Trial Outcomes & Findings for Safety, Tolerability and Chemoprotective Activity of P218 in PfSPZ Challenge Model (NCT NCT03707041)
NCT ID: NCT03707041
Last Updated: 2021-04-09
Results Overview
Incidence, severity and relationship to the treatment of observed or self-reported treatment emergent adverse events (TEAEs) after two single doses of 1000 mg P218 administered 48 hours apart in healthy adult volunteers.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
9 days
Results posted on
2021-04-09
Participant Flow
The study was conducted at the SGS Life Sciences Clinical Pharmacology Unit in Antwerp.
61 subjects were screened, 32 subjects were enrolled and randomised.
Participant milestones
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 1000 mg (Oral Capsules) - Cohort 2
One administration of 1000 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 1000 mg P218 (capsules p.o.), 48 hours after first administration.
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
P218 Placebo Oral Capsules - Cohort 2
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.,) 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
P218 100 mg (Oral Capsules) - Cohort 3
One administration of 100 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 100 mg P218 (capsules p.o.), 48 hours after first administration.
P218 (100 mg) Oral Capsules: 100 mg P218 (2 x 50 mg capsules)
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
P218 Placebo Oral Capsule - Cohort 3
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
2
|
9
|
3
|
9
|
3
|
|
Overall Study
COMPLETED
|
6
|
2
|
9
|
3
|
9
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability and Chemoprotective Activity of P218 in PfSPZ Challenge Model
Baseline characteristics by cohort
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=6 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
n=2 Participants
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 1000 mg (Oral Capsules) - Cohort 2
n=9 Participants
One administration of 1000 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 1000 mg P218 (capsules p.o.), 48 hours after first administration.
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
P218 100 mg (Oral Capsules) - Cohort 3
n=9 Participants
One administration of 100 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 100 mg P218 (capsules p.o.), 48 hours after first administration.
P218 (100 mg) Oral Capsules: 100 mg P218 (2 x 50 mg capsules)
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
n=6 Participants
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
33.5 years
n=5 Participants
|
24.5 years
n=7 Participants
|
36.0 years
n=5 Participants
|
35.0 years
n=4 Participants
|
34.5 years
n=21 Participants
|
29.5 years
n=10 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
12 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
20 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
30 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Region of Enrollment
Belgium
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
9 participants
n=5 Participants
|
9 participants
n=4 Participants
|
6 participants
n=21 Participants
|
32 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: 9 daysIncidence, severity and relationship to the treatment of observed or self-reported treatment emergent adverse events (TEAEs) after two single doses of 1000 mg P218 administered 48 hours apart in healthy adult volunteers.
Outcome measures
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=6 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
n=2 Participants
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|
|
Cohort 1: Number of TEAEs
Subjects with any TEAE
|
2 Participants
|
1 Participants
|
—
|
|
Cohort 1: Number of TEAEs
Subjects without any TEAE
|
4 Participants
|
1 Participants
|
—
|
PRIMARY outcome
Timeframe: Number of days from PfSPZ Challenge DVI to positive parasitaemia, or 28 daysChemoprotective activity of two single doses of 1000 mg P218 administered 2 hours after PfSPZ Challenge and 48 hours later in healthy adult volunteers
Outcome measures
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=9 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
n=9 Participants
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
n=6 Participants
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|
|
Cohorts 2 and 3: Geometric Mean Time From PfSPZ Challenge to First Quantitative Polymerase Chain Reaction (qPCR) Outcome Equal or Greater Than 250 Asexual Parasites Per mL of Blood
|
28.000 Days
Interval 28.0 to 28.0
|
25.822 Days
Interval 22.396 to 29.771
|
10.615 Days
Interval 9.918 to 11.36
|
SECONDARY outcome
Timeframe: 35 daysIncidence, severity and relationship to the P218 treatment of observed or self-reported treatment emergent adverse events in non-immune healthy adult volunteers after two single doses of 1000 mg P218 administered 48 hours apart in a controlled human malaria infection (PfSPZ Challenge)
Outcome measures
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=9 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
n=9 Participants
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
n=6 Participants
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|
|
Cohorts 2 and 3: Number of P218 TEAEs
Any P218-related TEAEs
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Cohorts 2 and 3: Number of P218 TEAEs
No P218-related TEAEs
|
8 Participants
|
9 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: 35 daysIncidence, severity and relationship to the PfSPZ Challenge of observed or self-reported treatment emergent adverse events in non-immune healthy adult volunteers before and after P218 administration
Outcome measures
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=9 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
n=9 Participants
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
n=6 Participants
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|
|
Cohorts 2 and 3: Number of PfSPZ Challenge TEAEs
Subjects with any TEAE
|
9 Participants
|
1 Participants
|
6 Participants
|
|
Cohorts 2 and 3: Number of PfSPZ Challenge TEAEs
Subjects without any TEAE
|
0 Participants
|
8 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: On the day of positive parasitaemia or on Day 28The malaria clinical score consists of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria clinical score (maximum score possible is 42): 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. To determine severity of the 14 signs/symptoms the CTCAE grading scale grade 1 - 5 was used. Mild (1) equates to CTCAE grade 1, Moderate (2) equates to CTCAE grade 2 and Severe (3) equates to CTCAE grade 3 or above. Individual scores for each symptom as well as the total score were recorded.
Outcome measures
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=9 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
n=9 Participants
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
n=6 Participants
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|
|
Cohorts 2 and 3: Malaria Clinical Score at the Time of Introduction of Rescue Therapy
|
0.00 Malaria Clinical Score
Interval 0.0 to 0.0
|
0.00 Malaria Clinical Score
Interval 0.0 to 0.0
|
1.00 Malaria Clinical Score
Interval 0.0 to 5.0
|
SECONDARY outcome
Timeframe: 9 daysArea under the P218 plasma concentration-time curve from first administration to 48 hours after first administration
Outcome measures
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=6 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
n=9 Participants
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
n=9 Participants
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|
|
Cohorts 1, 2 and 3: P218 AUC[0-48h] - Day 1
|
16752 h*ng/mL
Standard Deviation 6958
|
13865 h*ng/mL
Standard Deviation 2663
|
1296 h*ng/mL
Standard Deviation 332
|
SECONDARY outcome
Timeframe: 9 daysArea under the P218-beta-acyl-glucuronide-OH plasma concentration-time curve from 48 hours after first P218 administration to 96 hours after first P218 administration
Outcome measures
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=6 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|
|
Cohort 1: P218-beta-acyl-glucuronide-OH AUC[48-96h]
|
27283 h*ng/mL
Standard Deviation 7106
|
—
|
—
|
SECONDARY outcome
Timeframe: 9 daysMaximum observed P218 plasma concentration after each P218 administration
Outcome measures
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=6 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
n=9 Participants
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
n=9 Participants
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|
|
Cohorts 1, 2 and 3: P218 Cmax - Day 1
|
7482 ng/mL
Standard Deviation 3889
|
7241 ng/mL
Standard Deviation 2983
|
856 ng/mL
Standard Deviation 338
|
SECONDARY outcome
Timeframe: 9 daysTime to P218 Cmax after each P218 administration
Outcome measures
| Measure |
P218 1000 mg (Oral Capsules) - Cohort 1
n=6 Participants
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo Oral Capsules - Cohort 1
n=9 Participants
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 Placebo Oral Capsule - Cohorts 2 and 3
n=9 Participants
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|
|
Cohorts 1, 2 and 3: P218 Tmax - Day 1
|
1.00 hours
Interval 1.0 to 4.0
|
1.00 hours
Interval 0.55 to 1.5
|
1.00 hours
Interval 0.5 to 2.0
|
Adverse Events
P218 1000 mg - Cohort 1
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
P218 Placebo - Cohort 1
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
P218 1000 mg - Challenge - Cohort 2
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
P218 100 mg - Challenge - Cohort 3
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
P218 Placebo - Challenge - Cohorts 2 and 3
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
P218 1000 mg - Cohort 1
n=6 participants at risk
Two administrations of 1000 mg P218 (capsules p.o.), 48 hours apart
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
|
P218 Placebo - Cohort 1
n=2 participants at risk
Two administrations of P218 placebo (capsules p.o.), 48 hours apart
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
|
P218 1000 mg - Challenge - Cohort 2
n=9 participants at risk
One administration of 1000 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 1000 mg P218 (capsules p.o.), 48 hours after first administration.
P218 (1000 mg) Oral Capsules: 1000 mg P218 (4 x 250 mg capsules)
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
P218 100 mg - Challenge - Cohort 3
n=9 participants at risk
One administration of 100 mg P218 (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of 100 mg P218 (capsules p.o.), 48 hours after first administration.
P218 (100 mg) Oral Capsules: 100 mg P218 (2 x 50 mg capsules)
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
P218 Placebo - Challenge - Cohorts 2 and 3
n=6 participants at risk
One administration of P218 placebo (capsules p.o.), 2 hours after PfSPZ Challenge and one administration of P218 placebo (capsules p.o.), 48 hours after first administration.
Placebo Oral Capsules: Placebo capsules matched to the P218 capsules with regard to appearance and taste
PfSPZ Challenge: 3200 P. falciparum Sporozoites by direct venous inoculation (DVI)
|
|---|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Skin wound
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Investigations
Transaminases increased
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
22.2%
2/9 • Number of events 3 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
General disorders
Fatigue
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
33.3%
3/9 • Number of events 4 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
General disorders
Chills
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
General disorders
Influenza-like illness
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
50.0%
3/6 • Number of events 3 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
General disorders
Malaise
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
General disorders
Vessel Puncture Site Haematoma
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Gastrointestinal disorders
diarrhoea
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Gastrointestinal disorders
Lip Dry
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Musculoskeletal and connective tissue disorders
Joint Stiffness
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
50.0%
1/2 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
44.4%
4/9 • Number of events 4 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
|
Infections and infestations
Vulvovaginal Candidiasis
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/2 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
11.1%
1/9 • Number of events 1 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/9 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
0.00%
0/6 • Adverse events were collected from time of informed consent until the last study-related activity for each subject. A maximum period of 37 days for cohort 1, and 63 days for cohorts 2 and 3.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60