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

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

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.

Study Overview

• Status: Completed
• Conditions: Infections, Papillomavirus
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Solicited adverse event rates (including injection site and systemic reactions)	For 7 days after each injection
Serum ELISA titers against HPV-16 and HPV-18	30 days after the third 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

Secondary Outcome Measures

Outcome Measure	Time Frame
Neutralization titers against HPV-16 and HPV-18	Study Days 0, 60, 210 and 360
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
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008 Dec 2;26(51):6630-8. doi: 10.1016/j.vaccine.2008.09.049.
• Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009 May;5(5):332-40. doi: 10.4161/hv.5.5.7211. Epub 2009 May 20.
• Giannini SL, Hanon E, Moris P, Van Mechelen M, Morel S, Dessy F, Fourneau MA, Colau B, Suzich J, Losonksy G, Martin MT, Dubin G, Wettendorff MA. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine. 2006 Aug 14;24(33-34):5937-49. doi: 10.1016/j.vaccine.2006.06.005. Epub 2006 Jun 19.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): January 1, 2005

Study Registration Dates

• First Submitted: June 5, 2008
• First Submitted That Met QC Criteria: June 5, 2008
• First Posted (Estimate): June 9, 2008

Study Record Updates

• Last Update Posted (Estimate): September 16, 2016
• Last Update Submitted That Met QC Criteria: September 15, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: HPV, Vaccine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 580299/004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: 580299/004
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 580299/004
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: 580299/004
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 580299/004
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 580299/004
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 580299/004
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 580299/004
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register