A Phase 1b, Multicenter, Randomized, Placebo-controlled, Observer-blinded, Dose-escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity of the rSm-p80 + GLA-SE (SchistoShield®) Candidate Vaccine in Healthy Adults in Burkina Faso and Madagascar
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Proportion of participants with clinical safety laboratory adverse events measured at 7 days and 28 days after each study vaccination.
研究概览
简要总结
The goal of this phase 1b, multicenter, randomized, placebo-controlled, observer-blinded, dose-escalation study is to assess the safety, tolerability, and immunogenicity of a three-dose regimen, spaced four weeks apart, given intramuscularly in healthy adults (20-59 years old). Three different dose formulations of the study product with varying antigen contents will be investigated.
A total of 120 eligible participants will be recruited in 3 sequential cohorts (A, B, and C) in Burkina Faso (N=60) and in Madagascar (N=60). Cohort A will receive the low-dose antigen formulation (10 µg) or placebo, Cohort B will receive the medium-dose antigen formulation (30 µg) or placebo, and Cohort C will receive the high-dose antigen formulation (100 µg) or placebo; all antigens with 5 μg adjuvant (GLA-SE). In each cohort, volunteers will be randomized in a blinded manner into one of two arms, candidate vaccine or placebo, by a 3:1 ratio. A subset of five out of 20 subjects in each cohort will be sampled by convenience to enable us to further characterize the immune response using the peripheral blood mononuclear cells (PBMC). The Primary Objective of the study is to evaluate the safety and tolerability of 3 different dose formulations (low dose, medium dose, and high dose) of SchistoShield® vaccine given intramuscularly on D0, D28 and D56 to healthy participants 20 to 59 years of age in Burkina Faso and Madagascar.
详细描述
This is a phase 1b, multicenter, randomized, placebo-controlled, observer-blinded, dose-escalation study, assessing the safety, tolerability, and immunogenicity of a three-dose regimen, spaced four weeks apart, given intramuscularly in healthy adults (20-59 years old). Three different dose formulations of the study product with varying antigen contents will be investigated. A total of 120 eligible participants will be recruited in 3 sequential cohorts (A, B, and C) in Burkina Faso (N=60) and in Madagascar (N=60), as shown in the Table 1, below. Cohort A will receive the low-dose antigen formulation (10 µg) or placebo, Cohort B will receive the medium-dose antigen formulation (30 µg) or placebo, and Cohort C will receive the high-dose antigen formulation (100 µg) or placebo; all antigens with 5 μg adjuvant (GLA-SE). In each cohort, volunteers will be randomized in a blinded manner into one of two arms, candidate vaccine or placebo, by a 3:1 ratio. A subset of five out of 20 subjects in each cohort will be sampled by convenience to enable us to further characterize the immune response using the peripheral blood mononuclear cells (PBMC).
To ensure that the study participants at enrollment do not have any active schistosomiasis or helminth infection and are schistosomiasis egg-negative, pre-screening activities including schistosomiasis treatment will be carried out in potential study participants prior to enrollment. Potential study participants will be identified in the catchment population and will be offered anti-helminth treatment using praziquantel (PZQ) and Albendazole (ABZ) as per local guidelines at study site. The pre-screening visit will be conducted 6-8 weeks before the screening visit. The last dose of PZQ/ABZ will be administered at least 5 weeks prior to the first dose of study product.
The Primary objective is to evaluate the safety and tolerability of 3 different dose formulations (low dose, medium dose, and high dose) of SchistoShield® vaccine given intramuscularly on D0, D28 and D56 to healthy participants 20 to 59 years of age in Burkina Faso and Madagascar.
The Secondary objective is to evaluate the immunogenicity of 3 different dose formulations (low dose, medium dose, and high dose) of SchistoShield® vaccine 28 days post-vaccination on D28, D56, and D84 as compared with the baseline and with those who received placebo.
The Exploratory objective is to describe the antigen-specific B- and T-cell responses, memory responses, and innate and adaptive immune signatures from samples collected at specified timepoints.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The PI, study staff, and participants will be blinded as to receipt of study vaccine or placebo. The unblinded pharmacy staff preparing the study product syringes and the unblinded study nurse who is administering the product will not be involved in the safety assessment of participants and will be instructed not to comment on the experimental agent to study staff.
入排标准
- 年龄范围
- 20 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female participants aged 20 to 59 years at the time of consent.
- •Participant who has completed the deworming using praziquantel (PZQ) and albendazole (ABZ) according to local guidelines, with the last dose of PZQ/ABZ administered at least 5 weeks prior to first dose of study product.
- •Participant who, after the nature of the study has been explained, has voluntarily given informed consent, according to the local regulatory requirements, prior to study entry.
- •Participant who can comply with the study procedures and available for the entire duration of the study (32 weeks).
- •Individuals in good health as determined by the outcome of medical history, physical examination, hematology and biochemistry tests at the time of screening and the clinical judgment of the investigator.
- •Women of childbearing potential* with negative urinary test result on a human chorionic gonadotropin pregnancy test on the day of randomization, before receiving any study product.
- •Males or females of childbearing potential who are using an effective birth control method recommended by the national health system for at least four (4) weeks before the first vaccination (for female participants only) and up to four (4) weeks after the third vaccination (i.e., for at least 4 months).
排除标准
- •Participant with major congenital abnormalities which in the opinion of investigator may affect the subject's participation in the study.
- •Participant concomitantly enrolled or scheduled to be enrolled in another trial.
- •Positive rapid test for HIV 1-2 confirmed by a positive blood test for human immunodeficiency virus (positive antibodies to HIV 1/2).
- •Participant seropositive for hepatitis B virus surface antigen (HBsAg).
- •Participant seropositive for hepatitis C virus (Antibodies to HCV).
- •Participant with active or chronic Schistosomiasis infection defined by a positive result for microscopy (Urine filtration, Kato-Katz (KK)) and point-of-care - circulating cathodic antigen (POC -CCA) and/or real-time PCR.
- •Participant with soiled transmitted helminths infections (STH) as diagnosed by microscopy (KK) and/or real-time PCR.
- •Participant with malaria infection/malaria as diagnosed by the blood smear.
- •Any other confirmed or suspected immunosuppressive or immunodeficient state such as asplenia, recurrent severe infections.
- •Body mass index (BMI) ≥ 35 kg/m2
- •Chronic use of systemic steroids (>2 mg/kg/day or >20 mg/day prednisolone equivalent for periods exceeding 10 days), cytotoxic or other immunosuppressive drugs.
- •Receipt of blood or blood-derived products in the past 3 months.
- •Participant who has received other vaccines 4 weeks prior to test vaccination or plans to receive any vaccine within 4 weeks of last dose of study vaccine, exception made for COVID-19 vaccines.
- •Known history of allergy to study vaccine components and/or excipients or other medications, or any other allergies deemed by the investigator to increase the risk of an adverse event if they were to participate in the trial.
- •Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time resulting in contraindication for IM injections/blood extractions.
- •Any abnormality or chronic disease which in the opinion of the investigator might be detrimental for the safety of the participant and interfere with the assessment of the study objectives and compromise the health of the volunteers.
- •Any female participant who is lactating*, pregnant or planning for pregnancy** during the course of study period.
- •Individuals with behavioral or cognitive impairment or psychiatric disease or neural disorders that, in the opinion of the investigator, could interfere with the individual's ability to participate in the trial.
- •Any clinically significant abnormal finding on serum chemistry or hematology or urinalysis at the screening visit as per US FDA toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials (any biological finding grade 4 constitutes an exclusion criteria).
- •Individuals who were research staff involved with the clinical study or family/household members of research staff.
- •As per Investigator's medical judgement individual could be excluded from the study despite meeting all inclusion/exclusion criteria mentioned above.
研究组 & 干预措施
Cohort A
Cohort A will receive the low-dose antigen formulation(10 μg rSm-p80 + 5 μg GLA-SE) or placebo. Cohort will include 40 participants randomized to receive either Sm-p80 product or placebo in a 3:1 ratio. All participants will receive three intramuscular injections of 0.5 mL of the designated study product / placebo, on Days 0, 28, and 56 (28 days apart).
干预措施: rSm-p80 + GLA-SE (Biological)
Cohort B
Cohort B will receive the medium-dose antigen formulation(30 μg rSm-p80 + 5 μg GLA-SE) or placebo. Cohort will include 40 participants randomized to receive either Sm-p80 product or placebo in a 3:1 ratio. All participants will receive three intramuscular injections of 0.5 mL of the designated study product / placebo, on Days 0, 28, and 56 (28 days apart).
干预措施: rSm-p80 + GLA-SE (Biological)
Cohort C
Cohort C will receive the high-dose antigen formulation(100 μg rSm-p80 + 5 μg GLA-SE) or placebo. Cohort will include 40 participants randomized to receive either Sm-p80 product or placebo in a 3:1 ratio. All participants will receive three intramuscular injections of 0.5 mL of the designated study product / placebo, on Days 0, 28, and 56 (28 days apart).
干预措施: rSm-p80 + GLA-SE (Biological)
结局指标
主要结局
Proportion of participants with clinical safety laboratory adverse events measured at 7 days and 28 days after each study vaccination.
时间窗: Day 1 through Day 84
Proportion of participants with of any Serious Adverse Events (SAEs)/ adverse events of special interest (AESI) from the time of the first study vaccination through the final study visit.
时间窗: Day 1 through Day 224
Proportion of participants with immediate adverse events (reactogenicity events) within 60 min from the time of each study vaccination
时间窗: Day 1 through Day 56
Proportion of participants with unsolicited AEs from the time of vaccination until 28 days post immunization with the three different dose formulations.
时间窗: Day 1 through Day 84
Proportion of participants with solicited local and solicited systemic AEs as measured for 7 days (inclusive) following immunization with the three different dose formulations.
时间窗: Day 1 through Day 63
Proportion of Participants With of Any Serious Adverse Events (SAEs)/ Adverse Events of Special Interest (AESI) From the Time of the First Study Vaccination Through the Final Study Visit.
时间窗: Day 1 through Day 224
Serious Adverse Events (SAE) An AE or suspected adverse reaction is considered "serious" if at any dose (including overdose): Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent or significant disability/incapacity Is a congenital anomaly/birth defect ; or Is an important medical event that may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. Adverse Event of Special Interest (AESI) are AEs that are considered by the sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.
Proportion of Participants With Immediate Adverse Events (Reactogenicity Events) Within 60 Min From the Time of Each Study Vaccination
时间窗: Day 1 through Day 56
Immediate adverse events collected within 60 mins from the time of each study vaccination Local (Injection site) reactions collected include Pain, Tenderness, Pruritus (itching), Swelling, Erythema (Redness) and Induration (Hardness). Systemic symptoms collected include Chills, Myalgia (Body aches/Muscular pain), Arthralgia (Joint pain), Nausea, Vomiting, Headache, Dizziness, Malaise, Fatigue. Quantitative data regarding fever as a systemic reactogenicity parameter were collected.
Proportion of Participants With Solicited Local and Solicited Systemic AEs as Measured for 7 Days (Inclusive) Following Immunization With the Three Different Dose Formulations.
时间窗: Day 1 through Day 63
Local (Injection site) reactions collected include Pain, Tenderness, Pruritus (itching), Swelling, Erythema (Redness) and Induration (Hardness). Systemic symptoms collected include Chills, Myalgia (Body aches/Muscular pain), Arthralgia (Joint pain), Nausea, Vomiting, Headache, Dizziness, Malaise, Fatigue. Quantitative data regarding fever as a systemic reactogenicity parameter were collected.
Proportion of Participants With Unsolicited AEs From the Time of Vaccination Until 28 Days Post Immunization With the Three Different Dose Formulations.
时间窗: Day 1 through Day 84
Unsolicited adverse events (AEs) were defined as an untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Unsolicited AEs are all other adverse events (those that do not fall under the categories of solicited adverse reactions) that are identified by site staff, the PI and the Study Medical Monitor.
Proportion of Participants With Clinical Safety Laboratory Adverse Events Measured at 7 Days and 28 Days After Each Study Vaccination.
时间窗: Day 1 through Day 84
Clinical laboratory safety measurements collected include: Hematology \[Complete blood count (CBC) with automated differential\]: White blood cell (WBC) count, Red Blood Cell count (RBC), hemoglobin, and platelet count. Serum chemistry: alanine aminotransferase (ALT)/ aspartate aminotransferase (AST), Total Bilirubin (TB), Creatinine (CREAT), and C-reactive protein (CRP). Urine samples were be tested by dipstick for blood, glucose and protein. Labs samples were collected at screening and on vaccination days and 7 days and 28 days post each vaccination.
次要结局
- Geometric Mean Titers (GMTs) of serum Sm-p80 IgG antibodies at approximately 24 weeks after third dose of study vaccination.(Day 1 through Day 224)
- For Sm-p80 IgG antibodies, seroconversion rate at approximately 4 weeks (28 days) after each dose of study vaccination as compared to baseline(Day 1 through Day 84)
- Geometric Mean Titers (GMTs) of serum Sm-p80 IgG antibodies at approximately 4 weeks after each dose of study vaccination.(Day 1 through Day 84)
- For Sm-p80 IgG antibodies, seroconversion rate at approximately 24 weeks after third dose of study vaccination as compared to baseline(Day 1 through Day 224)
- For Sm-p80 IgG Antibodies, Seroconversion Rate at Approximately 4 Weeks (28 Days) After Each Dose of Study Vaccination as Compared to Baseline(Through 28 days after the first, second, and third study vaccinations)
- For Sm-p80 IgG Antibodies, Seroconversion Rate at Approximately 24 Weeks After Third Dose of Study Vaccination as Compared to Baseline(Through 24 weeks after third dose of study vaccination)
- Geometric Mean Titers (GMTs) of Serum Sm-p80 IgG Antibodies at Approximately 4 Weeks After Each Dose of Study Vaccination.(Through 28 days after the first, second, and third study vaccinations)
- Geometric Mean Titers (GMTs) of Serum Sm-p80 IgG Antibodies at Approximately 24 Weeks After Third Dose of Study Vaccination.(Through 24 weeks after third dose of study vaccination.)