Safety and Immunogenicity Study of MEDI-517 (GSK 580299) With or Without Adjuvant in Healthy Adult Females

Study Overview
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Brief Summary
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The goals of this study are to describe the safety, reactogenicity and immunogenicity of MEDI-517 with and without adjuvant in HPV-naïve humans. Long-term immune data is collected. This study was originally performed by MedImmune. However, GSK is now responsible for the clinical development of the HPV vaccine.

Detailed Description
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This is a Phase II, double-blind, randomized, comparative trial of three formulations of MEDI-517 given at 0, 30, and 180 days by intramuscular injection. The volunteers in this study will be healthy females 18 through 30 years of age. The study collects safety, reactogenicity and immunogenicity data of MEDI-517 with and without adjuvant. Extended follow-up will provide long-term immune response data.

Official Title
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Study to Evaluate the Safety and Immunogenicity of MEDI-517, a Virus-Like Particle Vaccine Against Human Papillomavirus Types 16 and 18, When Formulated With Aluminum Hydroxide, AS04, or Without Adjuvant, in Healthy Adult Female Volunteers

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Biological: MEDI-517 HPV-16/18 VLP AS04 vaccine
* Biological: MEDI-517 HPV-16/18 VLP vaccine with Al(OH)3
* Biological: MEDI-517 HPV-16/18 VLP vaccine without adjuvant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females 18 through 30 years of age (must not have reached the 31st birthday) Written informed consent obtained from the volunteer Unless previously surgically sterilized, agrees to use an effective method of birth control beginning 30 days before the first study injection and continuing through 60 days after the final study injection Must have a negative serum pregnancy test within 21 days of study entry and must not be breast feeding Healthy by medical history and physical examination Seronegative for HPV-16 and HPV-18 antibody by ELISA within 21 days of study entry Cervical specimen negative for high-risk HPV DNA using the Digene Hybrid Capture® II HPV test (high-risk types Probe B) within 21 days of study entry Normal Pap smear, using the Cytyc ThinPrep® Pap Test, within 21 days of study entry No evidence of anogenital HPV lesions or physical findings suggestive of other gynaecologic pathogens on pelvic examination within 21 days of study entry Agrees to no other vaccines or experimental therapy until 30 days after the last study injection Exclusion Criteria: Acute illness or fever (oral temperature ≥ 99.5°F [37.5°C]) at start of the study History or clinical manifestations of significant medical or psychiatric disorder Use of immunosuppressive medication (inhaled and topical corticosteroids are permitted) within the previous 90 days or history of immunodeficiency History of cancer History of alcohol or drug abuse within the past 2 years Abnormal laboratory blood values at screening. Other abnormal laboratory values in the screening panel which in the opinion of the principal investigator are judged to be clinically significant Receipt of immunoglobulin or blood products within 90 days prior to study entry History of abnormal Pap smear (other than a single prior report of ASCUS or indeterminate Pap smear with a subsequent normal report) Genital herpes disease involving the cervix or with disease characterized on examination or by history by extensive external lesions. Volunteers with a history of recurrent genital herpes disease characterized by limited external lesions are eligible to participate in the study. Positive tests for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 antibody Any prior receipt of any vaccine (experimental or otherwise) for treatment or prophylaxis of genital warts or other papillomavirus related condition. Any treatment of genital warts or other papillomavirus related condition within 6 months of randomization (local therapy for common skin and/or plantar warts is allowed) Previous administration of any components of the investigational vaccine Receipt of any experimental vaccine within 90 days prior to entry into this study Receipt of any experimental drug therapy within 30 days or five half-lives of the experimental drug (if the half-life is known), whichever is longer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Formulation 1 of the vaccine (MEDI-517 HPV-16/18 VLP AS04 vaccine) | Biological: MEDI-517 HPV-16/18 VLP AS04 vaccine<br>* IM injection<br>|
| Experimental: Group B<br>Formulation 2 of the vaccine [with Al(OH)3] | Biological: MEDI-517 HPV-16/18 VLP vaccine with Al(OH)3<br>* IM injection<br>|
| Experimental: Group C<br>Formulation 3 of the vaccine (without adjuvant) | Biological: MEDI-517 HPV-16/18 VLP vaccine without adjuvant<br>* IM injection<br>* Other names: MEDI-517 HPV-16/18 VLP vaccine with Al(OH)3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited adverse event rates (including injection site and systemic reactions) |  | For 7 days after each injection | 
| Solicited adverse event rates |  | For 30 days after each injection | 
| Serious adverse event rates |  | From first injection through 6 months after last injection | 
| Laboratory assessments (Chemistry and Hematology parameters) |  | Study Days 0, 30 and 210 | 
| Vital signs (temperature, blood pressure, pulse rate, respiratory rate) |  | At the time of each injection and 30 minutes after each injection | 
| Serum ELISA titers against HPV-16 and HPV-18 |  | 30 days after the third injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum ELISA titers against HPV-16 and HPV-18 |  | Study Days 0, 7, 30, 60, 180, 210, and 360, and at 18, 24, 36, and 48 months | 
| Neutralization titers against HPV-16 and HPV-18 |  | Study Days 0, 60, 210 and 360 | 
| Inhibitory ELISAs |  | Study Days 0, 60, 210, and 360, and at 18, 24, 36, and 48 months | 
| Lymphoproliferative, IL-5, and IFN-γ assays |  | Study Days 0, 60, 210, and 360, and at 18, and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, Vaccine