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Study of Safety and Effectiveness of Intravenous Immunization With PfSPZ Vaccine in Healthy African Adults

Phase 1
Completed
Conditions
Malaria
Interventions
Biological: PfSPZ Vaccine
Drug: Placebo
Registration Number
NCT01988636
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

Background:

- Malaria is caused by small germs carried by mosquitoes. People can get malaria if an infected mosquito bites them. Malaria destroys red blood cells and reduces oxygen in the blood. Most malaria is mild, but severe malaria kills at least 660,000 people each year. About 75% of these are children in Sub-Saharan Africa, most under age 5. Researchers want to find a safe vaccine that helps prevent malaria.

Objectives:

- To see if a new malaria vaccine is well tolerated and effective.

Eligibility:

- Healthy adults 18 35 years old who are not pregnant and live in Mali.

Design:

* Participants will be screened with medical history, physical exam, and blood test. They will also have an ECG. Soft electrodes will be stuck to the skin. A machine will record the heart s electrical signals.

* Study participation will last about 1 year.

* Participants will be randomly placed in 5 groups. Some will get 2 doses of the PfSPZ vaccine weeks apart; some will get 3 or 5 doses of vaccine; some will get 3 or 5 doses of placebo.

* Doses will be given through a needle in the arm directly into the bloodstream. Then participants must stay at the clinic for 2 hours.

* After each dose, participants will return to the clinic several times for blood tests and physical exam.

* A week before the first dose and 2 weeks after the last, participants will take a full course of anti-malaria drugs.

* If a participant gets malaria during the study, they will take another course of anti-malaria drugs.

Detailed Description

For decades 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. 1 has developed a process for manufacturing, in compliance with current Good Manufacturing Practices (cGMPs) aseptic, purified, radiation attenuated cryopreserved sporozoites from a wellcharacterized isolate of P. falciparum. This product, which is called PfSPZ Vaccine, can be administered by needle and syringe. Previous studies conducted by the Vaccine Research Center, National Institutes of Health (NIH) 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.

The next logical step is to test the safety and immunogenicity of PfSPZ Vaccine in malaria experienced individuals. As an exploratory objective, this study will collect initial data to find out if the vaccine can protect against naturally occurring infection. Here, we propose a randomized double blind controlled trial to assess the safety and immunogenicity of IV administration of PfSPZ Vaccine in African adults.

Subjects will be recruited from a rural village in Mali. The study will be 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. Group 1 (n=12), will receive 135,000 PfSPZ Vaccine, followed by 270,000 PfSPZ Vaccine 2 weeks later for safety purposes. An independent Data Safety Monitoring Board (DSMB) will determine whether it is safe to proceed with 270,000 PfSPZ Vaccine.

At Study Week 4, Group 4 (n=50) will receive their first of 5 doses of 270,000 PfSPZ Vaccine given at 4, 8, 12, 16, and 24 weeks, alongside Group 5 (n=50) receiving a similar volume placebo. Safety data will be collected at defined time points after each immunization. From Week 28 until Week 48 all subjects will be monitored for parasitemia detected by slide microscopy every 14 days and by passive case detection.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
296
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Group 1PfSPZ VaccinePilot Safety Group- 135000 PfSPZ + 270000 PfSPZ; staggered at Day 0 and 2 weeks
Group 4PfSPZ VaccineGroup to start at week 4 after Group 1 is deemed safe - 5 immunizations of 270000 PfSPZ at weeks 4, 8, 12, 16 and 24
Group 5PlaceboGroup to receive placebo at same points as Group 4 - 5 immunizations of normal saline at weeks 4, 8, 12, 16 and 24
Primary Outcome Measures
NameTimeMethod
Assess the safety of repeated IV immunizations with PfSPZ Vaccine28 days
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

University of Bamako

🇲🇱

Bamako, Mali

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