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)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 1,080
- 试验地点
- 1
- 主要终点
- Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 1
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Observer-blinded for study vs comparator vaccine; double-blinded for 3 formulations of study vaccine
入排标准
- 年龄范围
- 16 Years 至 26 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: HPV9 High formulation (Biological)
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.
干预措施: HPV9 Medium formulation (Biological)
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.
干预措施: HPV9 Low formulation (Biological)
Gar9 Group
Participants received 3 doses of the marketed Human Papilloma Virus (HPV) vaccine (Gardasil 9) at Day 1, Month 2, and Month 6.
干预措施: Gardasil 9 (Biological)
结局指标
主要结局
Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 1
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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)