Table 3.
Overview of Adverse Events and Other Indicators and Contributors of Reactogenicity in the Challenge Phase Study Population
| Pilot PQ/CQ, n = 4 | PQ/CQ, n = 11/10a | CQ, n = 3 | Drug Control, n = 5 | Infectivity Control, n = 6 | |
|---|---|---|---|---|---|
| Challenge Phase | |||||
| Safety | |||||
| Any solicited AE | 4 (100) | 10 (91) | 3 (100) | 5 (100) | 6 (100) |
| Any SAE | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Any unsolicited AEb | 0 (0) | 10 (91) | 2 (67) | 4 (80) | 5 (83) |
| Any AE related to: | |||||
| Local mosquito bites | 4 (100) | 10 (91) | 1 (33) | 4 (80) | 5 (83) |
| Systemic mosquito bites | 0 (0) | 0 (0) | 0 (0) | 1 (20) | 0 (0) |
| Malaria | 4 (100) | 10 (91) | 3 (100) | 5 (100) | 6 (100) |
| Combination: malaria/malaria treatment | 0 (0) | 4 (36) | 2 (67) | 4 (80) | 5 (83) |
| Any laboratory abnormalities | 4 (100) | 8 (73) | 3 (100) | 4 (80) | 4 (67) |
| Any malaria related AE by grading: | |||||
| Grade 1, mild | 4 (100) | 10 (91) | 3 (100) | 5 (100) | 6 (100) |
| Grade 2, moderate | 3 (75) | 7 (64) | 2 (67) | 4 (80) | 5 (83) |
| Grade 3, severe | 1 (25) | 4 (36) | 2 (67) | 3 (60) | 3 (50) |
| Protective efficacy | |||||
| TBS+ | 4 (100) | 7 (70) | 3 (100) | 5 (100) | 6 (100) |
| Prepatent period, days, median (IQR)c | 11 (10–11) | 11 (9–undefined) | 14 (13–16) | 9 (9–11) | 9 (8–9) |
| Pre-subpatent period, days, median (IQR)d | 7 (7–7) | 7 (6–10) | 7 (7–10) | 6 (6–6) | 6.5 (6–7) |
| Symptomatic subjects at time of malaria diagnosis | 1 (25) | 4 (50) | 2 (67) | 1 (20) | 4 (67) |
| Estimated median parasite density by qRT-PCR at the time of TBS+, parasites/mL (IQR)e | 3.6 × 104 (2.0 × 104 to 4.7 × 104) | 1.1 × 104 (2.2 × 103 to 8.1 × 104) | 8.6 × 104 (2.1 × 104 to 1.1 × 105) | 4.9 × 104 (2.5 × 104 to 9.1 × 104) | 9.6 × 103 (4.6 × 103 to 2.9 × 104) |
| Estimated peak parasite density by qRT-PCR, parasites/mL | |||||
| Any positive qRT-PCR | 4 (100) | 8 (80)f | 3 (100) | 5 (100) | 6 (100) |
| Detectable to <102 | 0 (0) | 1 (10) | 0 (0) | 0 (0) | 0 (0) |
| ≥102 to <103 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| ≥103 to <104 | 0 (0) | 2 (20) | 0 (0) | 0 (0) | 1 (17) |
| ≥104 to <105 | 4 (100) | 3 (30) | 2 (67) | 3 (60) | 4 (67) |
| ≥105 | 0 (0) | 2 (20) | 1 (33) | 2 (40) | 1 (17) |
Data are the number of unique subjects (%), unless stated otherwise.
Abbreviations: +, positive; AE, adverse event; CHMI, controlled human malaria infection; CQ, chloroquine; CVac, chemoprophylaxis vaccination with sporozoites; IQR, interquartile range; PQ, primaquine; rRNA, ribosomal ribonucleic acid; qRT-PCR, qualitative real-time polymerase chain reaction; SAE, serious adverse event; TBS, thick blood smear.
aTBS/qRT-PCR data were censored for 1 PQ/CQ main phase vaccinated subject who was completely asymptomatic post-CHMI but was positive by TBS at a single time point. This subject was 18S rRNA negative at all time points post-CHMI and was TBS negative at all other time points post-CHMI, such that the positive TBS was deemed to be a false positive. The safety data were not censored (n = 11).
bUnsolicited AEs were any systemic or local symptom that was not solicited for per protocol; laboratory values were considered separately from solicited and unsolicited AEs.
cKaplan-Meier estimates of number of days from CHMI to time of first positive TBS.
dKaplan-Meier estimate of number of days from CHMI to first positive qRT-PCR count (>20 parasites/mL).
eParasite count from qRT-PCR on day of first positive TBS. Excludes the 3 PQ/CQ subjects who did not have a positive TBS following CHMI.
fA single subject in the PQ/CQ main phase arm was qRT-PCR positive at a single time point (day 10.5 post-CHMI, 58 parasites/mL), but was never TBS positive, was never qRT-PCR positive again, and was not included in the time-to-positivity analysis.