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)
Overview
- Phase
- Phase 1
- Intervention
- HPV9 High formulation
- Conditions
- Cervical Intraepithelial Neoplasia
- Sponsor
- GlaxoSmithKline
- Enrollment
- 1080
- Locations
- 1
- Primary Endpoint
- Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 1
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
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.
Arms & Interventions
HPV9 High Group
Participants received 3 doses of the high formulation of Human Papilloma Virus 9-valent (HPV9) investigational adjuvanted vaccine at Day 1, Month 2, and Month 6.
Intervention: HPV9 High formulation
HPV9 Med Group
Participants received 3 doses of the medium formulation of Human Papilloma Virus 9-valent (HPV9) investigational adjuvanted vaccine at Day 1, Month 2, and Month 6.
Intervention: HPV9 Medium formulation
HPV9 Low Group
Participants received 3 doses of the low formulation of Human Papilloma Virus 9-valent (HPV9) investigational adjuvanted vaccine at Day 1, Month 2, and Month 6.
Intervention: HPV9 Low formulation
Gar9 Group
Participants received 3 doses of the marketed Human Papilloma Virus (HPV) vaccine (Gardasil 9) at Day 1, Month 2, and Month 6.
Intervention: Gardasil 9
Outcomes
Primary Outcomes
Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 1
Time Frame: Within 7 days after vaccine Dose 1 (administered at Day 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).
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)
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 \>50 mm.
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)
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 \>50 mm.
Number of Participants Reporting Grade 3 Solicited Systemic Events After Vaccine Dose 1
Time Frame: Within 7 days after vaccine Dose 1 (administered at Day 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.
Number of Participants Reporting Grade 3 Solicited Systemic Events After Vaccine Dose 2
Time Frame: Within 7 days after vaccine Dose 2 (administered at Month 2)
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.
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)
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.
Number of Participants Reporting Grade 3 Unsolicited Adverse Events (AEs) After Vaccine Dose 1
Time Frame: Within 28 days after vaccine Dose 1 (administered at Day 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.
Number of Participants Reporting Grade 3 Unsolicited AEs After Vaccine Dose 2
Time Frame: Within 28 days after vaccine Dose 2 (administered at Month 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.
Number of Participants Reporting Grade 3 Unsolicited AEs After Vaccine Dose 3
Time Frame: Within 28 days after vaccine Dose 3 (administered at Month 6)
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.
Number of Participants Reporting Serious Adverse Events (SAEs)
Time Frame: From first vaccination (Day 1) to study end (Month 12)
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.
Number of Participants in Step 1 Subset With Clinically Relevant Biochemical Abnormalities
Time Frame: At Day 7
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.
Number of Participants in Step 1 Subset With Clinically Relevant Hematological Abnormalities
Time Frame: At Day 7
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.
Number of Participants in Step 1 Subset With Clinically Relevant Abnormalities in Hemoglobin Change From Baseline Levels
Time Frame: At Day 7 compared to baseline (Day 1)
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.
Anti-HPV Immunoglobulin G (IgG) Antibody Concentrations
Time Frame: At Month 7 (one month after vaccine Dose 3 administration)
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.
Secondary Outcomes
- Number of Participants Reporting Any Solicited Administration Site Events(Within 7 days after each vaccine dose (administered at Day 1, Month 2, and Month 6))
- Number of Participants Reporting Any Solicited Systemic Events(Within 7 days after each vaccine dose (administered at Day 1, Month 2, and Month 6))
- Number of Participants Reporting Any Unsolicited AEs(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)(From first vaccination (Day 1) to study end (Month 12))
- Number of Participants Reporting Pregnancies(From Day 1 of pregnancy to study end (Month 12))
- Number of Participants With Outcomes of Reported Pregnancies(From Day 1 of pregnancy up to study end (Month 12))
- Anti-HPV IgG Antibody Concentrations(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(At Month 2, Month 3, Month 6, Month 7 and Month 12)
- Anti-HPV Neutralizing Titers(At Day 1, Month 3 and Month 7)
- Anti-HPV Neutralizing Titers in a Subset of Participants(At Month 2)
- Number of Participants With Seroconversion for Anti-HPV Neutralizing Antibodies(At Month 3 and Month 7)
- Correlation Between Anti-HPV IgG Antibody Concentration and Anti-HPV Neutralizing Antibody Titers(At Day 1, Month 2, Month 3 and Month 7)