteers must have CD4 cell count of greater than or equal to 450 cells/microL within 90 days prior to day 0.

Exclusion Criteria

Any condition that, in the opinion of the investigator, contraindicates participation in this study.

I have HIV or another type of immune system problem.

Receipt of ACIP recommended immunizations within 1 week of day 0.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Participants undergo baseline assessments including physical exam, medical history, and apheresis

1 day

1 visit (in-person)

Vaccination

Participants receive 3 doses of the GARDASIL 9 vaccine over 6 months

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and immunogenicity, with follow-up visits 1 and 18 months after the last vaccine dose

18 months

2 visits (in-person)

Treatment Details

Interventions

• Gardasil 9

Trial Overview The trial is testing the effectiveness of the HPV vaccine GARDASIL 9 in people with ICL compared to healthy individuals. It involves three doses over six months and follow-up visits for up to 18 months after the last dose to monitor immune response and side effects.

Participant Groups

Group I: ICL and Healthy Volunteers Experimental Treatment 1 Intervention

Biological/Vaccine

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Findings from Research

Both Gardasil and Cervarix HPV vaccines have shown outstanding efficacy in preventing infections and related conditions in young women, with excellent safety profiles and only mild to moderate side effects reported.

Neither vaccine is effective in treating existing HPV infections or lesions, but they provide strong protection against specific HPV types for at least four years, with Gardasil also preventing genital warts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Schiller, JT., Castellsagué, X., Villa, LL., et al.[2022]

All three HPV vaccines (bivalent, quadrivalent, and 9vHPV) show high efficacy in preventing infections from specific HPV types and associated high-grade cervical dysplasia in women who have not been previously exposed to HPV.

While the bivalent and quadrivalent vaccines have demonstrated early clinical effectiveness in reducing HPV 16 and 18 prevalence, the overall benefits of HPV vaccination in reducing cervical cancer are still largely theoretical, highlighting the need for large-scale studies to confirm long-term effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of 2-, 4- and 9-valent HPV vaccines on morbidity and mortality from cervical cancer. Luckett, R., Feldman, S.[2018]

In a study of 178 women under 45 years old with a history of HPV disease, those who received the quadrivalent HPV vaccine after treatment had a significantly lower recurrence rate of HPV-linked disease (3.4%) compared to those who did not receive the vaccine (13.5%).

The results indicate that HPV vaccination during follow-up can effectively reduce the risk of disease recurrence, suggesting that it should be considered as part of post-treatment management for women with HPV-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indication of prophylactic vaccines as a tool for secondary prevention in HPV-linked disease. Pieralli, A., Bianchi, C., Auzzi, N., et al.[2019]

The two-dose HPV vaccine series for pre-adolescent girls (ages 9-15) is effective in providing protection against HPV 16 and other types, with the World Health Organization recommending this schedule since 2015, while older women still require a three-dose series.

Gardasil9 and Cervarix both show strong efficacy in preventing HPV infections, with Cervarix offering a potentially more cost-effective option due to its sustained high antibody levels and the possibility of effective protection with just one dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HPV vaccines - A review of the first decade. Harper, DM., DeMars, LR.[2022]

In a study of 266,647 doses of Gardasil-9® administered in Puglia, Italy, only 22 adverse events following immunization (AEFIs) were reported, resulting in a low reporting rate of 8.25 per 100,000 doses, indicating a favorable safety profile for the vaccine.

Out of the 22 reported AEFIs, only 5 were classified as serious, with 2 leading to hospitalization; however, only 2 serious AEFIs were consistently associated with the vaccine, suggesting that the benefits of Gardasil-9® outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. Di Lorenzo, A., Berardi, P., Martinelli, A., et al.[2022]

In a study involving 12,066 women aged 9 to 26 years who received the HPV vaccines Gardasil® and Cervarix® over three years, 61% reported experiencing mild and transient adverse events after the first dose.

The high rate of reported adverse events is attributed to the study's design, which encouraged participants to document all occurrences, highlighting the importance of ongoing surveillance for vaccine safety, especially for newly marketed vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human papillomavirus vaccine register]. Spila-Alegiani, S., Da Cas, R., Giambi, C., et al.[2013]

The post-licensure safety profile of HPV vaccines Gardasil and Cervarix was evaluated using data from three sources, including VigiBase and VAERS, confirming that the reported adverse events align with existing safety data.

The analysis showed that the safety profiles of both vaccines are consistent with the information provided in their Summary of Product Characteristics (SPC), indicating that they are safe for public use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postlicensure safety evaluation of human papilloma virus vaccines. Labadie, J.[2015]

In a study of 316 females who reported suspected severe adverse reactions to the HPV vaccine, it was found that these individuals had significantly higher health care-seeking behavior in the two years prior to vaccination compared to a control group of over 163,000 individuals.

The cases showed increased consultations for various health issues, including psychological support and musculoskeletal problems, suggesting that pre-existing health conditions may influence perceptions of vaccine safety and should be considered when evaluating vaccine safety signals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-Vaccination Care-Seeking in Females Reporting Severe Adverse Reactions to HPV Vaccine. A Registry Based Case-Control Study. Mølbak, K., Hansen, ND., Valentiner-Branth, P.[2019]

The 9-valent HPV vaccine (Gardasil 9®) significantly increases protection against cervical cancer by covering 9 oncogenic HPV types, raising potential protection from about 70% to 90%, based on clinical trials involving young women.

Clinical trials demonstrated that the 9vHPV vaccine has a comparable safety profile and immunogenicity to the original 4-valent vaccine, with a 2-dose regimen showing similar effectiveness in younger boys and girls compared to the standard 3-dose regimen for older women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. Zhang, Z., Zhang, J., Xia, N., et al.[2019]

The nine-valent HPV vaccine, Gardasil9, significantly increases the efficacy against cervical cancer from 70% to 90% compared to the quadrivalent vaccine, covering a broader range of HPV types.

Gardasil9 also provides high efficacy (97%) against lesions associated with HPV types 31, 33, 45, 52, and 58, while maintaining similar effectiveness against HPV types 6, 11, 16, and 18 as the quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. Fait, T., Dvořák, V., Pilka, R.[2018]

The quadrivalent HPV vaccine (Gardasil) effectively stimulated HPV-specific immune responses in HIV-infected young adults undergoing antiretroviral therapy, showing significant increases in various T lymphocyte populations after three doses.

The immune response in HIV-infected individuals was comparable to that of healthy controls, suggesting that the vaccine is both safe and effective in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papilloma virus vaccination induces strong human papilloma virus specific cell-mediated immune responses in HIV-infected adolescents and young adults. Rainone, V., Giacomet, V., Penagini, F., et al.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Human Papillomavirus Vaccine Efficacy and Effectiveness against Cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Impact of 2-, 4- and 9-valent HPV vaccines on morbidity and mortality from cervical cancer. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Indication of prophylactic vaccines as a tool for secondary prevention in HPV-linked disease. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

HPV vaccines - A review of the first decade. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

[Human papillomavirus vaccine register]. [2013]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Postlicensure safety evaluation of human papilloma virus vaccines. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Post-marketing surveillance study of the safety of the HPV-16/18 vaccine in Korea (2017-2021). [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Pre-Vaccination Care-Seeking in Females Reporting Severe Adverse Reactions to HPV Vaccine. A Registry Based Case-Control Study. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. [2019]

12. Czech Republic pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Human papilloma virus vaccination induces strong human papilloma virus specific cell-mediated immune responses in HIV-infected adolescents and young adults. [2018]