Trial Outcomes & Findings for Study in Blood Stage Malaria Infection After DVI of Cryopreserved P. Falciparum (NF54 Strain) Sporozoites (NCT NCT04310085)
NCT ID: NCT04310085
Last Updated: 2021-09-05
Results Overview
Based on their start date(time), AEs will be allocated to the phase during which they started (Screening, Challenge, Rescue). Each AE will therefore be reported in only one phase.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Screening until end of study, day 28.
Results posted on
2021-09-05
Participant Flow
Participant milestones
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled. The target level of parasitaemia, previously achieved in healthy participants enrolled in malaria VIS at other study sites (see Section 3.2), is 5000 parasites/mL blood in Cohort 1.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet® (see Section 5.1), when the following criteria are met: Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled. The target level of parasitaemia, previously achieved in healthy participants enrolled in malaria VIS at other study sites (see Section 3.2), is 10000 parasites/mL blood in Cohort 2.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet® (see Section 5.1), when the following criteria are met: Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study in Blood Stage Malaria Infection After DVI of Cryopreserved P. Falciparum (NF54 Strain) Sporozoites
Baseline characteristics by cohort
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
41.6 years
STANDARD_DEVIATION 9.3 • n=93 Participants
|
43.1 years
STANDARD_DEVIATION 9.2 • n=4 Participants
|
42.4 years
STANDARD_DEVIATION 9.0 • n=27 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
Belgium
|
8 participants
n=93 Participants
|
8 participants
n=4 Participants
|
16 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Screening until end of study, day 28.Based on their start date(time), AEs will be allocated to the phase during which they started (Screening, Challenge, Rescue). Each AE will therefore be reported in only one phase.
Outcome measures
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Incidence and Severity of Observed or Self-reported Adverse Events (AEs) Considered PfSPZ-DVI Challenge Inoculum-related.
Adverse events
|
13 Incidence
|
12 Incidence
|
|
Incidence and Severity of Observed or Self-reported Adverse Events (AEs) Considered PfSPZ-DVI Challenge Inoculum-related.
Any grade 3 or more adverse event
|
1 Incidence
|
2 Incidence
|
|
Incidence and Severity of Observed or Self-reported Adverse Events (AEs) Considered PfSPZ-DVI Challenge Inoculum-related.
Screening Adverse events
|
0 Incidence
|
0 Incidence
|
|
Incidence and Severity of Observed or Self-reported Adverse Events (AEs) Considered PfSPZ-DVI Challenge Inoculum-related.
Challenge adverse events
|
7 Incidence
|
5 Incidence
|
|
Incidence and Severity of Observed or Self-reported Adverse Events (AEs) Considered PfSPZ-DVI Challenge Inoculum-related.
Challenge adverse events grade 3 or above
|
0 Incidence
|
0 Incidence
|
|
Incidence and Severity of Observed or Self-reported Adverse Events (AEs) Considered PfSPZ-DVI Challenge Inoculum-related.
Rescue adverse events
|
6 Incidence
|
7 Incidence
|
|
Incidence and Severity of Observed or Self-reported Adverse Events (AEs) Considered PfSPZ-DVI Challenge Inoculum-related.
Rescue adverse events grade 3 or above
|
1 Incidence
|
2 Incidence
|
PRIMARY outcome
Timeframe: Day 1 until end of study, day 28.Population: Safety set
Malaria Clinical Score 14 signs/symptoms frequently associated with malaria will be graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3): headache, myalgia (muscle ache), arthralgia (joint ache), fatigue/lethargy, malaise (general discomfort/uneasiness), chills/shivering/rigors, sweating/hot spells, anorexia, nausea, vomiting, abdominal discomfort, fever, tachycardia and hypotension. Malaria clinical score is calculated as the sum of all (14) malaria sign and symptoms scores (maximum score is 42).
Outcome measures
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Change in Malaria Clinical Score From PfSPZ-DVI Challenge Until Parasite Clearance.
|
9.63 score on a scale
Standard Deviation 7.82
|
13.0 score on a scale
Standard Deviation 1.69
|
PRIMARY outcome
Timeframe: Day 1 to day 21Population: PD analysis set: subjects from the safety analysis set with at least one available PD data who received all Riamet® doses and who experienced no major protocol deviations with relevant impact on PD data
For the purpose of this study, 'PCR positivity' is used for the 'protocol-defined PCR positivity'
Outcome measures
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Time to First PCR Positivity.
|
9.76 Days
Interval 8.58 to 11.11
|
9.60 Days
Interval 8.86 to 10.41
|
PRIMARY outcome
Timeframe: Day 1 to day 21Population: ANALYSIS set: PD
POSITIVE PARASITAEMIA IS DEFINED AS qPCR OUTCOME \>=250 PARASITES per mL BLOOD.
Outcome measures
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Parasitaemia at First PCR Positivity
|
367.2 PARASITES/mL
Interval 280.0 to 481.5
|
711.7 PARASITES/mL
Interval 405.7 to 1248.5
|
PRIMARY outcome
Timeframe: Day 1 to day 21Population: ANALYSIS SET: PD
Outcome measures
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Time to Parasitaemia of ≥5000 Parasites Per mL Blood (Cohorts 1 and 2)
|
11.19 Days
Interval 10.42 to 12.42
|
11.46 Days
Interval 10.96 to 12.42
|
PRIMARY outcome
Timeframe: Day 1 to day 21Population: ANALYSIS SET: PD
Outcome measures
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Parasitaemia at the Time Parasitaemia ≥5000 Parasites Per mL Blood (Cohorts 1 and 2)
|
12807.4 PARASITES/mL
Interval 7736.0 to 21203.4
|
18831.7 PARASITES/mL
Interval 8739.3 to 40578.9
|
PRIMARY outcome
Timeframe: Day 1 to day 21Population: ANALYSIS SET: PD
Outcome measures
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Time to First Dose of Treatment With Artemether-lumefantrine (Riamet®) (Cohorts 1 and 2)
|
12.09 Days
Interval 10.97 to 13.32
|
12.04 Days
Interval 11.46 to 12.65
|
PRIMARY outcome
Timeframe: Day 1 to day 21Population: ANALYSIS SET: PD
Outcome measures
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Parasitaemia at First Dose of Treatment With Riamet® (Cohorts 1 and 2)
|
3936.7 PARASITES/mL
Interval 218.6 to 70890.4
|
9454.3 PARASITES/mL
Interval 3662.0 to 24408.5
|
PRIMARY outcome
Timeframe: Day 1 with PfSPZ-DVI Challenge and Day 28 (per cohort).Population: ANALYSIS SET: PD
Outcome measures
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 Participants
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
Incidence of Positive PCR and Parasitaemia of ≥5000 Parasites Per mL Blood.
|
8 Participants
|
8 Participants
|
Adverse Events
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 1
n=8 participants at risk
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 1, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 5000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 1: ≥5000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
PfSPZ-DVI Challenge and Artemether Lumefantrine Cohort 2
n=8 participants at risk
8 healthy, malaria-naïve males and females, aged 18-55 years, will be enrolled per cohort; a participant may be enrolled in one cohort only. The target level of parasitaemia for cohort 2, previously achieved in healthy participants enrolled in malaria VIS at other study sites, is 10,000 parasites/mL blood.
qPCR will be performed and malaria clinical score assessed twice daily and participants will be administered registered antimalarial therapy, i.e., Riamet®, when the following criteria are met:
Cohort 2: ≥10000 parasites/mL blood or earlier if a participant has a malaria clinical score \>6 or at Investigator's discretion.
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet: artemether-lumefantrine 6 x of 4 tablets at approximately 0, 8, 24, 36, 48 and 60 h
PfSPZ-DVI Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|
|
General disorders
Influenza like illness (Flu-like Symptoms)
|
87.5%
7/8 • Number of events 10 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
100.0%
8/8 • Number of events 8 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
|
General disorders
Injection site warmth
|
0.00%
0/8 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
12.5%
1/8 • Number of events 1 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
|
Blood and lymphatic system disorders
Neutropenia
|
12.5%
1/8 • Number of events 1 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
12.5%
1/8 • Number of events 1 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
25.0%
2/8 • Number of events 2 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
12.5%
1/8 • Number of events 1 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
|
Investigations
Transaminases increased
|
0.00%
0/8 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
12.5%
1/8 • Number of events 1 • Adverse events were monitored continuously from informed consent at the Screening visit (Day -28 to Day -2) until the last study-related activity at the End Of Study Visit (Day 28).
At regular intervals during the study, participants were asked non-leading questions to determine the occurrence of any AEs. All AEs reported spontaneously during the course of the study were recorded as well.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee No announcement, oral presentation or publication relating to the Services shall be made by SGS without the prior written approval of Sponsor, except as may be otherwise required by law.
- Publication restrictions are in place
Restriction type: OTHER