Clinical trial NCT03629886: Safety and Protective Effect Study of GSK Biologicals' Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed (GSK580299) in Healthy Female Subjects From the HPV-039 Study
Official title: Safety and Protective Effect Study of GSK Biologicals' Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed (GSK580299) in Healthy Female Subjects From the HPV-039 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cervical Intraepithelial Neoplasia
Keywords: Adults
Human Papillomavirus (HPV)
Cervical cancer
Safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2018-08-14
Enrollment: 6051
Sex: FEMALE
Minimum age (years): 26
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study was designed to enable all subjects who received placebo in the HPV-039 study (NCT00779766), to also receive GSK Biologicals' Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed. Safety data in terms of serious adverse events (SAEs), any adverse events (AEs)/SAEs leading to premature discontinuation of the study, potential immune mediated diseases (pIMDs) and pregnancies (and their outcomes) were collected during the study period.

In addition, this study assessed the long term protective effect of the vaccine, in an exploratory manner, in terms of rates of HPV-related (vaccine type) incident cervical infection up to approximately 10 years after vaccination in subjects who participated in HPV-039 study (NCT00779766).

Detailed description: Treatment allocation depended on the randomization in the previous study i.e. only the subjects from the control group of HPV-039 study received HPV vaccination in the current study. Subjects who previously received the Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed in HPV-039 study did not receive vaccination in this study.

Eligibility criteria: Inclusion Criteria:

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Written informed consent obtained from the subject prior to performing any study specific procedure.
* Subjects previously enrolled in the HPV-039 study.
* Subjects with negative pregnancy test at Visit 1.

Additional inclusion criteria for subjects of HPV group undergoing vaccination ONLY:

* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Female subjects of non-childbearing potential may be enrolled in the study.

  * Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
* Previous vaccination against HPV outside of study HPV-039.

Additional exclusion criteria for subjects of HPV group undergoing vaccination ONLY:

* Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine, or planned use during the study period.
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone. Inhaled and topical steroids are allowed.
* Planned administration/administration of a vaccine/product not foreseen by the study protocol in the period starting 30 days before and after each dose of vaccine administration, with the exception of administration of routine vaccines e.g. meningococcal, hepatitis B, hepatitis A, inactivated influenza up to eight days before and after each dose of study vaccine. Enrolment will be deferred until the subject is outside of the specified window.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
* Previous administration of MPL or AS04 adjuvant.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
* Cancer or autoimmune disease under treatment.
* Hypersensitivity to latex.
* Acute disease and/or fever at the time of enrolment.

  * Fever is defined as temperature ≥37.0°C. The preferred location for measuring temperature in this study will be the axilla.
  * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
* Pregnant or breastfeeding. Subjects must be at least three months post-pregnancy and not breastfeeding to enter the study.
* Females planning to become pregnant or planning to discontinue contraceptive precautions during the vaccination phase of the study, i.e. up to two months after the last vaccine dose.

Primary outcomes:
measure: Number of Subjects With Serious Adverse Events (SAEs) Related to Study Vaccine in Vacc-092 Group
timeFrame: During the entire study period (Day 1-Month 12)
Secondary outcomes:
measure: Number of Subjects With Potential Immune Mediated Diseases (pIMDs) in Vacc-092 Group
timeFrame: During the entire study period (Day 1-Month 12)
measure: Number of Pregnant Subjects Reported With Outcomes of Pregnancy in Vacc-092 Group
timeFrame: During the entire study period (Day 1-Month 12)
measure: Number of Subjects With SAEs in Vacc-092 Group
timeFrame: During the entire study period (Day 1-Month 12)
measure: Number of Subjects With Any Adverse Events or Serious Adverse Events (AE/SAE) Leading to Premature Discontinuation From the Study in Vacc-092 Group
timeFrame: During the entire study period (Day 1-Month 12)
measure: Number of Subjects With SAEs Related to Study Participation in All Study Groups
timeFrame: During the entire study period (Day 1-Month 12)
measure: Incidence Rates of Incident Cervical Infection With HPV-16 and/or HPV-18 (by PCR) in HPV DNA Negative and Seronegative Subjects at Baseline in All Study Groups
timeFrame: From Month 0 in HPV-039 (NCT00779766) study [at the Day after Dose 1 (out of 3 doses administered in HPV-039)] until Month 120 (corresponding to Day 1 in the current study)
measure: Incidence Rates of Incident Cervical Infection With HPV-16 and/or HPV-18 (by PCR) in HPV DNA Negative Subjects at Baseline, Regardless of Initial Serostatus in All Study Groups
timeFrame: From Month 0 in HPV-039 (NCT00779766) study [at the Day after Dose 1 (out of 3 doses administered in HPV-039)] until Month 120 (corresponding to Day 1 in the current study)
measure: Incidence Rates of Incident Cervical Infection With Any Oncogenic HPV Type or Combination of Oncogenic HPV Types in HPV DNA Negative Subjects at Baseline, Regardless of Initial Serostatus in All Study Groups
timeFrame: From Month 0 in HPV-039 (NCT00779766) study [at the Day after Dose 1 (out of 3 doses administered in HPV-039)] until Month 120 (corresponding to Day 1 in the current study)
Other outcomes:
Locations:
city: Jintan
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Lianshui
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Xuzhou
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Yancheng
country: China
facility: GSK Investigational Site
state: Jiangsu
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Zhao F, Jastorff A, Hong Y, Hu S, Chen W, Xu X, Zhu Y, Zhu J, Zhang X, Zhang W, Xu D, Wang D, Tang R, Sun Y, Shen Y, Pan Q, Yin J, Liu D, Liu B, Karkada N, Jiang C, Cui J, Chen F, Bi J, Bao Y, Zhou X, Cartier C, Hu Y, Borys D. Safety of AS04-HPV-16/18 vaccine in Chinese women aged 26 years and older and long-term protective effect in women vaccinated at age 18-25 years: A 10-year follow-up study. Asia Pac J Clin Oncol. 2023 Aug;19(4):458-467. doi: 10.1111/ajco.13833. Epub 2022 Sep 13.