Trial Outcomes & Findings for Controlled Human Malaria Infection Model for Evaluation of Transmission-blocking Interventions - Study 2 (NCT NCT03454048)
NCT ID: NCT03454048
Last Updated: 2020-07-07
Results Overview
Frequency of adverse events in the CHMI-trans model.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
24 participants
Primary outcome timeframe
up to day 51 after challenge infection
Results posted on
2020-07-07
Participant Flow
Participant milestones
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
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|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Controlled Human Malaria Infection Model for Evaluation of Transmission-blocking Interventions - Study 2
Baseline characteristics by cohort
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
24.5 years
n=93 Participants
|
22.5 years
n=4 Participants
|
25.5 years
n=27 Participants
|
20.0 years
n=483 Participants
|
24 years
n=36 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
15 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
9 Participants
n=36 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
4 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
20 Participants
n=36 Participants
|
|
Race/Ethnicity, Customized
Other/unknown
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
|
Region of Enrollment
Netherlands
|
6 participants
n=93 Participants
|
6 participants
n=4 Participants
|
6 participants
n=27 Participants
|
6 participants
n=483 Participants
|
24 participants
n=36 Participants
|
|
Hemoglobin
|
8.8 mmol/L
n=93 Participants
|
8.2 mmol/L
n=4 Participants
|
8.8 mmol/L
n=27 Participants
|
8.7 mmol/L
n=483 Participants
|
8.7 mmol/L
n=36 Participants
|
|
Body Mass Index (kg/m2)
|
22.2 Kg/m^2
n=93 Participants
|
24.2 Kg/m^2
n=4 Participants
|
20.4 Kg/m^2
n=27 Participants
|
24.7 Kg/m^2
n=483 Participants
|
22.75 Kg/m^2
n=36 Participants
|
PRIMARY outcome
Timeframe: up to day 51 after challenge infectionFrequency of adverse events in the CHMI-trans model.
Outcome measures
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
|---|---|---|---|---|
|
Frequency of Adverse Events in the CHMI-trans Model
|
95 Adverse events
|
95 Adverse events
|
107 Adverse events
|
52 Adverse events
|
PRIMARY outcome
Timeframe: up to day 51 after challenge infectionNumber of individuals in each study arm that show prevalence of gametocytes as defined by quantitative reverse-transcriptase PCR (qRT-PCR) for CCp4 (female) and PfMGET (male) mRNA with a threshold of 5 gametocytes/mL for positivity.
Outcome measures
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
|---|---|---|---|---|
|
Gametocyte Prevalence
|
5 Participants
|
6 Participants
|
6 Participants
|
6 Participants
|
PRIMARY outcome
Timeframe: up to day 51 after challenge infectionsymptoms will be ranked as (1) mild, (2) moderate, or (3) severe, depending on their intensity according to the following scale: * Mild (grade 1): awareness of symptoms that are easily tolerated and do not interfere with usual daily activity * Moderate (grade 2): discomfort that interferes with or limits usual daily activity * Severe (grade 3): disabling, with subsequent inability to perform usual daily activity, resulting in absence or required bed rest
Outcome measures
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
|---|---|---|---|---|
|
Magnitude of Adverse Events in the CHMI-trans Model
Mild (grade I)
|
64 Adverse events
|
56 Adverse events
|
86 Adverse events
|
41 Adverse events
|
|
Magnitude of Adverse Events in the CHMI-trans Model
Moderate (grade II)
|
22 Adverse events
|
22 Adverse events
|
17 Adverse events
|
8 Adverse events
|
|
Magnitude of Adverse Events in the CHMI-trans Model
Severe (grade III)
|
9 Adverse events
|
17 Adverse events
|
4 Adverse events
|
3 Adverse events
|
SECONDARY outcome
Timeframe: up to day 51 after challenge infectionPeak density of gametocytes by qRT-PCR.
Outcome measures
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
n=6 Participants
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
|---|---|---|---|---|
|
Peak Density Gametocytes
|
13.9 Gametocytes/mL
Interval 2.5 to 727.9
|
21.4 Gametocytes/mL
Interval 6.16 to 181.6
|
1442.2 Gametocytes/mL
Interval 246.6 to 3826.1
|
813.2 Gametocytes/mL
Interval 179.5 to 1617.0
|
SECONDARY outcome
Timeframe: up to day 51 after challenge infectionPopulation: Data are represented per inoculation method (Cohort A; mosquito bite infection, Cohort B; induced blood stage malaria) and not per study arm (group 1-4) as this better reflects the effects of inoculation route on induction of transmissible gametocytaemia.
The area under the curve of gametocyte density versus time. The median AUC was calculated for both cohorts. Since onset of gametocytaemia differs depending on method of infection a window of 15 days was used to calculate AUC, from the time-point where a minimum of 50% of participants within a cohort had detectable gametocytemia.
Outcome measures
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=12 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=12 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
|---|---|---|---|---|
|
AUC Gametocytes
|
99 (gametocytes*days)/mL
Interval 16.6 to 5330.0
|
11043 (gametocytes*days)/mL
Interval 1643.0 to 37326.0
|
—
|
—
|
SECONDARY outcome
Timeframe: up to day 51 after challenge infectionPopulation: Data are represented per inoculation method (Cohort A; mosquito bite infection, Cohort B; induced blood stage malaria) and not per study arm (group 1-4) as this better reflects the effects of inoculation route on induction of transmissible gametocytaemia.
The gametocyte commitment rate is estimated by dividing the peak gametocyte by the peak of asexual parasites.
Outcome measures
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=12 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=12 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
|---|---|---|---|---|
|
Gametocyte Commitment
|
0.0011 gametocytes/asexual parasite
Interval 0.0002 to 0.0141
|
0.0323 gametocytes/asexual parasite
Interval 0.0121 to 0.0891
|
—
|
—
|
SECONDARY outcome
Timeframe: up to day 51 after challenge infectionPopulation: Data are represented per inoculation method (Cohort A; mosquito bite infection, Cohort B; induced blood stage malaria) and not per study arm (group 1-4) as this better reflects the effects of inoculation route on induction of transmissible gametocytaemia.
Proportion of male gametocytes
Outcome measures
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=12 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=12 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
|---|---|---|---|---|
|
Gametocyte Sex-ratio
|
0.20 Proportion of male gametocytes
Interval 0.14 to 0.5
|
0.31 Proportion of male gametocytes
Interval 0.22 to 0.51
|
—
|
—
|
SECONDARY outcome
Timeframe: up to day 51 after challenge infectionPopulation: Data are represented per inoculation method (Cohort A; mosquito bite infection, Cohort B; induced blood stage malaria) and not per study arm (group 1-4) as this better reflects the effects of inoculation route on induction of transmissible gametocytaemia.
Prevalence of gametocyte infectiousness for Anopheles mosquitoes through Direct Feeding Assays (Direct Skin Feeding Assay, DFA).
Outcome measures
| Measure |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=12 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=12 Participants
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
|---|---|---|---|---|
|
Number of Participants Infectious for Mosquitoes Through DFA
|
0 Participants
|
9 Participants
|
—
|
—
|
Adverse Events
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
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 |
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
n=6 participants at risk
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
n=6 participants at risk
Cohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection, P. falciparum 3D7: malaria challenge infection by P. falciparum 3D7-infected mosquito bites
|
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
n=6 participants at risk
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Piperaquine (low dose): subcurative regimen (480 mg)
Piperaquine (high dose): Curative regimen (960mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
n=6 participants at risk
Cohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Piperaquine (low dose): subcurative regimen (480 mg)
Sulfadoxine pyrimethamine: Curative regimen (1000mg/50mg)
Atovaquone Proguanil: Curative regimen (1000/400 mg, for 3 days)
Blood stage malaria challenge infection, P. falciparum 3D7: P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
|
|---|---|---|---|---|
|
Infections and infestations
Fever
|
100.0%
6/6 • Number of events 16 • From inclusion until 51 days post infection
|
100.0%
6/6 • Number of events 11 • From inclusion until 51 days post infection
|
100.0%
6/6 • Number of events 13 • From inclusion until 51 days post infection
|
50.0%
3/6 • Number of events 5 • From inclusion until 51 days post infection
|
|
Infections and infestations
Headache
|
100.0%
6/6 • Number of events 27 • From inclusion until 51 days post infection
|
100.0%
6/6 • Number of events 26 • From inclusion until 51 days post infection
|
100.0%
6/6 • Number of events 33 • From inclusion until 51 days post infection
|
100.0%
6/6 • Number of events 20 • From inclusion until 51 days post infection
|
|
Infections and infestations
Nausea
|
83.3%
5/6 • Number of events 13 • From inclusion until 51 days post infection
|
66.7%
4/6 • Number of events 12 • From inclusion until 51 days post infection
|
100.0%
6/6 • Number of events 9 • From inclusion until 51 days post infection
|
50.0%
3/6 • Number of events 6 • From inclusion until 51 days post infection
|
|
Infections and infestations
Malaise
|
66.7%
4/6 • Number of events 8 • From inclusion until 51 days post infection
|
66.7%
4/6 • Number of events 15 • From inclusion until 51 days post infection
|
16.7%
1/6 • Number of events 3 • From inclusion until 51 days post infection
|
33.3%
2/6 • Number of events 2 • From inclusion until 51 days post infection
|
|
Infections and infestations
Myalgia
|
16.7%
1/6 • Number of events 1 • From inclusion until 51 days post infection
|
83.3%
5/6 • Number of events 6 • From inclusion until 51 days post infection
|
66.7%
4/6 • Number of events 7 • From inclusion until 51 days post infection
|
66.7%
4/6 • Number of events 5 • From inclusion until 51 days post infection
|
|
Infections and infestations
Fatigue
|
66.7%
4/6 • Number of events 7 • From inclusion until 51 days post infection
|
83.3%
5/6 • Number of events 13 • From inclusion until 51 days post infection
|
83.3%
5/6 • Number of events 12 • From inclusion until 51 days post infection
|
50.0%
3/6 • Number of events 6 • From inclusion until 51 days post infection
|
|
Infections and infestations
Chills
|
100.0%
6/6 • Number of events 13 • From inclusion until 51 days post infection
|
16.7%
1/6 • Number of events 2 • From inclusion until 51 days post infection
|
66.7%
4/6 • Number of events 7 • From inclusion until 51 days post infection
|
16.7%
1/6 • Number of events 2 • From inclusion until 51 days post infection
|
|
General disorders
Syncope
|
0.00%
0/6 • From inclusion until 51 days post infection
|
16.7%
1/6 • Number of events 1 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
|
Infections and infestations
Abdominal pain
|
0.00%
0/6 • From inclusion until 51 days post infection
|
33.3%
2/6 • Number of events 2 • From inclusion until 51 days post infection
|
83.3%
5/6 • Number of events 6 • From inclusion until 51 days post infection
|
33.3%
2/6 • Number of events 2 • From inclusion until 51 days post infection
|
|
Gastrointestinal disorders
Decreased appetite
|
50.0%
3/6 • Number of events 3 • From inclusion until 51 days post infection
|
33.3%
2/6 • Number of events 2 • From inclusion until 51 days post infection
|
33.3%
2/6 • Number of events 3 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
|
Infections and infestations
Dizziness
|
33.3%
2/6 • Number of events 5 • From inclusion until 51 days post infection
|
16.7%
1/6 • Number of events 3 • From inclusion until 51 days post infection
|
33.3%
2/6 • Number of events 8 • From inclusion until 51 days post infection
|
33.3%
2/6 • Number of events 4 • From inclusion until 51 days post infection
|
|
Infections and infestations
Diarrhea
|
16.7%
1/6 • Number of events 1 • From inclusion until 51 days post infection
|
16.7%
1/6 • Number of events 2 • From inclusion until 51 days post infection
|
16.7%
1/6 • Number of events 1 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
|
Infections and infestations
Palpitations
|
16.7%
1/6 • Number of events 1 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
|
Infections and infestations
Back pain
|
0.00%
0/6 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
33.3%
2/6 • Number of events 3 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
|
Infections and infestations
Arthralgia
|
0.00%
0/6 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
16.7%
1/6 • Number of events 1 • From inclusion until 51 days post infection
|
|
Cardiac disorders
Nonspecific thoracic pain
|
0.00%
0/6 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
16.7%
1/6 • Number of events 2 • From inclusion until 51 days post infection
|
0.00%
0/6 • From inclusion until 51 days post infection
|
Additional Information
Prof. dr. Teun Bousema
Radboud university medical center
Phone: +3124 3614306
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place