A Phase I/II, Observer-Blind, Randomized, Placebo-Controlled, Dose-Selection Study to Assess the Safety, Tolerability, and Immunogenicity of Hexavalent Group B Streptococcus Conjugate Vaccine Manufactured by Inventprise, Inc., in Healthy, Non-Pregnant, Adult Women of Childbearing Age (WOCBA) in the US and South Africa.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 600
- 试验地点
- 2
- 主要终点
- Safety -percentage of participants reporting immediate AE within 30 minutes of vaccination
研究概览
简要总结
To assess the safety and tolerability of IVT GBS-06 vaccine administered as a single-dose regimen, at three dosage levels in healthy, non-pregnant, adult women of childbearing age (WOCBA).
详细描述
This is a phase I/II, randomized, placebo-controlled, observer-blinded trial to evaluate the safety, tolerability, and immunogenicity of a multivalent GBS vaccine candidate in healthy, non-pregnant, adult WOCBA, 18-49 years of age, at two sites, one each in the US and South Africa. Approximately 600 participants will be randomized to receive a single dose of low, mid, or high concentration of IVT GBS-06, or a placebo (saline control) at Day (D)1, administered IM by injecting 0.5 mL into the deltoid muscle. The three dose levels denote the amount of capsular polysaccharide (CPS) for each of the six serotypes per 0.5 mL. These four study groups will be enrolled simultaneously to allow for parallel assessments of overall IVT GBS-06 safety and tolerability. Participants will be randomized in a 1:1:1:1 ratio to one of the dose levels or placebo. This study will utilize a sentinel-cohort design in which 20 participants overall (i.e., N=5 per treatment arm) at the US site will be randomized, vaccinated, and evaluated for safety prior to opening enrolment of additional participants in USA and in South Africa. This study targets representation from both study populations and therefore at least 220 participants will be recruited from each of the two sites and will allow competitive enrollment across the two study sites for the remaining 160 participants to reach 600 within target enrollment period.
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
Subjects randomized 1:1:1:1, placebo-controlled, observer blinded
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy women aged 18-49 years (inclusive) at enrollment.
- •Healthy, as defined by the absence of any clinically significant medical conditions, either acute or chronic, as determined by medical history, physical examination, screening laboratory test results, and clinical assessment of the investigator. Participants with stable chronic conditions may be enrolled in the study at the discretion of the investigator. Stable conditions are conditions that do not require changes to medication or other interventions in the past 6 weeks.
- •Willing and able to provide written informed consent prior to performance of any study specific procedure.
- •If of childbearing potential*, not be breastfeeding and not be pregnant (based on a negative serum pregnancy test at screening and a negative urine pregnancy test during the 24 hours prior to study vaccination) and having practiced adequate contraception** for at least 30 days prior to study vaccination and willing to continue using adequate contraception consistently throughout the study.
- •Participants can be considered not of childbearing potential if they meet at least 1 of the following criteria:
- •Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state.
- •Have undergone a documented hysterectomy and/or bilateral oophorectomy.
- •Have medically confirmed ovarian failure.
- •They identify as transgender women and do not have ovaries or a uterus. All other participants (including participants with tubal ligations) are considered to be of childbearing potential.
- •** Adequate contraception is defined as a contraceptive method with a failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label, for example:
- •Abstinence from penile-vaginal intercourse
- •Combined estrogen and progesterone oral contraceptives
- •Hormonal (e.g., progestogen) injections
- •Hormonal (e.g., etonogestrel or levonorgestrel) implants
- •Contraceptive vaginal ring
- •Percutaneous contraceptive patches
- •Intrauterine device
- •Intrauterine hormonal system
- •Resides in the study area and is able and willing to adhere to all study restrictions and to all study visits and procedures including completion of seven day post-injection memory aid (as evidenced by a signed informed consent form and assessment by the investigator).
排除标准
- •Participants meeting any of the following criteria will be excluded from participation:
- •Presence of an acute disease within 72 hours prior to enrollment - temporary exclusion*.
- •Presence of recorded fever (axillary temperature ≥ 37.5°C or oral temperature of ≥ 37.5°C) or use of an antipyretic medication within 72 hours prior to enrollment- temporary exclusion *.
- •Presence of an abnormal (> Grade 2) vital sign measurement (heart rate, blood pressure[systolic or diastolic], respiratory rate) - temporary exclusion*
- •Laboratory confirmed active infection with human immunodeficiency virus, chronic hepatitis B virus infection (hepatitis B virus surface antigen positive), or hepatitis C virus infection. HCV RNA negative (if tested) may be allowed.
- •BMI <17 or ≥ 40 kg/m2
- •Presence of any chronic or degenerative neurological disease or history of significant neurological disorder (e.g., dementia, meningitis, seizures, multiple sclerosis, vasculitis, or Guillain-Barré syndrome), genetic/congenital or acquired.
- •Evidence of a major depression disorder not well controlled in the past 2 years prior to screening (by history and medication review, at discretion of the investigator) or history of suicidal ideation or attempt in the past 2 years prior to screening.
- •History of severe adverse reaction and/or severe allergic reaction (e.g., anaphylaxis) to polyethylene glycol (PEG) or any vaccine.
- •History of microbiologically proven invasive disease caused by GBS (S. agalactiae) or receipt of any investigational GBS vaccine.
- •Participation in another investigational product (drug or vaccine) clinical trial within 30 days prior to enrollment in this study or receipt of any such investigational product other than the study vaccine within 30 days prior to administration of study vaccine or planned use during the study period.
- •Immunocompromising condition with known or suspected immunodeficiency.
- •Prior use of or anticipated need of any long-acting immunomodulating drug (e.g., infliximab or rituximab cytotoxic agents), or chronic administration (defined as more than 14 days) of high dose (≥ 20 mg of prednisolone or equivalent/day) systemic corticosteroids during the study period. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 30 days before investigational product administration. Inhaled/nebulized, intra-articular, intra-bursal, or topical (skin or eyes) corticosteroids are permitted.
- •Indications of drug abuse or excessive use of alcohol as deemed by the investigator to confound safety assessments or render the participant unable or unlikely to adhere to protocol requirements or provide accurate safety reports.
- •Administration of any vaccine other than the study vaccine within 28 days prior to or after study vaccination. Exceptions of seasonal inactivated influenza and COVID-19 vaccines which are prohibited for only 14 days prior to or following study vaccination is applicable.
- •Receipt of transfusion of any blood product or application of immunoglobulins within the 12 weeks prior to the administration of study vaccine or planned use during the study period.
- •Any planned surgery during the study period that would require hospitalization, use of prohibited medication, or will interfere with follow-up visits.
- •History of known disturbance of coagulation or blood disorder that could cause anemia or excess bleeding.
- •Participant is an employee of, or close personal relation of any person employed by the Sponsor, PATH, the CRO, the PI, or key study site personnel.
- •History of malignancy, excluding non-melanoma skin and cervical carcinoma in situ.
- •Any other acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for enrollment into this study.
- •Any screening laboratory value that meets the criteria specified below will be excluded from study participation:
- •Hemoglobin < 10.0 g/dL.
- •White blood cells (WBC) increased > 15,000 cells/mm3
- •WBC decreased < 2,600 cells/L
- •Platelet count < 125,000 cells/mm3
- •Creatinine >1.8 mg/dL or 159.1 µmol/L
- •Alanine aminotransaminase (ALT) > 2.5 × the upper limit of normal (ULN)
- •Total bilirubin > 1.5 × ULN
研究组 & 干预措施
Group 1; GBS-06 (Low)
Participants will receive a single 0.5mL dose of IVT GBS-06 Formulation 1 (low dose polysaccharide concentration) administered by intramuscular injection to the non-dominant deltoid muscle on Day 1.
干预措施: IVT GBS-06 (Biological)
Group 2; GBS-06 (Mid)
Participants will receive a single 0.5mL dose of IVT GBS-06 Formulation 2 (mid-dose polysaccharide concentration) administered by intramuscular injection to the non-dominant deltoid muscle on Day 1.
干预措施: IVT GBS-06 (Biological)
Group 3; GBS-06 (High)
Participants will receive a single 0.5mL dose of IVT GBS-06 Formulation 3 (high dose polysaccharide concentration) administered by intramuscular injection to the non-dominant deltoid muscle on Day 1.
干预措施: IVT GBS-06 (Biological)
Group 4; Placebo
Participants will receive a single 0.5mL dose of 0.9% sodium chloride placebo administered by intramuscular injection to the non-dominant deltoid muscle on Day 1.
干预措施: Placebo (Biological)
结局指标
主要结局
Safety -percentage of participants reporting immediate AE within 30 minutes of vaccination
时间窗: 30 minutes after vaccination
The percentage of participants reporting immediate AE within 30 minutes of vaccination.
Safety - percentage of participants reporting solicited local adverse events (AEs) within 7 days of vaccination
时间窗: Day 1 - Day 7 after vaccination
The percentage of participants reporting solicited local adverse events (AEs) within 7 days following study vaccination (pain, redness and swelling/induration at the injection site).
Safety- percentage of participants reporting solicited systemic AEs within 7 days following study vaccination (fever, fatigue, headache, chills, myalgia, arthralgia, and nausea/vomiting)
时间窗: Day 1 - Day 7 after vaccination
The percentage of participants reporting solicited systemic AEs within 7 days following study vaccination (fever, fatigue, headache, chills, myalgia, arthralgia, and nausea/vomiting)
Safety - percentage of participants reporting unsolicited AEs within 28 days following study vaccination
时间窗: Day 1 - Day 28 after vaccination
The percentage of participants reporting unsolicited AEs within 28 days following study vaccination
Safety - percentage of participants with clinically significant laboratory abnormalities within 7 days following study vaccination
时间窗: Day 1 - Day 7 after vaccination
The percentage of participants with clinically significant laboratory abnormalities within 7 days following study vaccination
Safety - percentage of participants reporting medically attended adverse events (MAAEs)
时间窗: From Day 1 vaccination through the end of study
The percentage of participants reporting medically attended adverse events (MAAEs)
Safety - percentage of participants reporting serious adverse events (SAEs)
时间窗: From Day 1 vaccination through the end of study
The percentage of participants reporting serious adverse events (SAEs)
次要结局
- Immunogenicity - IgG(Day 1 baseline collection and 4-weeks post dose collection)
- Immunogenicity(Day 1 baseline collection and 4-weeks post dose collection)
- Immunogenicity - OPA(Day 1 baseline collection and 4-weeks post dose collection)