Phase 2B Double Blind, Randomized, Controlled Trial to Evaluate the Safety, Immunogenicity and Protective Efficacy of MSP3-LSP Vaccine Candidate Adjuvanted in Aluminium Hydroxide (AIOH) Against Plasmodium Falciparum Clinical Malaria in Healthy Children Aged 12-48 Months in Mali
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 800
- 试验地点
- 2
- 主要终点
- Number of episodes of clinical malaria occurring during a period beginning from 14 days after the 3rd immunization until 3 months after 3rd immunization in all subjects.
研究概览
简要总结
Hypothesis: The MSP3-LSP/Alum vaccine, administered to children will have a protective efficacy of at least 30% (lower bound of confidence interval of 0) against malaria disease occurring during a period beginning from 14 days after the 3rd immunization until 1 year after.
The primary objective of this double-blind, randomized, controlled trial will be to assess the clinical efficacy of MSP3-LSP/AlOH vaccine when administered by subcutaneous route in children aged 12-48 months against all clinical malaria episodes occurring during a period beginning from 14 days after the 3rd immunization until 3 months after 3rd immunization, when administered according to the following schedule:- Primary administration: Three doses of administered 4 weeks apart
Secondary administration (Boost): One dose 3 months after the third dose in year 1 of the trial; and two doses, given exactly one year after the date corresponding to the third dose and the first boost given during Year 1
Case definition for an episode of malaria is a febrile illness with axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥ 5000 per μL
详细描述
This is a Phase 2 b, randomized, controlled trial, comparing MSP3-LSP experimental malaria vaccine with the comparator Verorab rabies vaccine (primary series) and normal saline (secondary/booster series). The trial is being conducted in two sites, Doneguebougou and surroundings (Koulikoro) and Bougoula Hameau and surroundings (Sikasso).
Each site will enroll 400 subjects. Subjects aged 12-48 months will be enrolled and randomized in a 1:1 ratio to receive either 30 µg of MSP3-LSP/AlOH in 0.5 mL or the control vaccine, Verorab Rabies subcutaneously.
The primary series of vaccinations will be given on days 0, 28 and 56. The first of the secondary/booster series will be administered 3 months after completing the primary series (D146) in Year 1, and the subsequent booster doses will be administered one year after the 3rd dose (D416) and one year after the first booster dose (D506) in Year 2.
For safety, occurrence of adverse events will be solicited during daily home visit by field workers for 6 days after each vaccination. Unsolicited adverse events will be documented for the following 28 days after each dose.
For efficacy, suspect cases will be detected through weekly home visits following the 1st vaccination and continuing throughout the duration of the trial.
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)
入排标准
- 年龄范围
- 12 Months 至 48 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Children aged 12-48 months old
- •Healthy by medical history, physical examination and laboratory investigation
- •Signed/thumb printed informed Consent by guardian/parent
- •Resident in the study area villages during the whole trial period
排除标准
- •Symptoms, physical signs of disease that could interfere with the interpretation of the trial results or compromising the health of the subjects
- •Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior recruitment. (for corticosteroids, this will mean prednisone, or equivalent, ≥ 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
- •Cannot be followed for any social, psychological or geographical reasons.
- •Use of any investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use up to 30 days after the third dose.
- •Suspected or known hypersensitivity to any of the vaccine components or to previous vaccine.
- •Laboratory abnormalities on screened blood samples.
- •Planned administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine. An exception, is the receipt of an EPI or licensed vaccine (measles, oral polio, Hib, meningococcal and combined diphtheria/pertussis/tetanus vaccines) which may be given 14 days or more before or after vaccination
- •Evidence of chronic or active hepatitis B or C infection
- •Presence of chronic illness that, in the judgment of the investigator, would interfere with the study outcomes or pose a threat to the participant's health.
- •Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period
- •History of surgical splenectomy.
- •Moderate or severe malnutrition at screening defined as weight for age Z-score less than 2
结局指标
主要结局
Number of episodes of clinical malaria occurring during a period beginning from 14 days after the 3rd immunization until 3 months after 3rd immunization in all subjects.
时间窗: 3 months
A clinical malaria episode is defined as a febrile illness with a documented axillary temperature of
次要结局
- Number of subjects with solicited adverse events(7 days following each vaccination)
- Number of subjects with unsolicited adverse events(30 days following each vaccination)
- Number of subjects with serious adverse events(2 years)