Trial Outcomes & Findings for Experimental Falciparum Transmission to Anopheles (NCT NCT02431637)
NCT ID: NCT02431637
Last Updated: 2020-05-26
Results Overview
Seven to ten days after blood feeding, mosquitoes will be dissected to check for oocysts in midgut preparations. For permanent preparations, oocysts will be stained with 0.1% mercurochrome in PBS for 5 to 60 mins then fixed in 1%glutaraldehyde or formaldehyde. Oocysts will be counted per mosquito dissected and recorded. Relationship between parasitemia, gametocytemia and mosquito infection (both oocyst prevalence and intensity) will be determined using generalized-linear mixed models. The number of mosquitoes dying prior to dissection will be recorded.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
6 participants
Primary outcome timeframe
7-10 days after blood feeding
Results posted on
2020-05-26
Participant Flow
Participant milestones
| Measure |
Piperaquine Phosphate After Infected Blood Malaria Challenge
Volunteers will receive a dose of 480 mg piperaquine phosphate (PQP) approx. 7 days after a challenge with P. falciparum infected red blood cells. The effects of PQP on gametocyte carriage (assessed by PCR) and infectivity to mosquitos after direct and indirect feeding on blood from volunteers will be assessed.
Administration of the malaria inoculum: Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. The threshold for commencement of treatment will be when PCR quantification of all participants is ≥ 5,000 parasites/mL.
Piperaquine Phosphate 480 mg: When PCR quantification of all participants is ≥ 5,000 parasites/mL, participants will receive a single dose of 480 mg Piperaquine Phosphate.
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|---|---|
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Overall Study
STARTED
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6
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Overall Study
COMPLETED
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6
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Experimental Falciparum Transmission to Anopheles
Baseline characteristics by cohort
| Measure |
Piperaquine Phosphate After Infected Blood Malaria Challenge
n=6 Participants
Volunteers will receive a dose of 480 mg piperaquine phosphate (PQP) approx. 7 days after a challenge with P. falciparum infected red blood cells. The effects of PQP on gametocyte carriage (assessed by PCR) and infectivity to mosquitos after direct and indirect feeding on blood from volunteers will be assessed.
Administration of the malaria inoculum: Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. The threshold for commencement of treatment will be when PCR quantification of all participants is ≥ 5,000 parasites/mL.
Piperaquine Phosphate 480 mg: When PCR quantification of all participants is ≥ 5,000 parasites/mL, participants will receive a single dose of 480 mg Piperaquine Phosphate.
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|---|---|
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Age, Continuous
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24.3 years
STANDARD_DEVIATION 4.7 • n=5 Participants
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Sex: Female, Male
Female
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4 Participants
n=5 Participants
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Sex: Female, Male
Male
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2 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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Race (NIH/OMB)
White
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6 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Body Mass Index (BMI)
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22.03 kg/m^2
STANDARD_DEVIATION 2.9 • n=5 Participants
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PRIMARY outcome
Timeframe: 7-10 days after blood feedingPopulation: Transmission prevalence was too low to evaluate the ability of the drugs to inhibit mosquito-stage parasite development using direct skin-feeding assay (DFA), direct membrane-feeding assay (DMFA), or membrane feeding assay with serum replacement (MFA SR).
Seven to ten days after blood feeding, mosquitoes will be dissected to check for oocysts in midgut preparations. For permanent preparations, oocysts will be stained with 0.1% mercurochrome in PBS for 5 to 60 mins then fixed in 1%glutaraldehyde or formaldehyde. Oocysts will be counted per mosquito dissected and recorded. Relationship between parasitemia, gametocytemia and mosquito infection (both oocyst prevalence and intensity) will be determined using generalized-linear mixed models. The number of mosquitoes dying prior to dissection will be recorded.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Blood stage Plasmodium falciparum Challenge Inoculum up to Day 31Adverse events incidence
Outcome measures
| Measure |
Piperaquine Phosphate After Infected Blood Malaria Challenge
n=6 Participants
Volunteers will receive a dose of 480 mg piperaquine phosphate (PQP) approx. 7 days after a challenge with P. falciparum infected red blood cells. The effects of PQP on gametocyte carriage (assessed by PCR) and infectivity to mosquitos after direct and indirect feeding on blood from volunteers will be assessed.
Administration of the malaria inoculum: Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. The threshold for commencement of treatment will be when PCR quantification of all participants is ≥ 5,000 parasites/mL.
Piperaquine Phosphate 480 mg: When PCR quantification of all participants is ≥ 5,000 parasites/mL, participants will receive a single dose of 480 mg Piperaquine Phosphate.
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|---|---|
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Safety: Number of AEs
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40 Number of adverse events
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Adverse Events
Piperaquine Phosphate After Infected Blood Malaria Challenge
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Piperaquine Phosphate After Infected Blood Malaria Challenge
n=6 participants at risk
Volunteers will receive a dose of 480 mg piperaquine phosphate (PQP) approx. 7 days after a challenge with P. falciparum infected red blood cells. The effects of PQP on gametocyte carriage (assessed by PCR) and infectivity to mosquitos after direct and indirect feeding on blood from volunteers will be assessed.
Administration of the malaria inoculum: Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. The threshold for commencement of treatment will be when PCR quantification of all participants is ≥ 5,000 parasites/mL.
Piperaquine Phosphate 480 mg: When PCR quantification of all participants is ≥ 5,000 parasites/mL, participants will receive a single dose of 480 mg Piperaquine Phosphate.
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|---|---|
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Blood and lymphatic system disorders
Lymphopenia
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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Gastrointestinal disorders
Nausea
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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|
Gastrointestinal disorders
Vomiting
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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General disorders
Chills
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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General disorders
Fatigue
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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General disorders
Hot flush
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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General disorders
Malaise
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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General disorders
Pyrexia
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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Injury, poisoning and procedural complications
Contusion
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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Injury, poisoning and procedural complications
Puncture site induration
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33.3%
2/6 • Number of events 3 • Overall study, up to Day 31
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Injury, poisoning and procedural complications
Puncture site reaction
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33.3%
2/6 • Number of events 3 • Overall study, up to Day 31
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Investigations
Lymphocyte count decreased
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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Metabolism and nutrition disorders
Decreased appetite
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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Musculoskeletal and connective tissue disorders
Back pain
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16.7%
1/6 • Number of events 1 • Overall study, up to Day 31
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Musculoskeletal and connective tissue disorders
Myalgia
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50.0%
3/6 • Number of events 3 • Overall study, up to Day 31
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Nervous system disorders
Headache
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66.7%
4/6 • Number of events 19 • Overall study, up to Day 31
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60