A Study on the Immune Response and Safety of an Adjuvanted Human Papillomavirus Vaccine When Given to Healthy Women 16 to 26 Years of Age

Study Overview
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Brief Summary
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The Main purpose of this study is to evaluate the safety and reactogenicity of GlaxoSmithKline Biologicals SA (GSK)'s investigational adjuvanted human papillomavirus (HPV) vaccine formulations.

Official Title
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A Phase 1/2 Randomized, Observer-blinded, Multi-country Study to Evaluate Safety and Immunogenicity of Investigational Adjuvanted Human Papillomavirus Vaccine in Females (16 to 26 Years of Age)

Conditions
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Cervical Intraepithelial Neoplasia

Intervention / Treatment
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* Biological: HPV9 High formulation
* Biological: HPV9 Medium formulation
* Biological: HPV9 Low formulation
* Biological: Gardasil 9


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants as established by medical history and clinical examination before entering into the study. For Step 1 only: Female between and including 18 and 26 years of age at the time of the first study intervention administration. For Step 2: Female between and including 16 and 26 years of age at the time of the first study intervention administration. Written informed consent obtained from the participant prior to performance of any study specific procedure (for participants below the legal age of consent as per local regulations, written informed consent must be obtained from the participant/participant's parent[s]/legally authorized representatives [LAR{s}] and, in addition, the participant should sign and personally date a written informed assent). Participants and/or participants' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the eDiary, return for follow-up visits). Female participant with no more than 4 lifetime sexual partners prior to enrollment. Female participants of non-childbearing potential may be enrolled in the study. Female participants of childbearing potential may be enrolled in the study if the participant: has practiced adequate highly effective contraception for at least 1 month prior to study intervention administration, and has a negative pregnancy test on the day of study intervention administration, and has agreed to continue adequate contraception during the entire intervention period and for 2 months after completion of the study intervention administration series. Exclusion Criteria: Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s). History or current diagnosis of autoimmune disease. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Hypersensitivity to latex. Major congenital defects, as assessed by the investigator. History of abnormal Papanicolaou test or abnormal cervical biopsy result. History of external genital/vaginal warts. History of positive HPV test. Acute or chronic clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. Previous vaccination against HPV. Previous exposure to monophosphoryl lipid A (MPL) or AS04 adjuvant. Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use during the study period. Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before each dose and ending 30 days after each dose of study interventions administration* *In case emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is organized by public health authorities outside the routine immunization program, the time period described above can be reduced if, necessary for that vaccine, provided it is licensed and used according to its Product Information. Administration of long-acting immune-modifying drugs at any time during the study period. Use of systemic cytotoxic agents within the previous 3 months prior to randomization into this study or at any time during the study period. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first study intervention dose(s). For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants/ ≥0.5 milligram/kilogram/day (mg/kg/day) with maximum of 20 mg/day for participants under 18 years of age. Inhaled and topical steroids are allowed. Administration of systemic immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the administration of the first dose of study interventions or planned administration during the study period. Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non investigational intervention. History of /current chronic alcohol consumption and/or drug abuse. Any study personnel or their immediate dependents, family, or household members. Child in care.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 26 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: Human Papilloma Virus 9-valent (HPV9) High Group<br>Healthy females aged 16 to 26 years receive 3 doses of the HPV9-High formulation of the investigational adjuvanted HPV vaccine on Day 1, Month 2, and Month 6. | Biological: HPV9 High formulation<br>* 3 doses of a high formulation investigational adjuvanted HPV9 vaccine intramuscularly (IM) on Day 1, Month 2, and Month 6.<br>* Other names: Click here to enter text.;|
| Experimental: Human Papilloma Virus 9-valent (HPV9) Med Group<br>Healthy females aged 16 to 26 years receive 3 doses of the HPV9-Medium formulation of the investigational adjuvanted HPV vaccine on Day 1, Month 2, and Month 6. | Biological: HPV9 Medium formulation<br>* 3 doses of a medium formulation investigational adjuvanted HPV9 vaccine administered IM on Day 1, Month 2, and Month 6.<br>|
| Experimental: Human Papilloma Virus 9-valent (HPV9) Low Group<br>Healthy females aged 16 to 26 years receive 3 doses of the HPV9-Low formulation of the investigational adjuvanted HPV vaccine on Day 1, Month 2, and Month 6. | Biological: HPV9 Low formulation<br>* 3 doses of a low formulation investigational adjuvanted HPV9 vaccine administered IM on Day 1, Month 2, and Month 6.<br>|
| Active Comparator: Gardasil 9 (Gar9) Group<br>Healthy females aged 16 to 26 years receive 3 doses of the marketed HPV vaccine on Day 1, Month 2, and Month 6. | Biological: Gardasil 9<br>* 3 doses of the marketed HPV vaccine (Gradasil 9) administered IM on Day 1, Month 2, and Month 6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with Grade 3 solicited administration site events after dose 1 | Solicited administration site events include pain, redness, and swelling. Grade 3 pain is defined as significant pain at rest which prevents normal everyday activity. Grade 3 redness and swelling are defined as the greatest surface diameter in millimeters (mm) which is more than (>) 50 mm. | Within 7 days after the first study intervention dose (administered at Day 1) | 
| Percentage of participants with Grade 3 solicited administration site events after dose 2 | Solicited administration site events include pain, redness, and swelling. Grade 3 pain is defined as significant pain at rest which prevents normal everyday activity. Grade 3 redness and swelling are defined as the greatest surface diameter in (mm) which is >50 mm. | Within 7 days after the second study intervention dose (administered at Month 2) | 
| Percentage of participants with Grade 3 solicited administration site events after dose 3 | Solicited administration site events include pain, redness, and swelling. Grade 3 pain is defined as significant pain at rest which prevents normal everyday activity. Grade 3 redness and swelling are defined as the greatest surface diameter in mm which is >50 mm. | Within 7 days after the third study intervention dose (administered at Month 6) | 
| Percentage of participants with Grade 3 solicited systemic events after dose 1 | Solicited systemic events include fever, headache, fatigue, myalgia, and arthralgia. Grade 3 fever is defined as temperature >39.0 degrees Celsius (°C) or 102.2 Fahrenheit (°F). Grade 3 headache, fatigue, myalgia and arthralgia are defined as severe events that prevent normal activity. | Within 7 days after the first study intervention dose (administered at Day 1) | 
| Percentage of participants with Grade 3 solicited systemic events after dose 2 | Solicited systemic events include fever, headache, fatigue, myalgia, and arthralgia. Grade 3 fever is defined as temperature >39.0°C or 102.2°F. Grade 3 headache, fatigue, myalgia and arthralgia are defined as severe events that prevent normal activity. | Within 7 days after the second study intervention dose (administered at Month 2) | 
| Percentage of participants with Grade 3 solicited systemic events after dose 3 | Solicited systemic events include fever, headache, fatigue, myalgia, and arthralgia. Grade 3 fever is defined as temperature >39.0°C or 102.2°F. Grade 3 headache, fatigue, myalgia and arthralgia are defined as severe events that prevent normal activity. | Within 7 days after the third study intervention dose (administered at Month 6) | 
| Percentage of participants with Grade 3 unsolicited adverse events (AEs) after dose 1 | An unsolicited AE is an AE that was not included in the list of solicited using an eDiary and that was spontaneously communicated by a participant/ participant's parent(s)/ Legally acceptable representative(s) (LAR(s)) who has signed the informed consent. Grade 3 unsolicited AEs is an AE which prevents normal, everyday activity. | Within 28 days after the first study intervention dose (administered at Day 1) | 
| Percentage of participants with Grade 3 unsolicited AEs after dose 2 | An unsolicited AE is an AE that was not included in the list of solicited using an eDiary and that was spontaneously communicated by a participant/ participant's parent(s)/ LAR(s) who has signed the informed consent. Grade 3 unsolicited AEs is an AE which prevents normal, everyday activity. | Within 28 days after the second study intervention dose (administered at Month 2) | 
| Percentage of participants with Grade 3 unsolicited AEs after dose 3 | An unsolicited AE is an AE that was not included in the list of solicited using an eDiary and that was spontaneously communicated by a participant/participant's parent(s)/LAR(s) who has signed the informed consent. Grade 3 unsolicited AEs is an AE which prevents normal, everyday activity. | Within 28 days after the third study intervention dose (administered at Month 6) | 
| Percentage of participants with any serious adverse events (SAEs) | A SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, abnormal pregnancy outcomes, or other situations judged by the investigator as fitting the definition of a SAE. | From Day 1 up to end of study (Month 12) | 
| Percentage of participants with clinically relevant biochemical and hematological abnormalities | Clinically relevant abnormalities for each biochemical and hematological parameter are defined as parameters outside the defined normal ranges for each parameter and are assessed after the first vaccine dose administered. | At Day 7 | 
| Anti-HPV immunoglobulin G (IgG) antibody concentrations |  | At Month 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with solicited administration site events | Solicited administration site events include pain, redness, and swelling. | From Day 1 to Day 7 after administration of each vaccine dose (administered at Day 1, Month 2, and Month 6) | 
| Percentage of participants with solicited systemic events | Solicited systemic events include fever, headache, myalgia, arthralgia, and fatigue. | From Day 1 to Day 7 after administration of each vaccine dose (administered at Day 1, Month 2, and Month 6) | 
| Percentage of participants with unsolicited AEs | An unsolicited AE is an AE that was not included in the list of solicited using an eDiary and that was spontaneously communicated by a participant/participant's parent(s)/LAR(s) who has signed the informed consent. | From Day 1 to Day 28 after administration of each vaccine dose (administered at Day 1, Month 2, and Month 6) | 
| Percentage of participants with potential immune-mediated diseases (pIMDs) | pIMDs include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. | From Day 1 up to the end of study (Month 12) | 
| Percentage of participants experiencing pregnancy and pregnancy related outcomes |  | From Day 1 of pregnancy up to the end of study (Month 12) | 
| Anti-HPV immunoglobulin G (IgG) antibody concentrations |  | At Day 1, Month 2, Month 3, Month 6, Month 7, and Month 12 | 
| Number of seroconverted participants for anti-HPV IgG antibodies | Seroconversion is defined as the appearance of antibodies (i.e., concentrations greater than or equal to the cut-off value) in the serum of participants seronegative before vaccination. | At Day 1, Month 2, Month 3, Month 6, Month 7 and Month 12 | 
| Anti-HPV neutralizing antibody titers |  | At Day 1, Month 2, Month 3 and Month 7 | 
| Number of seroconverted participants with anti-HPV neutralizing antibodies | Seroconversion is defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of participants seronegative before vaccination. | At Month 3 and Month 7 | 
| Correlation between anti-HPV IgG antibody concentration and anti-HPV neutralizing antibody titers | Pearson coefficient is calculated for correlation between anti-HPV IgG antibody concentration and anti-HPV neutralizing antibody titers. | At Day 1, Month 2, Month 3 and Month 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human papillomavirus, infection, vaccine, women's health