Trial Outcomes & Findings for Pyronaridine in Healthy Adult Participants Infected With Blood Stage Malaria (NCT NCT05287893)
NCT ID: NCT05287893
Last Updated: 2025-04-16
Results Overview
Maximum drug killing rate, calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan. The PKPD relationship was identified using SysFit as an Emax model with the parameters estimated from the parasitaemia data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
10 participants
Primary outcome timeframe
Day 8 to Day 50+/-2
Results posted on
2025-04-16
Participant Flow
1 participant received the IBSM inoculum on Day 0 but tested positive for covid-19 before randomisation to an IMP dose on Day 8, and received the malaria rescue medication instead. Participants were randomised to 3 possible doses in cohort 1. Following a safety and PK/PD modelling data review of cohort 1 the number of participants to receive each dose in cohort 2 was determined. Upon cohort 1 and 2 safety and PK/PD data review the endpoint could be met and cohort 3 was not required.
Participant milestones
| Measure |
Cohort 1: Pyronaridine 360 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Cohort 1: Pyronaridine 540 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Cohort 1: Pyronaridine 720 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Untreated
This inoculated participant was treated with rescue medication instead of pyronaridine due to testing positive for SARS-CoV-2 (COVID-19).
Ten (10) participants were inoculated with P. falciparum and were included in the Full Analysis Set (FAS). Nine (9) inoculated participants were subsequently administered pyronaridine, and were included in the IMP Set, PK Analysis Set, PD Analysis Set, and the PK/PD Analysis Set. Some of the 18S qPCR data for the inoculated participant who was not administered pyronaridine was used in the PD model for PK/PD analyses.
|
Cohort 2: Pyronaridine 360 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Cohort 2: Pyronaridine 540 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
|---|---|---|---|---|---|---|
|
Initial Randomization and PKPD Modelling
STARTED
|
2
|
2
|
1
|
1
|
0
|
0
|
|
Initial Randomization and PKPD Modelling
COMPLETED
|
2
|
2
|
1
|
1
|
0
|
0
|
|
Initial Randomization and PKPD Modelling
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 2 Dosing and Modelling
STARTED
|
0
|
0
|
0
|
0
|
2
|
2
|
|
Cohort 2 Dosing and Modelling
COMPLETED
|
0
|
0
|
0
|
0
|
2
|
0
|
|
Cohort 2 Dosing and Modelling
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pyronaridine in Healthy Adult Participants Infected With Blood Stage Malaria
Baseline characteristics by cohort
| Measure |
Pyronaridine 360 mg
n=4 Participants
Healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 540 mg
n=4 Participants
Healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 720 mg
n=1 Participants
Healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Untreated
n=1 Participants
This inoculated participant was treated with rescue medication instead of pyronaridine due to testing positive for SARS-CoV-2 (COVID-19).
Ten (10) participants were inoculated with P. falciparum and were included in the Full Analysis Set (FAS). Nine (9) inoculated participants were subsequently administered pyronaridine, and were included in the IMP Set, PK Analysis Set, PD Analysis Set, and the PK/PD Analysis Set. Some of the 18S qPCR data for the inoculated participant who was not administered pyronaridine was used in the PD model for PK/PD analyses.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
30.08 years
STANDARD_DEVIATION 7.46 • n=93 Participants
|
36.0 years
STANDARD_DEVIATION 14.81 • n=4 Participants
|
19.0 years
STANDARD_DEVIATION NA • n=27 Participants
|
42.0 years
STANDARD_DEVIATION NA • n=483 Participants
|
32.8 years
STANDARD_DEVIATION 11.34 • n=36 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
3 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
7 Participants
n=36 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
2 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
8 Participants
n=36 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
|
Region of Enrollment
Australia
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
10 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Day 8 to Day 50+/-2Population: The PK analysis set will include all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study treatment and experienced no protocol deviations with relevant impact on PK data. Emax is calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan, so there is only 1 Emax result.
Maximum drug killing rate, calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan. The PKPD relationship was identified using SysFit as an Emax model with the parameters estimated from the parasitaemia data.
Outcome measures
| Measure |
IBSM Challenge and Pyronaridine PK/PD Population Profile
n=10 Participants
Ten (10) participants were inoculated with P. falciparum and were included in the Full Analysis Set (FAS). Inoculation occurred on Day 0 with participants receiving approximately 2,800 viable P. falciparum-infected erythrocytes intravenously.
Day 8, nine (9) participants received pyronaridine when parasitaemia for the majority of participants was expected to be above 5,000 parasites/mL. Different doses of pyronaridine were administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments were performed and blood collected to monitor parasite clearance and pyronaridine concentration. These 9 participants received compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier, and were included in the IMP Set, PK Analysis Set, PD Analysis Set, and the PK/PD Analysis Set. One (1) inoculated participant was treated with rescue medication instead of pyronaridine due to testing positive for SARS-CoV-2 (COVID-19). Some of the 18S qPCR data for the inoculated participant who was not administered pyronaridine was used in the PD model for PK/PD analyses.
|
Pyronaridine 540 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 720 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
|---|---|---|---|
|
Emax
|
0.201 Maximum clearance rate (1/hour)
Standard Error 3.87
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 8 to Day 50+/-2Population: Full analysis set Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan. The PKPD relationship was identified using SysFit as an Emax model with the parameters estimated from the parasitaemia data.
Half Maximal Effective Concentration Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan. The PKPD relationship was identified using SysFit as an Emax model with the parameters estimated from the parasitaemia data.
Outcome measures
| Measure |
IBSM Challenge and Pyronaridine PK/PD Population Profile
n=10 Participants
Ten (10) participants were inoculated with P. falciparum and were included in the Full Analysis Set (FAS). Inoculation occurred on Day 0 with participants receiving approximately 2,800 viable P. falciparum-infected erythrocytes intravenously.
Day 8, nine (9) participants received pyronaridine when parasitaemia for the majority of participants was expected to be above 5,000 parasites/mL. Different doses of pyronaridine were administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments were performed and blood collected to monitor parasite clearance and pyronaridine concentration. These 9 participants received compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier, and were included in the IMP Set, PK Analysis Set, PD Analysis Set, and the PK/PD Analysis Set. One (1) inoculated participant was treated with rescue medication instead of pyronaridine due to testing positive for SARS-CoV-2 (COVID-19). Some of the 18S qPCR data for the inoculated participant who was not administered pyronaridine was used in the PD model for PK/PD analyses.
|
Pyronaridine 540 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 720 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
|---|---|---|---|
|
EC50
|
0.00575 μg/mL
Standard Error 11.3
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 8 to Day 50+/-2Population: Full analysis set. Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan. The PKPD relationship was identified using SysFit as an Emax model with the parameters estimated from the parasitaemia data
Hill coefficient is the slope of the drug concentration-response curve (i.e. response in this study is the parasite killing). Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan. The PKPD relationship was identified using SysFit as an Emax model with the parameters estimated from the parasitaemia data. The "Emax-model" assumes a direct effect of concentrations on parasite killing/clearance, such as: Kill = Emax x (Cc\^Hill /(Cc\^Hill + EC50\^Hill)) where Cc is the concentration in the central compartment, Emax is the maximum effect of the drug, EC50 is the concentration that results in 50% of the maximum effect, and Hill is the Hill coefficient.
Outcome measures
| Measure |
IBSM Challenge and Pyronaridine PK/PD Population Profile
n=10 Participants
Ten (10) participants were inoculated with P. falciparum and were included in the Full Analysis Set (FAS). Inoculation occurred on Day 0 with participants receiving approximately 2,800 viable P. falciparum-infected erythrocytes intravenously.
Day 8, nine (9) participants received pyronaridine when parasitaemia for the majority of participants was expected to be above 5,000 parasites/mL. Different doses of pyronaridine were administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments were performed and blood collected to monitor parasite clearance and pyronaridine concentration. These 9 participants received compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier, and were included in the IMP Set, PK Analysis Set, PD Analysis Set, and the PK/PD Analysis Set. One (1) inoculated participant was treated with rescue medication instead of pyronaridine due to testing positive for SARS-CoV-2 (COVID-19). Some of the 18S qPCR data for the inoculated participant who was not administered pyronaridine was used in the PD model for PK/PD analyses.
|
Pyronaridine 540 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 720 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
|---|---|---|---|
|
Hill Coefficient
|
6.62 Hill Coefficient
Standard Error 2.42
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 8 to Day 50+/-2Population: Full analysis set. Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan.
MIC is defined as the concentration when drug killing equals the parasite growth, i.e., the time at which the minimum parasite concentration is observed. Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan.
Outcome measures
| Measure |
IBSM Challenge and Pyronaridine PK/PD Population Profile
n=10 Participants
Ten (10) participants were inoculated with P. falciparum and were included in the Full Analysis Set (FAS). Inoculation occurred on Day 0 with participants receiving approximately 2,800 viable P. falciparum-infected erythrocytes intravenously.
Day 8, nine (9) participants received pyronaridine when parasitaemia for the majority of participants was expected to be above 5,000 parasites/mL. Different doses of pyronaridine were administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments were performed and blood collected to monitor parasite clearance and pyronaridine concentration. These 9 participants received compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier, and were included in the IMP Set, PK Analysis Set, PD Analysis Set, and the PK/PD Analysis Set. One (1) inoculated participant was treated with rescue medication instead of pyronaridine due to testing positive for SARS-CoV-2 (COVID-19). Some of the 18S qPCR data for the inoculated participant who was not administered pyronaridine was used in the PD model for PK/PD analyses.
|
Pyronaridine 540 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 720 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
|---|---|---|---|
|
Minimum Inhibitory Concentration (MIC)
|
5.5 ng/mL
Interval 4.3 to 6.9
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 8 to Day 50+/-2Population: Full analysis set. Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan.
MPC90 is defined as the concentration at which the clearance effect is at 90% of the maximum. Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan.
Outcome measures
| Measure |
IBSM Challenge and Pyronaridine PK/PD Population Profile
n=10 Participants
Ten (10) participants were inoculated with P. falciparum and were included in the Full Analysis Set (FAS). Inoculation occurred on Day 0 with participants receiving approximately 2,800 viable P. falciparum-infected erythrocytes intravenously.
Day 8, nine (9) participants received pyronaridine when parasitaemia for the majority of participants was expected to be above 5,000 parasites/mL. Different doses of pyronaridine were administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments were performed and blood collected to monitor parasite clearance and pyronaridine concentration. These 9 participants received compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier, and were included in the IMP Set, PK Analysis Set, PD Analysis Set, and the PK/PD Analysis Set. One (1) inoculated participant was treated with rescue medication instead of pyronaridine due to testing positive for SARS-CoV-2 (COVID-19). Some of the 18S qPCR data for the inoculated participant who was not administered pyronaridine was used in the PD model for PK/PD analyses.
|
Pyronaridine 540 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 720 mg
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
|---|---|---|---|
|
Minimal Parasiticidal Concentration (MPC90)
|
8 ng/mL
Interval 6.4 to 10.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 8 to Day 50+/-2Population: PK analysis set
PRR48 is defined as the parasite reduction ratio achieved within 48 hours, usually given as the reduction of values on log10 transformed scale. PRR48 provides an efficacy estimate of anti-malarial treatment and is the ratio of the parasite density over a 48 hour time-period. PRR48 is estimated using the slope of the optimal fit of the log-linear relationship of the parasitemia decay. Optimal fit is derived using the geometric mean parasitemia data (i.e. 18S qPCR measuring all blood stage malaria parasites). Optimal fit of log-linear parasitemia by time relationship is determined using left and right censoring to systematically remove potential lag phase and tail phase of parasitemia decay. The PRR48 was calculated per subject in MMV\_PYR using daily PCR data; and if the model fit was adequate for the subject (defined as overall model p-value\<0.001), the slope and corresponding standard error (SE) from the log-linear regression was used to calculate the overall dose-specific PRR48
Outcome measures
| Measure |
IBSM Challenge and Pyronaridine PK/PD Population Profile
n=4 Participants
Ten (10) participants were inoculated with P. falciparum and were included in the Full Analysis Set (FAS). Inoculation occurred on Day 0 with participants receiving approximately 2,800 viable P. falciparum-infected erythrocytes intravenously.
Day 8, nine (9) participants received pyronaridine when parasitaemia for the majority of participants was expected to be above 5,000 parasites/mL. Different doses of pyronaridine were administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments were performed and blood collected to monitor parasite clearance and pyronaridine concentration. These 9 participants received compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier, and were included in the IMP Set, PK Analysis Set, PD Analysis Set, and the PK/PD Analysis Set. One (1) inoculated participant was treated with rescue medication instead of pyronaridine due to testing positive for SARS-CoV-2 (COVID-19). Some of the 18S qPCR data for the inoculated participant who was not administered pyronaridine was used in the PD model for PK/PD analyses.
|
Pyronaridine 540 mg
n=4 Participants
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 720 mg
n=1 Participants
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
|---|---|---|---|
|
Parasite Reduction Ratio in 48 h (log10PRR48)
|
2.58 log[(parasites/mL)/hour]
Interval 2.43 to 2.74
|
2.53 log[(parasites/mL)/hour]
Interval 2.37 to 2.68
|
2.85 log[(parasites/mL)/hour]
Interval 2.65 to 3.06
|
Adverse Events
Pyronaridine 360 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Pyronaridine 540 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Pyronaridine 720 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Pyronaridine 360 mg
n=4 participants at risk
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 540 mg
n=4 participants at risk
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
Pyronaridine 720 mg
n=1 participants at risk
Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes.
Day 8 participants will be dosed with pyronaridine when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration.
Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2, or earlier.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Gastrointestinal disorders
Nausea
|
50.0%
2/4 • Number of events 2 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 2 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
General disorders
Administration site discomfort
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
General disorders
Chills
|
25.0%
1/4 • Number of events 3 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
General disorders
Fatigue
|
50.0%
2/4 • Number of events 3 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
75.0%
3/4 • Number of events 4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 2 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
General disorders
Feeling hot
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
General disorders
Feeling of body temperature change
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
General disorders
Malaise
|
25.0%
1/4 • Number of events 3 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
50.0%
2/4 • Number of events 3 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
General disorders
Pyrexia
|
25.0%
1/4 • Number of events 4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
75.0%
3/4 • Number of events 4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 5 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Infections and infestations
Covid-19
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Infections and infestations
Lower respiratory tract infection
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Investigations
Haemoglobin decreased
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 2 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 2 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
50.0%
2/4 • Number of events 3 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
50.0%
2/4 • Number of events 2 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
25.0%
1/4 • Number of events 2 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Nervous system disorders
Headache
|
75.0%
3/4 • Number of events 17 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
50.0%
2/4 • Number of events 12 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 5 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
100.0%
1/1 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
50.0%
2/4 • Number of events 2 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
|
Vascular disorders
Flushing
|
0.00%
0/4 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
25.0%
1/4 • Number of events 1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
0.00%
0/1 • The period of observation for collection of AEs extends from the time of inoculation with the malaria challenge agent (Day 0) to EOS (Day 50+/-2). A total maximum of 53 days.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PI's organisation will prepare the manuscript once the Clinical Study Report finalisation (within 12 months of trial completion). The Sponsor organisation will have 45 days to review prior to submission for for publication.
- Publication restrictions are in place
Restriction type: OTHER