A Phase 1b/2b Double Blind, Randomized, Controlled Study of the Safety, Immunogenicity, and Efficacy of Malaria Vaccine Candidate MSP3-CRM-Vac4All/ Alhydrogel® in Young Children in Mali
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 465
- 试验地点
- 2
- 主要终点
- Protective Efficacy against Clinical Malaria
研究概览
简要总结
Two-arm, randomized, double-blinded and controlled clinical trial to first assess the safety and tolerability of the vaccine in a Phase 1b trial and proceed to assess its efficacy against clinical malaria in young children living in highly seasonal malaria areas of Mali
详细描述
This study is designed to be executed in two steps to achieve the primary efficacy objective:
The first step is a Phase 1b safety study, involving injections in a small safety subgroup for each dose before age-de-escalation into the younger age group and then proceeding to the second step of dosing the corresponding injection in the larger Phase 2b efficacy cohort.
Vaccination of the Phase 2b cohort will require an acceptable reactogenicity data over the first week following the corresponding vaccination of the older and younger age groups in the Phase 1 subgroup. The study DSMB will be charged with this review and ensuring that vaccination proceeds only if the reactogenicity profile meet study "go" criteria (Table 1).
The objectives of each phase are:
Phase 1b: The primary objective is to assess the safety and tolerability of the vaccine for each injection. The secondary objective is to evaluate the immune response to the vaccine and safety for up to 12 months after the first dose.
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
Vaccine recipients and their parent(s)/guardian(s) as well as all investigators and study personnel responsible for the vaccination, evaluation of safety and immunogenicity endpoints will all be unaware to the exact treatment given to the participant. Randomization will be programmed into the eCRF, as subjects are confirmed to be eligible for enrollment and to be vaccinated. A password protected electronic randomized vaccination allocation list will be sent to the designated vaccine pharmacist. The investigator will send a request for vaccination to the pharmacy using the subject randomization number (which will be the subject unique ID number) assigned by the eCRF. For each child, eligibility will have to be counter checked and signed by a second person before allocation of study ID number.
入排标准
- 年龄范围
- 12 Months 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Children aged 12-59 months years 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 participants
- •Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior recruitment. (For corticosteroids, this will mean prednisone, or equivalent, more or equal to 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.
- •Clinically significant 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 childhood immunization program or licensed vaccine (measles, oral polio, Hib, meningococcal and combined diphtheria/pertussis/tetanus vaccines) which may be given 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 based on clinical judgement.
- •o (Weight-for-age Z score of less than -3 or other clinical signs of malnutrition).
- •Previous participation to a malaria vaccine trial
- •Known history of HIV infection
结局指标
主要结局
Protective Efficacy against Clinical Malaria
时间窗: The timeline for assessment will be from 14 days to 6 months after Dose 3.
To assess the efficacy of 30 µg MSP3-CRM-Vac4All/Alhydrogel® vaccine in children ages 12-60 months old, against clinical malaria occurring over one transmission season. The primary efficacy outcome is clinical malaria, with the primary case definition of clinical malaria episodes defined as a febrile episode with an axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥5000/µL
次要结局
- Efficacy duration(For 12 months following the first vaccination)
- Efficacy (conditional boost)(For the 12 months following boost vaccination)
- Number of adverse events(During the month following each vaccination, and 6 months and 12 months after first vaccination.)
- Parasite densities(From vaccination to up to 6 months after last dose and 12 months after first dose.)
- Efficacy- different definitions of malaria fever and parasite thresholds on microscopy(For 12 months after first vaccination)
- Efficacy against first malaria episodes(From 14 days post 2nd or 3rd vaccination to 6 months following and up to the end of study follow-up (12 months after first vaccination)
- Immune response(A month after dose 3)
- Number of adverse events for conditional boost vaccination(At one month, 6 month and 12 months following boost vaccination)