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

GlaxoSmithKline1,080 enrolled

Overview

The main purpose of this study was to evaluate the safety and reactogenicity of GlaxoSmithKline Biologicals SA (GSK)'s investigational adjuvanted human papillomavirus (HPV) vaccine formulations.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,080

Conditions

Cervical Intraepithelial Neoplasia

Interventions

HPV9 High formulationBIOLOGICAL

3 doses of the high formulation of HPV9 investigational adjuvanted vaccine were administered intramuscularly at Day 1, Month 2 and Month 6.

HPV9 Medium formulationBIOLOGICAL

3 doses of the medium formulation of HPV9 investigational adjuvanted vaccine were administered intramuscularly at Day 1, Month 2 and Month 6.

HPV9 Low formulationBIOLOGICAL

3 doses of the low formulation of HPV9 investigational adjuvanted vaccine were administered intramuscularly at Day 1, Month 2 and Month 6.

Eligibility

Sex: FEMALEMin age: 16 YearsMax age: 26 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Healthy participants as established by medical history and clinical examination before entering into the study. 2. For Step 1 only: Female between and including 18 and 26 years of age at the time of the first study intervention administration. 3. For Step 2: Female between and including 16 and 26 years of age at the time of the first study intervention administration. 4. 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). 5. 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). 6. Female participant with no more than 4 lifetime sexual partners prior to enrollment. 7. 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: 1. Pregnant or lactating female. 2. Female planning to become pregnant or planning to discontinue contraceptive precautions. 3. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s). 4. History or current diagnosis of autoimmune disease. 5. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). 6. Hypersensitivity to latex. 7. Major congenital defects, as assessed by the investigator. 8. History of abnormal Papanicolaou test or abnormal cervical biopsy result. 9. History of external genital/vaginal warts. 10. History of positive HPV test. 11. Acute or chronic clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests 12. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. 13. Previous vaccination against HPV. 14. Previous exposure to monophosphoryl lipid A (MPL) or AS04 adjuvant. 15. 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. 16. 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. 17. Administration of long-acting immune-modifying drugs at any time during the study period. 18. Use of systemic cytotoxic agents within the previous 3 months prior to randomization into this study or at any time during the study period. 19. 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. 20. 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. 21. 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. 22. History of /current chronic alcohol consumption and/or drug abuse. 23. Any study personnel or their immediate dependents, family, or household members. 24. Child in care.

Locations (68)

Outcomes

Primary Outcomes

Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 1

Assessed solicited administration site events included pain, redness and swelling at injection site. Grade 3 pain = significant pain at rest, which prevented normal everyday activities. Grade 3 redness/swelling = redness/swelling with a surface diameter greater than (\>) 50 millimeters (mm).

Time frame: Within 7 days after vaccine Dose 1 (administered at Day 1)

Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 2

Time frame: Within 7 days after vaccine Dose 2 (administered at Month 2)

Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 3

Time frame: Within 7 days after vaccine Dose 3 (administered at Month 6)

Number of Participants Reporting Grade 3 Solicited Systemic Events After Vaccine Dose 1

Assessed solicited systemic events included fever, headache, myalgia, arthralgia and fatigue. Grade 3 fever = body temperature \>39.0 degrees Celsius (°C) or 102.2 Fahrenheit (°F). The preferred location for measuring temperature was the axilla. Grade 3 headache, myalgia, arthralgia and fatigue = symptoms that prevented normal, every day activities.

Time frame: Within 7 days after vaccine Dose 1 (administered at Day 1)

Number of Participants Reporting Grade 3 Solicited Systemic Events After Vaccine Dose 2

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

3 doses of the marketed HPV vaccine (Gardasil 9) were administered intramuscularly at Day 1, Month 2 and Month 6.

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

Wheat Ridge, Colorado, United States

GSK Investigational Site

Coral Gables, Florida, United States

GSK Investigational Site

Kissimmee, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

North Miami Beach, Florida, United States

GSK Investigational Site

Pompano Beach, Florida, United States

GSK Investigational Site

Sarasota, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

...and 58 more locations

Assessed solicited systemic events included fever, headache, myalgia, arthralgia and fatigue. Grade 3 fever = body temperature \>39.0°C or 102.2°F. The preferred location for measuring temperature was the axilla. Grade 3 headache, myalgia, arthralgia and fatigue = symptoms that prevented normal, every day activity.

Time frame: Within 7 days after vaccine Dose 2 (administered at Month 2)

Number of Participants Reporting Grade 3 Solicited Systemic Events After Vaccine Dose 3

Time frame: Within 7 days after vaccine Dose 3 (administered at Month 6)

Number of Participants Reporting Grade 3 Unsolicited Adverse Events (AEs) After Vaccine Dose 1

An unsolicited AE is defined as an AE that was not included in the list of solicited events 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. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Grade 3 unsolicited AEs = an AE which prevented normal, everyday activities.

Time frame: Within 28 days after vaccine Dose 1 (administered at Day 1)

Number of Participants Reporting Grade 3 Unsolicited AEs After Vaccine Dose 2

An unsolicited AE is defined as an AE that was not included in the list of solicited events using an eDiary and that was spontaneously communicated by a participant/participant's parent(s)/LAR(s) who has signed the informed consent. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Grade 3 unsolicited AEs = an AE which prevented normal, everyday activities.

Time frame: Within 28 days after vaccine Dose 2 (administered at Month 2)

Number of Participants Reporting Grade 3 Unsolicited AEs After Vaccine Dose 3

An unsolicited AE is defined as an AE that was not included in the list of solicited events using an eDiary and that was spontaneously communicated by a participant/ participant's parent(s)/LAR(s) who has signed the informed consent. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Grade 3 unsolicited AEs = an AE which prevented normal, everyday activities.

Time frame: Within 28 days after vaccine Dose 3 (administered at Month 6)

Number of Participants Reporting Serious Adverse Events (SAEs)

An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or in other situations that were considered serious per medical or scientific judgment.

Time frame: From first vaccination (Day 1) to study end (Month 12)

Number of Participants in Step 1 Subset With Clinically Relevant Biochemical Abnormalities

As pre-specified in the protocol, the assessed biochemical parameters were blood urea nitrogen (BUN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Assessment of intensity: Grading of the biochemical parameters was based on the institutional normal reference ranges and derived from the standard Food and Drug Administration (FDA) Toxicity Grading Scale. Changes compared to normal reference ranges were graded as follows: Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening. Unknown = parameter value missing for the specified parameter.

Time frame: At Day 7

Number of Participants in Step 1 Subset With Clinically Relevant Hematological Abnormalities

As pre-specified in the protocol, the assessed hematological parameters were hemoglobin, white blood cells (WBC) increase, WBC decrease, lymphocyte decrease, neutrophils decrease, eosinophils, and platelets decrease. Assessment of intensity: Grading of the biochemical parameters was based on the institutional normal reference ranges and derived from the standard FDA Toxicity Grading Scale. Changes compared to normal reference ranges were graded as follows: Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening; Unknown = parameter value missing for the specified parameter.

Time frame: At Day 7

Number of Participants in Step 1 Subset With Clinically Relevant Abnormalities in Hemoglobin Change From Baseline Levels

The number of participants with clinically relevant abnormalities in hemoglobin change from baseline levels is reported. Assessment of intensity: Grading of the biochemical parameters was based on the institutional normal reference ranges and derived from the standard FDA Toxicity Grading Scale. Changes compared to normal reference ranges were graded as follows: Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening; Unknown = parameter value missing for the specified parameter. Change from baseline = the difference between a participant's baseline (pre-intervention) parameter values and their follow-up (post-intervention) parameter values.

Time frame: At Day 7 compared to baseline (Day 1)

Anti-HPV Immunoglobulin G (IgG) Antibody Concentrations

Anti-HPV IgG antibody concentrations were determined by electrochemiluminescence (ECL) assay and expressed as geometric mean concentrations (GMCs) in arbitrary units per milliliter (AU/mL). The assessed antigens were: HPV 6, HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 45, HPV 52 and HPV 58 type antigens.

Time frame: At Month 7 (one month after vaccine Dose 3 administration)

Secondary Outcomes

Number of Participants Reporting Any Solicited Administration Site Events

Assessed solicited administration site events included pain, redness and swelling at injection site. Any = occurrence of the symptom regardless of intensity grade.

Time frame: Within 7 days after each vaccine dose (administered at Day 1, Month 2, and Month 6)

Number of Participants Reporting Any Solicited Systemic Events

Assessed solicited systemic events included fever (defined as body temperature \>=37.5°C/99.5°F), headache, myalgia, arthralgia and fatigue. The preferred location for measuring temperature was the axilla. Any = occurrence of the symptom regardless of intensity grade or relation to study vaccination.

Time frame: Within 7 days after each vaccine dose (administered at Day 1, Month 2, and Month 6)

Number of Participants Reporting Any Unsolicited AEs

An unsolicited AE is defined as an AE that was not included in the list of solicited events using an eDiary and that was spontaneously communicated by a participant/participant's parent(s)/LAR(s) who has signed the informed consent. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Any = occurrence of the symptom regardless of intensity grade or relation to study vaccination.

Time frame: Within 28 days after each vaccine dose (administered at Day 1, Month 2, and Month 6)

Number of Participants Reporting Potential Immune-mediated Diseases (pIMDs)

pIMDs are defined as a subset of AEs of special interest (AESIs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

Time frame: From first vaccination (Day 1) to study end (Month 12)

Number of Participants Reporting Pregnancies

The number of participants who experienced pregnancy while participating in this study is reported.

Time frame: From Day 1 of pregnancy to study end (Month 12)

Number of Participants With Outcomes of Reported Pregnancies

The participants with confirmed pregnancies were followed up to determine the outcomes of the reported pregnancies. Pregnancy outcomes were live infant, no apparent congenital anomaly; elective termination, no apparent congenital anomaly, and ectopic pregnancy.

Time frame: From Day 1 of pregnancy up to study end (Month 12)

Anti-HPV IgG Antibody Concentrations

Anti-HPV IgG antibody concentrations were determined by ECL assay and expressed as GMCs in AU/mL. The assessed antigens were: HPV 6, HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 45, HPV 52 and HPV 58 type antigens.

Time frame: At Day 1, Month 2, Month 3, Month 6, Month 7 (Month 7 data was also reported in primary outcome measure 14, as pre-specified in protocol) and Month 12

Number of Participants With Seroconversion for Anti-HPV IgG Antibodies

Seroconversion is defined as the appearance of antibodies \[i.e., concentration greater than or equal to (\>=) the lower limit of quantification (LLOQ) value\] in the serum of participants seronegative \[i.e, concentrations less than (\<) the LLOQ value\] before vaccination. The assessed antigens were: HPV 6, HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 45, HPV 52 and HPV 58 type antigens. The LLOQ values specific to each antigen are as follows: HPV 6 type: LLOQ = 5100 AU/mL; HPV 11 type: LLOQ = 2480 AU/mL; HPV 16 type: LLOQ = 404 AU/mL; HPV 18 type: LLOQ = 1234 AU/mL; HPV 31 type: LLOQ = 3849 AU/mL; HPV 33 type: LLOQ = 617 AU/mL; HPV 45 type: LLOQ = 4079 AU/mL; HPV 52 type: LLOQ = 2352 AU/mL and HPV 58 type: LLOQ = 660 AU/mL.

Time frame: At Month 2, Month 3, Month 6, Month 7 and Month 12

Anti-HPV Neutralizing Titers

Anti-HPV neutralizing titers were determined by pseudovirion-based neutralization (PBNA) assay and expressed as geometric mean titers (GMTs). The assessed antigens were: HPV 6, HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 45, HPV 52 and HPV 58 type antigens.

Time frame: At Day 1, Month 3 and Month 7

Anti-HPV Neutralizing Titers in a Subset of Participants

Anti-HPV neutralizing titers were determined by PBNA assay and expressed as GMTs. The assessed antigens were: HPV 6, HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 45, HPV 52 and HPV 58 type antigens.

Time frame: At Month 2

Number of Participants With Seroconversion for Anti-HPV Neutralizing Antibodies

Seroconversion is defined as the appearance of antibodies (i.e., titer \>=LLOQ value) in the serum of participants seronegative (i.e, titer \<LLOQ value) before vaccination. The assessed antigens were: HPV 6, HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 45, HPV 52 and HPV 58 type antigens. The LLOQ values specific to each antigen are as follows: HPV 6 type: LLOQ = 269 titers; HPV 11 type: LLOQ = 279 titers; HPV 16 type: LLOQ = 339 titers; HPV 18 type: LLOQ = 84 titers; HPV 31 type: LLOQ = 96 titers; HPV 33 type: LLOQ = 323 titers; HPV 45 type: LLOQ = 76 titers; HPV 52 type: LLOQ = 104 titers and HPV 58 type: LLOQ = 95 titers.

Time frame: At Month 3 and Month 7

Correlation Between Anti-HPV IgG Antibody Concentration and Anti-HPV Neutralizing Antibody Titers

The Pearson coefficient of correlation between anti-HPV IgG antibody concentration and anti-HPV neutralizing antibody titers was calculated for each study group and for each antigen. The Pearson correlation was computed by the log10-transformation of specific antibody concentrations.

Time frame: At Day 1, Month 2, Month 3 and Month 7