Trial Outcomes & Findings for DSM265 Chemoprophylaxis of Plasmodium Falciparum Malaria (NCT NCT02450578)
NCT ID: NCT02450578
Last Updated: 2021-01-13
Results Overview
The infection rate is the number (percentage) of subjects in a cohort who became positive for parasitemia. Complete protection = Subjects with pre-patent period equal to 28 days.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
22 participants
Primary outcome timeframe
Day 0 to Day 28 post-inoculum (daily)
Results posted on
2021-01-13
Participant Flow
A total of 40 subjects were screened. Of these 22 (55.0%) were enrolled to participate in the study
One subject was allocated to treatment but did not receive any study medication due to an ECG abnormality discovered after randomization and, therefore, 21 out of 22 subjects received at least one dose of the study medications. In agreement with the Safety Review Team, the Sponsor decided to close the study without progressing to conduct Cohort 3.
Participant milestones
| Measure |
Cohort 1A: 400 mg DSM265, Sporozoite Challenge
DSM265 400mg on Day -1, sporozoite challenge on Day 0
DSM265 400mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265, Sporozoite Challenge
DSM265 400mg on Day -7, sporozoite challenge on Day 0
DSM265 400mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2, Sporozoite Challenge
Placebo to DSM265 400 mg on Day -1, sporozoite challenge on Day 0
Placebo: Single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
4
|
|
Overall Study
COMPLETED
|
5
|
6
|
6
|
4
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1A: 400 mg DSM265, Sporozoite Challenge
DSM265 400mg on Day -1, sporozoite challenge on Day 0
DSM265 400mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265, Sporozoite Challenge
DSM265 400mg on Day -7, sporozoite challenge on Day 0
DSM265 400mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2, Sporozoite Challenge
Placebo to DSM265 400 mg on Day -1, sporozoite challenge on Day 0
Placebo: Single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
Overall Study
ECG abnormality so not treated
|
1
|
0
|
0
|
0
|
Baseline Characteristics
DSM265 Chemoprophylaxis of Plasmodium Falciparum Malaria
Baseline characteristics by cohort
| Measure |
Placebo Cohorts 1A and 2
n=4 Participants
Placebo to DSM265 400 mg on Day -7, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1A: 400 mg DSM265, Sporozoite Challenge
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265, Sporozoite Challenge
n=6 Participants
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
Age (years)
|
24.82 years
STANDARD_DEVIATION 3.95 • n=483 Participants
|
24.20 years
STANDARD_DEVIATION 4.02 • n=93 Participants
|
26.67 years
STANDARD_DEVIATION 4.93 • n=4 Participants
|
25.33 years
STANDARD_DEVIATION 4.18 • n=27 Participants
|
26.00 years
STANDARD_DEVIATION 4.24 • n=36 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=483 Participants
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
8 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=483 Participants
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
13 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=483 Participants
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=483 Participants
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=483 Participants
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=483 Participants
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=483 Participants
|
5 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
21 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=483 Participants
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=483 Participants
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=36 Participants
|
|
Region of Enrollment
Germany
|
4 participants
n=483 Participants
|
5 participants
n=93 Participants
|
6 participants
n=4 Participants
|
6 participants
n=27 Participants
|
21 participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Day 0 to Day 28 post-inoculum (daily)Population: All subjects who received both at least one dose of study medication and the PfSPZ challenge
The infection rate is the number (percentage) of subjects in a cohort who became positive for parasitemia. Complete protection = Subjects with pre-patent period equal to 28 days.
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
n=6 Participants
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
n=4 Participants
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
Infection Rate
Complete Protection
|
5 Participants
|
6 Participants
|
3 Participants
|
0 Participants
|
|
Infection Rate
Parasitemic
|
0 Participants
|
0 Participants
|
3 Participants
|
4 Participants
|
PRIMARY outcome
Timeframe: Day 0 to Day 28 post-inoculum (daily)Population: All subjects who received both at least one dose of study medication and the PfSPZ challenge
The pre-patent period is defined as the time (days) from inoculation with PfSPZ to first occurrence of a positive TBS. If no positive TBS is seen by Day 28, this variable is set to 28 days. Complete protection = Subjects showing with pre-patent period equal to 28 days.
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
n=6 Participants
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
n=4 Participants
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
Pre-patent Period
|
28.0 Days
Geometric Coefficient of Variation 0.00
|
28.0 Days
Geometric Coefficient of Variation 0.00
|
20.6 Days
Geometric Coefficient of Variation 2.78
|
11.7 Days
Geometric Coefficient of Variation 7.93
|
SECONDARY outcome
Timeframe: From first dose (Day -1 in Cohort 1A and Day -7 in Cohort 2) to Day 60 post-inoculumPopulation: All the subjects included in the safety population were administered the study medication.
Safety \& tolerability of DSM265 for causal and suppressive chemoprophylaxis in non-immune healthy volunteers in a non-immune healthy volunteers in CHMI with PfSPZ challenge.
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events as a Measure of Safety & Tolerability of DSM265
|
5 Participants
|
6 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From first dose (Day -1, Cohort 1b) to Day 60 post-inoculumPopulation: All the subjects included in the safety population were administered the study medication.
Safety \& tolerability of Malarone for causal and suppressive chemoprophylaxis in non-immune healthy volunteers in a Plasmodium falciparum sporozoite challenge. Measured by adverse events, laboratory data. Malarone® was administered as a single daily dose over a period of 9 days from Day -1 to Day 7.
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=6 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE) as a Measure of Safety & Tolerability of Malarone
|
5 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 0 to Day 60 post-inoculumPopulation: All the subjects included in the safety population were administered the study medication.
Safety \& tolerability of Plasmodium falciparum sporozoite challenge inoculum during DSM265 administration, and Malarone administration. Measured by adverse events, laboratory data
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
n=6 Participants
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
n=4 Participants
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Plasmodium Falciparum Sporozoite Challenge Inoculum
|
3 Participants
|
5 Participants
|
5 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculumPopulation: All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set).
Pre-dose and post-dose during the period including Day 28
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
DSM265 Pharmacokinetics Profile - T Max
T max DBS
|
2.02 hours
Interval 1.0 to 14.0
|
8.48 hours
Interval 0.5 to 14.0
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - T Max
T max Plasma
|
2.00 hours
Interval 1.0 to 4.02
|
8.48 hours
Interval 0.5 to 14.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculumPopulation: All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set).
Pre-dose and post-dose during the period including Day 28
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
DSM265 Pharmacokinetics Profile - T 1/2
t 1/2 DBS
|
132 hours
Geometric Coefficient of Variation 31.4
|
113 hours
Geometric Coefficient of Variation 39.0
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - T 1/2
t 1/2 Plasma
|
134 hours
Geometric Coefficient of Variation 34.8
|
116 hours
Geometric Coefficient of Variation 40.4
|
—
|
—
|
SECONDARY outcome
Timeframe: From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculumPopulation: All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set).
Pre-dose and post-dose during the period including Day 28
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
DSM265 Pharmacokinetics Profile - C Max
C max DBS
|
6860 ng/mL
Geometric Coefficient of Variation 28.2
|
6990 ng/mL
Geometric Coefficient of Variation 15.0
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - C Max
C max Plasma
|
13300 ng/mL
Geometric Coefficient of Variation 34.3
|
11200 ng/mL
Geometric Coefficient of Variation 18.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculumPopulation: All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set).
Pre-dose and post-dose during the period including Day 28 for AUC 0-∞, AUC 0-168h, and AUC 0-480h
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h
AUC 0-∞ DBS
|
979000 ng*h/mL
Geometric Coefficient of Variation 25.8
|
906000 ng*h/mL
Geometric Coefficient of Variation 29.8
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h
AUC 0-∞ Plasma
|
1870000 ng*h/mL
Geometric Coefficient of Variation 23.4
|
1540000 ng*h/mL
Geometric Coefficient of Variation 30.4
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h
AUC 0-168h DBS
|
582000 ng*h/mL
Geometric Coefficient of Variation 22.8
|
568000 ng*h/mL
Geometric Coefficient of Variation 13.3
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h
AUC 0-168h Plasma
|
1100000 ng*h/mL
Geometric Coefficient of Variation 22.3
|
949000 ng*h/mL
Geometric Coefficient of Variation 14.0
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h
AUC 0-480h DBS
|
863000 ng*h/mL
Geometric Coefficient of Variation 22.0
|
847000 ng*h/mL
Geometric Coefficient of Variation 25.4
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h
AUC 0-480h Plasma
|
1680000 ng*h/mL
Geometric Coefficient of Variation 19.5
|
1430000 ng*h/mL
Geometric Coefficient of Variation 25.9
|
—
|
—
|
SECONDARY outcome
Timeframe: From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculumPopulation: All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set).
Pre-dose and post-dose during the period including Day 28
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
DSM265 Pharmacokinetics Profile - CL/F
CL/F DBS
|
409 mL/h
Geometric Coefficient of Variation 25.8
|
441 mL/h
Geometric Coefficient of Variation 29.8
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - CL/F
CL/F Plasma
|
214 mL/h
Geometric Coefficient of Variation 23.4
|
260 mL/h
Geometric Coefficient of Variation 30.4
|
—
|
—
|
SECONDARY outcome
Timeframe: From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculumPopulation: All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set).
Pre-dose and post-dose during the period including Day 28
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
DSM265 Pharmacokinetics Profile - Vz/F
Vz/F DBS
|
77900 mL
Geometric Coefficient of Variation 29.0
|
71700 mL
Geometric Coefficient of Variation 18.7
|
—
|
—
|
|
DSM265 Pharmacokinetics Profile - Vz/F
Vz/F Plasma
|
41400 mL
Geometric Coefficient of Variation 31.8
|
43600 mL
Geometric Coefficient of Variation 18.9
|
—
|
—
|
SECONDARY outcome
Timeframe: From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculumPopulation: All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set).
Pre-dose and post-dose during the period including Day 28
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
DSM450 Pharmacokinetics Profile - T Max
t max DBS
|
169 hours
Interval 71.9 to 265.0
|
216 hours
Interval 48.3 to 267.0
|
—
|
—
|
|
DSM450 Pharmacokinetics Profile - T Max
t max Plasma
|
169 hours
Interval 71.9 to 265.0
|
169 hours
Interval 72.4 to 266.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculumPopulation: All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set).
Pre-dose and post-dose during the period including Day 28
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
DSM450 Pharmacokinetics Profile - Cmax
Cmax DBS
|
545 ng/mL
Geometric Coefficient of Variation 35.3
|
714 ng/mL
Geometric Coefficient of Variation 37.1
|
—
|
—
|
|
DSM450 Pharmacokinetics Profile - Cmax
Cmax Plasma
|
999 ng/mL
Geometric Coefficient of Variation 31.0
|
1170 ng/mL
Geometric Coefficient of Variation 36.7
|
—
|
—
|
SECONDARY outcome
Timeframe: From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculumPopulation: All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set).
Pre-dose and post-dose during the period including Day 28 for AUC 0-t, AUC 0-168h, and AUC 0-480h
Outcome measures
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 Participants
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 Participants
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h
AUC 0-480h DBS
|
185000 ng*h/mL
Geometric Coefficient of Variation 34.9
|
234000 ng*h/mL
Geometric Coefficient of Variation 46.5
|
—
|
—
|
|
DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h
AUC 0-480h Plasma
|
326000 ng*h/mL
Geometric Coefficient of Variation 32.1
|
375000 ng*h/mL
Geometric Coefficient of Variation 44.1
|
—
|
—
|
|
DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h
AUC 0-∞ DBS
|
185000 ng*h/mL
Geometric Coefficient of Variation 34.9
|
225000 ng*h/mL
Geometric Coefficient of Variation 42.5
|
—
|
—
|
|
DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h
AUC 0-∞ Plasma
|
326000 ng*h/mL
Geometric Coefficient of Variation 32.1
|
367000 ng*h/mL
Geometric Coefficient of Variation 39.7
|
—
|
—
|
|
DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h
AUC 0-168h DBS
|
63800 ng*h/mL
Geometric Coefficient of Variation 44.9
|
85300 ng*h/mL
Geometric Coefficient of Variation 45.1
|
—
|
—
|
|
DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h
AUC 0-168h Plasma
|
115000 ng*h/mL
Geometric Coefficient of Variation 45.9
|
142000 ng*h/mL
Geometric Coefficient of Variation 40.4
|
—
|
—
|
SECONDARY outcome
Timeframe: From first dose of DSM265 (Day -1 in Cohort 1a, Day -7 in Cohort 2 and Day -X in Cohort 3) to 480 hours post-dosePopulation: Data were not collected. Analysis was not done because, because all subjects were administered with the same dose of 400mg DSM; so not enough variability for the "DSM concentration" parameter.
The profile of plasma concentrations and pharmacokinetic parameters (AUC, Cmax, Tmax, T0-inf, AUC0-t, t1/2) will be reviewed on a background of the safety profile (adverse events, laboratory and ECG data) and the clearance of Plasmodium falciparum parasites (efficacy) after administration of the sporozoite challenge
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 6 post-inoculum to Day 60Population: Recrudescence was not observed in this study.
On any re-appearance of parasites, thick smears and PCR samples will be examined to determine whether the parasite is a different variant(recrudescence) or has the same genetic profile as the original infection (re-infection) post-dose
Outcome measures
Outcome data not reported
Adverse Events
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Cohort 1B: Malarone, Sporozoite Challenge
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Placebo Cohorts 1A and 2
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 participants at risk
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 participants at risk
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
n=6 participants at risk
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
n=4 participants at risk
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
Vascular disorders
Pulmonary embolism
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
Other adverse events
| Measure |
Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0)
n=5 participants at risk
DSM265 400 mg on Day -1, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 1B: Malarone, Sporozoite Challenge
n=6 participants at risk
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0
Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0)
n=6 participants at risk
DSM265 400 mg on Day -7, sporozoite challenge on Day 0
DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
Placebo Cohorts 1A and 2
n=4 participants at risk
Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0
Placebo to DSM265 400 mg: single oral administration in a fed state
Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation
|
|---|---|---|---|---|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
33.3%
2/6 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
66.7%
4/6 • Number of events 4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
50.0%
2/4 • Number of events 3 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
50.0%
2/4 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
General disorders
Chills
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
50.0%
3/6 • Number of events 3 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
50.0%
2/4 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
General disorders
Fatigue
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
100.0%
6/6 • Number of events 10 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
100.0%
4/4 • Number of events 7 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
General disorders
Pyrexia
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
50.0%
3/6 • Number of events 8 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
50.0%
2/4 • Number of events 6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Nervous system disorders
Dizziness
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
75.0%
3/4 • Number of events 4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Nervous system disorders
Headache
|
20.0%
1/5 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
83.3%
5/6 • Number of events 11 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
100.0%
4/4 • Number of events 11 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
50.0%
2/4 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Infections and infestations
Sinusitis
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
33.3%
2/6 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Infections and infestations
Viral upper respiratory tract infection
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
33.3%
2/6 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
33.3%
2/6 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
33.3%
2/6 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Blood and lymphatic system disorders
Haemolysis
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
33.3%
2/6 • Number of events 3 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Cardiac disorders
Palpitations
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
25.0%
1/4 • Number of events 4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/6 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
66.7%
4/6 • Number of events 5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
50.0%
2/4 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
33.3%
2/6 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
0.00%
0/4 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/5 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
16.7%
1/6 • Number of events 2 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
50.0%
3/6 • Number of events 3 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
25.0%
1/4 • Number of events 1 • Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place