Does the HPV Vaccine Cause the Same Response in Adolescent Kidney and Liver Transplant Patients as in Healthy Controls?

Cervical Cancer Clinical Trial

Official title:

Immunogenicity Of A Prophylactic Quadrivalent Human Papillomavirus (Types 6, 11, 16, And 18) L1 Virus-Like Particle Vaccine In Male And Female Adolescent Transplant Recipients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01101750
• Other study ID #: GardasilMerckGomez-Lobo
• Status: Completed
• Phase: Phase 4
• Start date: May 2010
• Est. completion date: December 14, 2012

Study information

• Verified date: December 2020
• Source: Medstar Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to understand if children with liver and kidney transplants develop the antibodies from the Gardasil vaccine.

The Gardasil vaccine protects against Human Papilloma Virus (HPV) types 16 and 18, which cause most types of cancers of the cervix, vagina and vulva. It also protects against Human Papilloma Virus types 6 and 11, which cause genital warts in some people. Gardasil has been approved by the Food and Drug Administration and is recommended for girls and women from ages 9-26 for the prevention of some types of cancer of the cervix, vagina and vulva as well as preventing some types of genital warts. In males that are 9-26 years old, the FDA has approved its use for prevention of some types of genital warts.

The Gardasil vaccine is made from a virus like particle and does not contain any live virus. Children with an allergy to yeast should not receive the vaccine since some components of the vaccine are made from yeast.

People who have undergone organ transplant are at increased risk of of developing genital warts and cancers related to HPV when compared to the general population. The American Society of Transplantation and the American Society of Transplant Surgeons recommend the vaccine for people with transplants.

Studies of other vaccines like Hepatitis B have shown children after transplant have less of a response to this vaccine and are not immune to the Hepatitis B virus. We are interested in seeing if your child will form antibodies (immune response) to the Gardasil vaccine.

Your child is being asked to be in the study because he or she is between the ages of 9-17 and has undergone a liver or kidney transplant more than 6 months ago and does not have any signs of organ rejection.

Description:

Currently Merck manufactures the HPV (types 6, 11, 16, and 18) L1 virus like particle vaccine and a description has been reported previously. (18) Merck will supply the vaccine, which will be stored as directed by the manufacturer. The vaccine will be stored at the Medstar Research Institute (Women and Infants Research Services) It will be administered by intramuscular injection (0.5 mL) into the upper arm or thigh by the research nurse (Sarah Duwel, RN or a nurse working under supervision) in the transplant clinic.

Participants will be given a form to fill out regarding allergic prior to vaccination. After the research nurse reviews the form with the patient and their guardian, an immunization or blood collection will be performed. Participants will receive a full dose vaccine on day 1, at month 2 (± 3 weeks), and at month 6 (± 3 weeks). All participants will be required to be afebrile (oral temperature <37.8° C) within 24 hours before each injection.

All female participants will undergo urine pregnancy testing and will not be vaccinated if found to be pregnant. Female participants with a positive urine pregnancy test will be informed confidentially of their test results by the study nurse and will be referred to an OB/GYN for further care.

Serum samples will be obtained from all participants on day 1, at month 3, and at month 7. Samples will be de-identified and stored at -20°C or below and anti-HPV levels will be determined using an HPV type-specific competitive Luminex xMAP-based immunoassay (cLIA). (18) Merck will make arrangements for the labs tests. This assay measures only neutralizing anti-HPV antibodies, rather than the broad assortment of vaccine-induced anti-HPV antibodies. Antibody levels will be expressed as milliMerck units (mMU) per milliliter. The lower limits of detection for the anti-HPV 6, 11, 16, and 18 cLIAs are 4.1 mMU6/mL, 3.0 mMU11/mL, 10.2 mMU16/mL, and 2.9 mMU18/mL, respectively. Assay precision is estimated to be 21.7%, 20.4%, 23.0%, and 15.9% for the anti-HPV 6, 11, 16, and 18 cLIAs respectively. Participants will be considered anti-HPV 6, 11, 16, or 18 seropositive when their anti-HPV antibody titers are 20 mMU6/mL, 16 mMU11/mL, 20 mMU16/mL, or 24 mMU18/mL, respectively.

Blood collection supplies will be obtained from a lab vendor Laprepco (www.labrepco.com). The lab we will use to process our antibody titers is PPD Labs (www.ppdi.com). De-identified blood samples will be stored by the research nurse at Mesdstar Research Institute until they are able to be shipped to the PPD lab. Our research nurses are trained in Environmental and Health Safety training based on Medstar Research Institution requirements. Antibody titers results will be mail directly to Dr. Gomez-Lobo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 14, 2012
• Est. primary completion date: January 20, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 9 Years to 17 Years

Eligibility

Inclusion Criteria:

• Male and female patients age 9-17 who have undergone liver or kidney transplant are on stable immunosuppressant doses for greater than 6 months

Exclusion Criteria:

• Previous vaccination with Gardasil or Cervarix

• Allergy to Gardasil or components of Gardasil including yeast

• Diagnosis of HIV or cancer

• Pregnancy

• Blood transfusion 6 months prior to initiation of Gardasil vaccine protocol

Related Conditions & MeSH terms

• Cervical Cancer
• Hpv
• Uterine Cervical Neoplasms
• Warts

Intervention

Biological:
• Quadrivalent HPV for types 6, 11, 16 and 18
Per standard of care, Gardasil 0.5ml IM injection on day one, month 2, and month 6. Serum samples on day one, month 3 and month 7.

Locations

Country	Name	City	State
United States	Childrens National Medical Center	Washington	District of Columbia
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Medstar Health Research Institute	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (17)

Badawi H, Ahmed H, Ismail A, Diab M, Moubarak M, Badawy A, Saber M. Role of human papillomavirus types 16, 18, and 52 in recurrent cystitis and urinary bladder cancer among Egyptian patients. Medscape J Med. 2008;10(10):232. Epub 2008 Oct 8. — View Citation

Block SL, Nolan T, Sattler C, Barr E, Giacoletti KE, Marchant CD, Castellsagué X, Rusche SA, Lukac S, Bryan JT, Cavanaugh PF Jr, Reisinger KS; Protocol 016 Study Group. Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics. 2006 Nov;118(5):2135-45. — View Citation

Carey W, Pimentel R, Westveer MK, Vogt D, Broughan T. Failure of hepatitis B immunization in liver transplant recipients: results of a prospective trial. Am J Gastroenterol. 1990 Dec;85(12):1590-2. — View Citation

D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56. — View Citation

Danzinger-Isakov L, Kumar D; AST Infectious Diseases Community of Practice. Guidelines for vaccination of solid organ transplant candidates and recipients. Am J Transplant. 2009 Dec;9 Suppl 4:S258-62. doi: 10.1111/j.1600-6143.2009.02917.x. — View Citation

De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer. 2009 Apr 1;124(7):1626-36. doi: 10.1002/ijc.24116. — View Citation

Duca P, Del Pont JM, D'Agostino D. Successful immune response to a recombinant hepatitis B vaccine in children after liver transplantation. J Pediatr Gastroenterol Nutr. 2001 Feb;32(2):168-70. — View Citation

FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27. — View Citation

Guidelines for vaccination of solid organ transplant candidates and recipients. Am J Transplant. 2004 Nov;4 Suppl 10:160-3. Review. — View Citation

Joura EA, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, García P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch X, Dillner J, Kurman RJ, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, Lu S, Vuocolo S, Hesley TM, Haupt RM, Barr E. HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine. Vaccine. 2008 Dec 9;26(52):6844-51. doi: 10.1016/j.vaccine.2008.09.073. Epub 2008 Oct 16. — View Citation

Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant. 2004 Jun;4(6):905-13. — View Citation

Lefebure AF, Verpooten GA, Couttenye MM, De Broe ME. Immunogenicity of a recombinant DNA hepatitis B vaccine in renal transplant patients. Vaccine. 1993;11(4):397-9. — View Citation

Loinaz C, de Juanes JR, Gonzalez EM, López A, Lumbreras C, Gómez R, Gonzalez-Pinto I, Jiménez C, Garcia I, Fuertes A. Hepatitis B vaccination results in 140 liver transplant recipients. Hepatogastroenterology. 1997 Jan-Feb;44(13):235-8. — View Citation

Penn I. Occurrence of cancers in immunosuppressed organ transplant recipients. Clin Transpl. 1998:147-58. — View Citation

Rendi-Wagner P, Kundi M, Stemberger H, Wiedermann G, Holzmann H, Hofer M, Wiesinger K, Kollaritsch H. Antibody-response to three recombinant hepatitis B vaccines: comparative evaluation of multicenter travel-clinic based experience. Vaccine. 2001 Feb 28;19(15-16):2055-60. — View Citation

Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen OE, Olsson SE, Høye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, Krogh Gv, Lehtinen M, Malm C, Tamms GM, Giacoletti K, Lupinacci L, Railkar R, Taddeo FJ, Bryan J, Esser MT, Sings HL, Saah AJ, Barr E. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006 Dec 4;95(11):1459-66. Epub 2006 Nov 21. — View Citation

Villa LL. Overview of the clinical development and results of a quadrivalent HPV (types 6, 11, 16, 18) vaccine. Int J Infect Dis. 2007 Nov;11 Suppl 2:S17-25. doi: 10.1016/S1201-9712(07)60017-4. Review. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects Showing Seroconversion to All HPV Four Serotypes		7 months