Dose Escalating and Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) in Healthy African Adults in Mali
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 409
- 试验地点
- 1
- 主要终点
- Duration
研究概览
简要总结
Background:
Malaria is still a health problem in Sub-Saharan Africa. Death rates are stable and have even increased in some areas. There are malaria vaccines. However, researchers think repeated immunizations with a vaccine called PfSPZ may work better.
Objective:
To see if PfSPZ is safe, tolerable, and effective against malaria.
Eligibility:
Healthy adults ages 18 to 50 years who live in the Doneguebougou area in Mali
Design:
Participants will be screened with medical history and physical exam.
Participants will sign or fingerprint the consent form. They will take a survey to see how well they understand the study.
Participants will give blood and urine samples.
Participants will have at least one ECG: Soft electrodes will be stuck to the skin. A machine will record heart signals.
Participants will have HIV counseling.
Participants will be assigned to a group. Groups will get a different strength doses. Groups will get a different number of vaccines over different periods of time.
If a participant develops a rash or injection site reaction, photographs may be taken.
Participants will receive an oral anti-malaria drug during the study.
Participants will be monitored for 3 to 6 months after the last vaccine.
详细描述
It is known that humans can be protected against malaria by repeated immunization with radiation attenuated sporozoites. Traditionally, those sporozoites are administered by exposing the vaccinee to at least 1000 bites of sporozoite infected irradiated mosquitoes, an approach that is unsuitable for mass vaccination campaigns. Recently, Sanaria, Inc. developed a process for manufacturing, in compliance with current Good Manufacturing Practices (cGMPs) aseptic, purified, radiation attenuated cryopreserved sporozoites from a well characterized isolate of P. falciparum (Hoffman et al., 2010). This product, which is called PfSPZ Vaccine, can be administered by needle and syringe. Previous studies conducted by the Vaccine Research Center and the Navy have established that IV administration of PfSPZ Vaccine can induce sterile protection against controlled human malaria infection (CHMI) with a homologous strain of P. falciparum in up to 100% of malaria na(SqrRoot) ve individuals (Seder et al., 2013). A recent study conducted as collaboration among the Malaria Research and Training Center (MRTC, Mali), the Laboratory of Malaria Immunology and Vaccinology (LMIV) National Institute of Allergy and Infectious Diseases (NIAID), and Sanaria, Inc. (Sissoko et al., unpublished) has shown that sterile protection against naturally occurring malaria infection can be achieved, but not at the level seen in the US nor at the level desired.
The next logical step in an attempt to improve protective efficacy in the targeted endemic population is to increase the PfSPZ Vaccine dose, increasing the interval between the first and second doses to 8 weeks (as was done in WRAIR 2080 in the group receiving 3 doses of 4.5x105 PfSPZ), and reducing the numbers of doses to three. Additionally, in this study design, we also can begin to understand how the standard controlled human malaria infection (CHMI) model may be used in the field and start to explore the impact of such factors as malaria co infection and drug treatment have on vaccine responses.
The initial dose escalation pilot study will focus on safety and tolerability of the PfSPZ Vaccine. A defined number of subjects enrolled during the pilot study will also undergo further evaluation, including randomization to receive or not receive drug treatment immediately prior to each vaccination and examination of protective efficacy against homologous CHMI via PfSPZ Challenge. The targeted dose (18x105 PfSPZ Vaccine), if safe and tolerable, will be administered to a larger cohort in a double blind, randomized, placebo controlled trial to examine the protective efficacy of the vaccine against naturally occurring infection. PfSPZ Vaccinees (Arm 2) from the main study will be re enrolled the following malaria transmission along with age, sex, and village matched controls (re enrolled Arm 3, additional controls) to explore the duration of protection through another malaria transmission season.
Subjects will be recruited from rural villages in Mali. The study will be conducted as collaboration among MRTC, LMIV/NIAID, and Sanaria, Inc.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1A
(n=5), will be a safety group. Subjects will receive 1 dose of PfSPZ Vaccine (4.5x105) via DVI. All 5 subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to PfSPZ Vaccine. Subjects will be followed for approximately 3 months post vaccination.
干预措施: PfSPZ Vaccine (Biological)
1A
(n=5), will be a safety group. Subjects will receive 1 dose of PfSPZ Vaccine (4.5x105) via DVI. All 5 subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to PfSPZ Vaccine. Subjects will be followed for approximately 3 months post vaccination.
干预措施: PBS and HSA Diluent (Drug)
1A
(n=5), will be a safety group. Subjects will receive 1 dose of PfSPZ Vaccine (4.5x105) via DVI. All 5 subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to PfSPZ Vaccine. Subjects will be followed for approximately 3 months post vaccination.
干预措施: ASAQ (Drug)
1B
(n=S), will be a safety group. Subjects will receive 1 dose of PfSPZ Vaccine (9.0x10S) via DVI. All S subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to PfSPZ Vaccine. Subjects will be followed for approximately 3 months post vaccination
干预措施: PfSPZ Vaccine (Biological)
1B
(n=S), will be a safety group. Subjects will receive 1 dose of PfSPZ Vaccine (9.0x10S) via DVI. All S subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to PfSPZ Vaccine. Subjects will be followed for approximately 3 months post vaccination
干预措施: PBS and HSA Diluent (Drug)
1B
(n=S), will be a safety group. Subjects will receive 1 dose of PfSPZ Vaccine (9.0x10S) via DVI. All S subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to PfSPZ Vaccine. Subjects will be followed for approximately 3 months post vaccination
干预措施: ASAQ (Drug)
1D
(n=15), will be the CHMI control group. Subjects will not receive any PfSPZ vaccinations but will serve as infectivity controls for CHMI. All 15 subjects will receive antimalarial treatment with ASAQ prior to PfSPZ Challenge.
干预措施: PBS and HSA Diluent (Drug)
1C
(n=30), will be the targeted dose for the Pilot Safety Group. Subjects will receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. 15 subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to each administration of PfSPZ Vaccine, while 15 will not, except prior to PfSPZ Vaccine #3 when all 30 subjects will receive antimalarial treatment with ASAQ.
干预措施: PfSPZ Vaccine (Biological)
1C
(n=30), will be the targeted dose for the Pilot Safety Group. Subjects will receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. 15 subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to each administration of PfSPZ Vaccine, while 15 will not, except prior to PfSPZ Vaccine #3 when all 30 subjects will receive antimalarial treatment with ASAQ.
干预措施: PfSPZ Challenge Material (Biological)
1C
(n=30), will be the targeted dose for the Pilot Safety Group. Subjects will receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. 15 subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to each administration of PfSPZ Vaccine, while 15 will not, except prior to PfSPZ Vaccine #3 when all 30 subjects will receive antimalarial treatment with ASAQ.
干预措施: PBS and HSA Diluent (Drug)
1C
(n=30), will be the targeted dose for the Pilot Safety Group. Subjects will receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. 15 subjects will receive antimalarial treatment with artesunate /amodiaquine (ASAQ) prior to each administration of PfSPZ Vaccine, while 15 will not, except prior to PfSPZ Vaccine #3 when all 30 subjects will receive antimalarial treatment with ASAQ.
干预措施: ASAQ (Drug)
1D
(n=15), will be the CHMI control group. Subjects will not receive any PfSPZ vaccinations but will serve as infectivity controls for CHMI. All 15 subjects will receive antimalarial treatment with ASAQ prior to PfSPZ Challenge.
干预措施: PfSPZ Challenge Material (Biological)
1D
(n=15), will be the CHMI control group. Subjects will not receive any PfSPZ vaccinations but will serve as infectivity controls for CHMI. All 15 subjects will receive antimalarial treatment with ASAQ prior to PfSPZ Challenge.
干预措施: ASAQ (Drug)
2
(n=60), will be the targeted vaccine dose arm and receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. All subjects will receive antimalarial treatment prior to Vaccination #1 and #3 unless results obtained and analyzed from the pilot study indicate otherwise.
干预措施: PfSPZ Vaccine (Biological)
2
(n=60), will be the targeted vaccine dose arm and receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. All subjects will receive antimalarial treatment prior to Vaccination #1 and #3 unless results obtained and analyzed from the pilot study indicate otherwise.
干预措施: PBS and HSA Diluent (Drug)
2
(n=60), will be the targeted vaccine dose arm and receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. All subjects will receive antimalarial treatment prior to Vaccination #1 and #3 unless results obtained and analyzed from the pilot study indicate otherwise.
干预措施: Coartem (Drug)
2
(n=60), will be the targeted vaccine dose arm and receive 3 doses of PfSPZ Vaccine (18x105) via DVI on Day 1, 57, 113. All subjects will receive antimalarial treatment prior to Vaccination #1 and #3 unless results obtained and analyzed from the pilot study indicate otherwise.
干预措施: ASAQ (Drug)
3
(n=60), will be the placebo arm and receive vaccinations with normal saline via DVI on Day 1, 57, 113. All subjects will receive antimalarial treatment prior to Vaccination #1 and #3 unless results obtained and analyzed from the Pilot Study indicate otherwise.
干预措施: Normal Saline (Other)
3
(n=60), will be the placebo arm and receive vaccinations with normal saline via DVI on Day 1, 57, 113. All subjects will receive antimalarial treatment prior to Vaccination #1 and #3 unless results obtained and analyzed from the Pilot Study indicate otherwise.
干预措施: ASAQ (Drug)
4
(n=SS), will be group- matched (age, sex, village) controls for Arm 2 for the duration study. Subjects previously enrolled in Arm 3 may re-enroll in Arm 4. All subjects will receive antimalaria treatment at enrollment
干预措施: Coartem (Drug)
结局指标
主要结局
Duration
时间窗: For 24 weeks starting approximately 1 year post vaccination #3
P. falciparum blood stage infection defined as time to first positive blood smear (detection of at least 2 P. falciparum parasites by microscopic examination of 0.5 muL)
Safety
时间窗: Approximately within 7 days after each vaccination and SAEs related to vaccination
Measure the incidence and severity of local and systemic adverse events occurring within 7 days after each vaccine administration and SAE related to vaccination.
次要结局
- Protective Efficacy (pilot phase)(Immediately following PfSPZ CHMI)
- Protective Efficacy (main phase)(Immediately following 3rd vaccination)