Pfs230D1M-EPA/AS01 Vaccine, a Transmission Blocking Vaccine Against Plasmodium Falciparum, in an Age De-Escalation Trial of Children and a Family Compound Trial in Mali
- Conditions
- Malaria
- Interventions
- Biological: TYPHIM Vi (Salmonella typhi vaccine)
- Registration Number
- NCT03917654
- Brief Summary
Background:
Malaria affects many people in Mali and other parts of Africa. It is spread by mosquito bites. Malaria can make people sick or can lead to death. Scientists want to learn if a vaccine can stop it from spreading to other people.
Objective:
To test how well an experimental malaria vaccine works to decrease malaria infections.
Eligibility:
Healthy people ages 5 and older who live in Doneguebougou, Mali, and surrounding areas
Design:
Participants will be screened with:
Medical history
Physical exam
Blood, urine, and heart tests
EKG
Participants will be randomly assigned to get either the experimental vaccine or an approved vaccine. They will not know which they are getting.
Participants will have a visit about a week before their first vaccine. They will take a medicine that kills malaria. They will take it at the clinic the next 2 days. Participants ages 5-8 will take the drug again 2 weeks before their third vaccine.
Participants get the vaccine through a needle in the arm. They will have visits 1, 3, 7, and 14 days after. They will have blood tests or finger pricks.
Participants will get another vaccine 1 and 6 months later.
Participants will have blood tests once a month. At these visits they may also have urines tests or mosquito feeds. For the feeds a cup full of mosquitoes will be placed on arms or legs for 15-20 minutes.
Participants will have visits twice a month for 4 months after their last vaccine.
- Detailed Description
A vaccine to interrupt malaria transmission (VIMT), targeting disruption of both human and mosquito transmission, would be a valuable tool for local elimination or eradication of this disease. One strategy to design a VIMT is using components that block transmission of malaria to mosquitoes, such as Pfs230. Pfs230, a surface antigen of intracellular gametocytes, as well as extracellular gametes and zygotes in the mosquito stage of Plasmodium falciparum, is currently the leading candidate in clinical trials for a malaria transmission-blocking vaccine (TBV). Recombinant Pfs230D1M has been conjugated to a recombinant Pseudomonas aeruginosa ExoProtein A (EPA) and adjuvanted with AS01. When formulated in AS01, results from a recent first-in-human trial demonstrated that Pfs230-EPA induces functional transmission-reducing, and in a significant proportion of vaccinees, transmission-blocking serum activity that can be measured for months, the vaccine is well-tolerated and safe in adults, and our recent natural history data clearly indicate that children play a disproportionate role in malaria transmission. The next step in the development of Pfs230D1M-EPA as a TBV is therefore to conduct an age de-escalation trial to ensure that the vaccine is safe to administer to children and then to conduct a community clinical trial to assess efficacy in family groups.
This Phase 2 study will first determine safety and tolerability of Pfs230D1M-EPA/AS01 in healthy Malian children of decreasing ages: 9-18 years old, followed by 5-8 years old. A total of 60 subjects will be enrolled in Doneguebougou, Mali, West Africa. Children will be recruited from compounds/family that have agreed to participate in the main phase of the study and will enroll in a staggered manner to receive either Pfs230D1M-EPA/AS01 vaccine or comparator as assigned by their compound block randomization. Prior to receipt of vaccination #1, all subjects will receive a full treatment course of artemether/lumefantrine (AL). Safety and tolerability will be monitored and reported as local and systemic adverse events (AEs) and serious adverse events (SAEs) and reviewed by DSMB, sponsor, medical monitors, and study team prior to proceeding with enrollment of the main phase.
If there are no safety concerns, in a staggered manner, the main phase will begin enrollment of approximately 137 compounds/vaccine units (about 1500 vaccinees + about 400 under 5 years of age for parasite surveillance). Children enrolled during the pilot safety phase will join their main phase compounds/family for vaccination #3. Prior to receipt of first vaccination, all subjects will receive a full treatment course of AL. All vaccinated subjects will be monitored for safety and tolerability. Immunogenicity outcomes will be antibody responses as measured by enzyme-linked immunosorbent assay (ELISA) against recombinant Pfs230D1M. Functional activity of the induced antibodies will be assessed by standard membrane feeding assays in select samples. Vaccine activity will be measured in children 9-18 years of age who will undergo direct skin feeds (DSF) starting 2 weeks post vaccination #3 for a total of 8 DSFs.
Prior to scheduled last vaccination in members of the compound/family, children 1-4 years of age and vaccinated children 5-8 years of age will receive a full treatment course of AL prior to the expected start of the transmission season and will then be followed every 2 weeks by blood smear (BS) along with all vaccinated children. Children 9-18 years of age will also be assessed for vaccine efficacy, but as a separate analysis from those 1-8 years of age.
In Year 2, those who received vaccination during Year 1 (5 years of age and older at enrollment), if eligible and still on study, will receive a single fourth vaccination per their vaccine unit (VU) blinded arm assignment. No new individuals will be enrolled. Again, children 1-4 years of age and vaccinated children 5-8 years of age will receive a full treatment course of AL prior to the expected start of the transmission season and will then be followed every 2 weeks by BS along with all vaccinated children. Children 9-18 years of age will also be assessed for vaccine efficacy against parasitemia, but as a separate analysis from those 1-8 years of age. Immunogenicity outcomes will be antibody responses as measured by ELISA against recombinant Pfs230D1M. Functional activity of the induced antibodies will be assessed by standard membrane feeding assays in select samples. Vaccine activity will be measured in children 9-18 years of age who will undergo DSF starting 2 weeks post vaccination #4 for a total of 10 DSFs.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1301
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1b/3d HAVRIX Arm 1b (pilot) + Arm 3d (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7 Arm 1a/3c AVAXIM Arm 1a (pilot) + Arm 3c (main) to receive 40ug of Pfs230D1M-EPA/AS01 on days 0, 28, 168; receipt of artemether/lumefantrine (AL) on day -7 Arm 2b/3b HAVRIX Arm 2b (pilot) + Arm 3b (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7 and 154 Arm 3f TYPHIM Vi (Salmonella typhi vaccine) Arm 3f (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7 Arm 3e Pfs230D1M-EPA/AS01 Arm 3e (main) to receive 40microg of Pfs230D1M-EPA/AS01 on days 0, 28, 168; receipt of AL on day -7 Arm 3f HAVRIX Arm 3f (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7 Arm 1a/3c Pfs230D1M-EPA/AS01 Arm 1a (pilot) + Arm 3c (main) to receive 40ug of Pfs230D1M-EPA/AS01 on days 0, 28, 168; receipt of artemether/lumefantrine (AL) on day -7 Arm 2a/3a Pfs230D1M-EPA/AS01 Arm 2a (pilot) + Arm 3a (main) to receive 40ug of Pfs230D1M-EPA/AS01 on days 0, 28, 168; receipt of AL on day -7 and 154 Arm 1b/3d Menactra Arm 1b (pilot) + Arm 3d (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7 Arm 2b/3b Menactra Arm 2b (pilot) + Arm 3b (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7 and 154 Arm 3f Menactra Arm 3f (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7
- Primary Outcome Measures
Name Time Method Number of Participants With Local and Systemic Adverse Events in Years 1 and 2 Within 7 days after each vaccination at days, 0, 28, 126, 448 (for arms 1a, 1b, 2a, 2b), days 0, 28, 56, 392 (for arms 3a, 3b, 3c, 3d, 3e, 3f), days -14 and 385 (for arms 4a, 4b) and year 2 (for all arms) Number of participants with local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Mrtc/Usttb
🇲🇱Bamako, Mali