Trial Outcomes & Findings for A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetic Profile of a Single Doses of MMV533. (NCT NCT04323306)

Results Overview

Assessment of adverse events (AEs) /treatment-emergent adverse events (TEAEs) (treatment phase for Part 1 and 2 defined as from IMP administration up to and including EOS).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

72 participants

Primary outcome timeframe

Safety data will be evaluated from baseline until 28 days after IMP/placebo administration

Results posted on

2024-10-17

Participant Flow

Part A: Up to 64 participants planned, 7 ascending single doses of MMV533 were planned, with up to 1 additional dose level if required. Starting dose 5 mg. Part B: 8 participants planned. The study incorporated the use of an adaptive design to allow for flexibility in the conduct of the study

Participant milestones

Participant milestones
Measure	Cohort 1 SAD 5 mg MMV533 MMV688533: Investigational medicinal product	Cohort 2 SAD 10 mg MMV533 MMV688533: Investigational medicinal product	Cohort 3 SAD 20 mg MMV533 MMV688533: Investigational medicinal product	Cohort 4 SAD 50 mg MMV533 MMV688533: Investigational medicinal product	Cohort 5 SAD 100 mg MMV533 MMV688533: Investigational medicinal product	Cohort 6 SAD 160 mg MMV533 MMV688533: Investigational medicinal product	SAD Placebos Pooled placebos	Part 2: Food Effect; MMV 533 (30mg) Fasted/Fed 4 participants were randomised and received MMV 533 (30mg) in Fasted state before cross-over to be administered 30 mg of IMP Fed state, 28 days post initial dose	Part 2: Food Effect; MMV 533 (30mg) Fed/Fasted 4 participants were randomised and received MMV 533 (30mg) in Fed state before cross-over to be administered 30 mg of IMP Fasted state, 28 days post initial dose
Overall Study STARTED	6	6	6	6	6	8	12	4	5
Overall Study COMPLETED	5	6	6	6	6	7	9	4	4
Overall Study NOT COMPLETED	1	0	0	0	0	1	3	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 SAD 5 mg MMV533 MMV688533: Investigational medicinal product	Cohort 2 SAD 10 mg MMV533 MMV688533: Investigational medicinal product	Cohort 3 SAD 20 mg MMV533 MMV688533: Investigational medicinal product	Cohort 4 SAD 50 mg MMV533 MMV688533: Investigational medicinal product	Cohort 5 SAD 100 mg MMV533 MMV688533: Investigational medicinal product	Cohort 6 SAD 160 mg MMV533 MMV688533: Investigational medicinal product	SAD Placebos Pooled placebos	Part 2: Food Effect; MMV 533 (30mg) Fasted/Fed 4 participants were randomised and received MMV 533 (30mg) in Fasted state before cross-over to be administered 30 mg of IMP Fed state, 28 days post initial dose	Part 2: Food Effect; MMV 533 (30mg) Fed/Fasted 4 participants were randomised and received MMV 533 (30mg) in Fed state before cross-over to be administered 30 mg of IMP Fasted state, 28 days post initial dose
Overall Study Physician Decision	1	0	0	0	0	0	0	0	0
Overall Study Withdrawal by Subject	0	0	0	0	0	1	3	0	1

Baseline Characteristics

A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetic Profile of a Single Doses of MMV533.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1-MMV533 5 mg n=6 Participants 6 participants were randomised and received 5 mg administered in fasting condition	Cohort 2 MMV533 10 mg n=6 Participants 6 participants were randomised and receive 10 mg in fasting condition	Cohort 3 MMV533 20 mg n=6 Participants 6 eligible participants were randomised and received 20 mg in fasting condition	Cohort 4 MMV533 50 mg n=6 Participants 6 eligible participants were randomised and received 50 mg in fasting condition	Cohort 5 MMV533 100 mg n=6 Participants 6 eligible participants were randomised and received 100 mg in fasting condition	Cohort 6 MMV533 160 mg n=8 Participants 6 eligible participants were randomised and received 160 mg in fasting condition	Placebo n=12 Participants 12 participants across 6 cohorts were randomised and received placebo administered in fasting condition	Part 2: Food Effect; MMV 533 (30mg) Fasted/Fed n=4 Participants 4 participants were randomised and received MMV 533 (30mg) in Fasted state before cross-over to be administered 30 mg of IMP Fed state, 28 days post initial dose	Part 2: Food Effect; MMV 533 (30mg) Fed/Fasted n=5 Participants 4 participants were randomised and received MMV 533 (30mg) in Fed state before cross-over to be administered 30 mg of IMP Fasted state, 28 days post initial dose	Total n=59 Participants Total of all reporting groups
Age, Continuous	26.0 years STANDARD_DEVIATION 3.34 • n=5 Participants	34.0 years STANDARD_DEVIATION 6.18 • n=7 Participants	21.5 years STANDARD_DEVIATION 5.57 • n=5 Participants	30.0 years STANDARD_DEVIATION 8.14 • n=4 Participants	23.0 years STANDARD_DEVIATION 11.69 • n=21 Participants	37.0 years STANDARD_DEVIATION 7.69 • n=10 Participants	25.5 years STANDARD_DEVIATION 8.51 • n=115 Participants	32.0 years STANDARD_DEVIATION 7.41 • n=24 Participants	28.0 years STANDARD_DEVIATION 7.33 • n=42 Participants	28.0 years STANDARD_DEVIATION 7.89 • n=42 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=10 Participants	6 Participants n=115 Participants	2 Participants n=24 Participants	2 Participants n=42 Participants	27 Participants n=42 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants	5 Participants n=10 Participants	6 Participants n=115 Participants	2 Participants n=24 Participants	3 Participants n=42 Participants	32 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	5 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	6 Participants n=21 Participants	7 Participants n=10 Participants	12 Participants n=115 Participants	4 Participants n=24 Participants	5 Participants n=42 Participants	54 Participants n=42 Participants
Ethnicity (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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	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	1 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=10 Participants	5 Participants n=115 Participants	0 Participants n=24 Participants	2 Participants n=42 Participants	17 Participants n=42 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	1 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 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	0 Participants n=115 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	5 Participants n=10 Participants	7 Participants n=115 Participants	3 Participants n=24 Participants	3 Participants n=42 Participants	39 Participants n=42 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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Body Mass Index	22.50 kg/m2 STANDARD_DEVIATION 2.176 • n=5 Participants	24.95 kg/m2 STANDARD_DEVIATION 3.144 • n=7 Participants	23.00 kg/m2 STANDARD_DEVIATION 1.218 • n=5 Participants	25.80 kg/m2 STANDARD_DEVIATION 2.769 • n=4 Participants	23.95 kg/m2 STANDARD_DEVIATION 2.737 • n=21 Participants	23.15 kg/m2 STANDARD_DEVIATION 3.261 • n=10 Participants	23.50 kg/m2 STANDARD_DEVIATION 1.969 • n=115 Participants	24.00 kg/m2 STANDARD_DEVIATION 2.598 • n=24 Participants	25.90 kg/m2 STANDARD_DEVIATION 1.503 • n=42 Participants	23.90 kg/m2 STANDARD_DEVIATION 2.413 • n=42 Participants

PRIMARY outcome

Timeframe: Safety data will be evaluated from baseline until 28 days after IMP/placebo administration

Population: Part 1: Up to 64 participants planned, 53 randomised with 50 administered IMP. All 53 analysed in Full Analysis Set (FAS), 50 (dosed) analysed in Safety Set and 38 (administered MMV533) analysed in the PK set. Part 2: 8 planned, 9 randomised and received at least one dose; 9 analysed in Safety Set. 6 participants in the PK completer subset (both periods completed, no major PDs) and 9 participants in the PK analysis subset (at least one period completed with no major PDs).

Assessment of adverse events (AEs) /treatment-emergent adverse events (TEAEs) (treatment phase for Part 1 and 2 defined as from IMP administration up to and including EOS).

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=8 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Participants with at least one TEAE	5 participants	3 participants	7 participants	4 participants	3 participants	4 participants	6 participants	5 participants	6 participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Participants with at least one IMP-related TEAE	2 participants	0 participants	1 participants	1 participants	0 participants	0 participants	1 participants	1 participants	1 participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Participants with at least one Procedure-related TEAE	2 participants	0 participants	1 participants	2 participants	2 participants	0 participants	1 participants	4 participants	0 participants

PRIMARY outcome

Timeframe: Change from baseline to 28 days post dose in Part 1 of the study and 21 days post dose in Part 2, Food effect study

Population: For Part A overall, 50 (94.3%) participants were included in the Safety Set whereas for Part B, all 9 (100%) participants were included, and no participants were excluded from the Safety Set.

Haematology: change from baseline

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=8 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Basophils	-0.02 10^9 cells/L Standard Deviation 0.04	0.03 10^9 cells/L Standard Deviation 0.05	0.00 10^9 cells/L Standard Deviation 0.00	0.00 10^9 cells/L Standard Deviation 0.00	0.03 10^9 cells/L Standard Deviation 0.05	0.00 10^9 cells/L Standard Deviation 0.06	0.01 10^9 cells/L Standard Deviation 0.05	-0.01 10^9 cells/L Standard Deviation 0.04	0.00 10^9 cells/L Standard Deviation 0.05
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Eosinophils	0.02 10^9 cells/L Standard Deviation 0.08	-0.03 10^9 cells/L Standard Deviation 0.08	0.00 10^9 cells/L Standard Deviation 0.11	-0.02 10^9 cells/L Standard Deviation 0.08	-0.02 10^9 cells/L Standard Deviation 0.08	-0.01 10^9 cells/L Standard Deviation 0.07	-0.04 10^9 cells/L Standard Deviation 0.09	-0.04 10^9 cells/L Standard Deviation 0.09	-0.03 10^9 cells/L Standard Deviation 0.05
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Lymphocytes	-0.40 10^9 cells/L Standard Deviation 0.24	-0.18 10^9 cells/L Standard Deviation 0.26	-0.28 10^9 cells/L Standard Deviation 0.15	-0.35 10^9 cells/L Standard Deviation 0.36	-0.33 10^9 cells/L Standard Deviation 0.26	-0.24 10^9 cells/L Standard Deviation 0.59	-0.18 10^9 cells/L Standard Deviation 0.35	-0.10 10^9 cells/L Standard Deviation 0.21	-3.4 10^9 cells/L Standard Deviation 0.59
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Monocytes	0.02 10^9 cells/L Standard Deviation 0.17	-0.03 10^9 cells/L Standard Deviation 0.05	0.08 10^9 cells/L Standard Deviation 0.08	-0.02 10^9 cells/L Standard Deviation 0.08	-0.08 10^9 cells/L Standard Deviation 0.08	-0.01 10^9 cells/L Standard Deviation 0.12	0.04 10^9 cells/L Standard Deviation 0.09	0.04 10^9 cells/L Standard Deviation 0.05	-0.01 10^9 cells/L Standard Deviation 0.10
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Neutrophils	0.12 10^9 cells/L Standard Deviation 1.96	-0.25 10^9 cells/L Standard Deviation 0.72	0.33 10^9 cells/L Standard Deviation 0.53	0.47 10^9 cells/L Standard Deviation 0.90	-0.97 10^9 cells/L Standard Deviation 2.29	0.23 10^9 cells/L Standard Deviation 0.44	0.09 10^9 cells/L Standard Deviation 1.88	0.14 10^9 cells/L Standard Deviation 0.75	-0.10 10^9 cells/L Standard Deviation 0.92
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Platelets	20.0 10^9 cells/L Standard Deviation 25.3	24.0 10^9 cells/L Standard Deviation 20.6	5.0 10^9 cells/L Standard Deviation 21.8	2.5 10^9 cells/L Standard Deviation 13.6	4.8 10^9 cells/L Standard Deviation 36.7	18.4 10^9 cells/L Standard Deviation 26.0	8.9 10^9 cells/L Standard Deviation 26.6	-3.3 10^9 cells/L Standard Deviation 6.2	28.3 10^9 cells/L Standard Deviation 12.6
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Leukocytes	-0.20 10^9 cells/L Standard Deviation 2.04	-0.52 10^9 cells/L Standard Deviation 0.87	0.10 10^9 cells/L Standard Deviation 0.49	0.07 10^9 cells/L Standard Deviation 1.13	-1.33 10^9 cells/L Standard Deviation 2.35	0.00 10^9 cells/L Standard Deviation 0.95	-0.12 10^9 cells/L Standard Deviation 2.07	0.03 10^9 cells/L Standard Deviation 0.90	-0.48 10^9 cells/L Standard Deviation 0.96

PRIMARY outcome

Timeframe: 24 hours to 648 hours post dose

Biochemistry: number of participants with elevated Total Bile Acids considered as Clinically significant abnormalities

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=8 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 24 hour 24 hour	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 72 hour	0 Participants	0 Participants	3 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 168 hour	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 312 hour	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 480 hour	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 648 hour	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Part 1: 28 days post IMP administration and for Part 2: 21 days post IMP administration

Urinalysis: parameters assessed: bilirubin, glucose, ketones, leucocytes, nitrite, blood, protein, urobilinogen, pH. Number of participants with clinically significant findings.

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=8 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Part 1 is 28 days post IMP and for Part 2, 21 days post IMP administration

Vital signs: respiratory rate supine and standing. Change from baseline.

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=8 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Respiratory Rate (Supine) (breaths/min)	0.0 Change in the number of breaths/minute Standard Deviation 1.6	0.0 Change in the number of breaths/minute Standard Deviation 2.2	0.0 Change in the number of breaths/minute Standard Deviation 1.5	2.0 Change in the number of breaths/minute Standard Deviation 4.1	2.0 Change in the number of breaths/minute Standard Deviation 1.5	2.0 Change in the number of breaths/minute Standard Deviation 2.5	0.0 Change in the number of breaths/minute Standard Deviation 3.2	0.0 Change in the number of breaths/minute Standard Deviation 1.8	0.0 Change in the number of breaths/minute Standard Deviation 1.7
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Respiratory Rate (Standing) (breaths/min)	0.0 Change in the number of breaths/minute Standard Deviation 1.5	0.0 Change in the number of breaths/minute Standard Deviation 4.1	0.0 Change in the number of breaths/minute Standard Deviation 1.8	2.0 Change in the number of breaths/minute Standard Deviation 2.8	1.0 Change in the number of breaths/minute Standard Deviation 2.0	2.0 Change in the number of breaths/minute Standard Deviation 2.9	0.0 Change in the number of breaths/minute Standard Deviation 3.4	2.0 Change in the number of breaths/minute Standard Deviation 2.3	2.0 Change in the number of breaths/minute Standard Deviation 1.0

PRIMARY outcome

Timeframe: Part 1 is 28 days post IMP and for Part 2, 21 days post IMP administration

Vital signs: heart rate supine and standing. Change from baseline.

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=8 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Heart Rate (beats/min)- Supine	0.5 Change in the number of beats/minute Standard Deviation 8.5	-5.0 Change in the number of beats/minute Standard Deviation 7.5	9 Change in the number of beats/minute Standard Deviation 8.7	4 Change in the number of beats/minute Standard Deviation 12.6	6 Change in the number of beats/minute Standard Deviation 11.1	0.9 Change in the number of beats/minute Standard Deviation 11.1	-1 Change in the number of beats/minute Standard Deviation 7.2	6.5 Change in the number of beats/minute Standard Deviation 8.3	4 Change in the number of beats/minute Standard Deviation 11.3
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Heart Rate (beats/min)- Standing	22 Change in the number of beats/minute Standard Deviation 13	8 Change in the number of beats/minute Standard Deviation 9.4	25 Change in the number of beats/minute Standard Deviation 13.5	16.5 Change in the number of beats/minute Standard Deviation 10.5	17.5 Change in the number of beats/minute Standard Deviation 10.3	16 Change in the number of beats/minute Standard Deviation 11.8	11.9 Change in the number of beats/minute Standard Deviation 19.5	14 Change in the number of beats/minute Standard Deviation 6	12.5 Change in the number of beats/minute Standard Deviation 13.1

PRIMARY outcome

Timeframe: Part 1: 28 days post IMP whereas for Part 2: 21 days post IMP administration

Measurements of 12-lead triplicate ECG: QTcB and QTcF interval prolongations.

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=8 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 QTcB Interval, Aggregate (ms) Prolongation >30 ms	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 QTcB Interval, Aggregate (ms)Prolongation >60 ms	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 QTcB Interval, Aggregate (ms) >450 ms	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 QTcF Interval, Aggregate (ms) Prolongation >30 ms	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 QTcF Interval, Aggregate (ms)Prolongation >60 ms	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 QTcF Interval, Aggregate (ms) >450 ms	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 24 hours to 648 hours post dose

Biochemistry: number of participants with Low Hemoglobin considered as Clinically significant abnormality

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=8 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 24 hour 24 hour	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 72 hour	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 168 hour	0 Participants	0 Participants	0 Participants	0 Participants	00 Participants	0 Participants	0 Participants	2 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 312 hour	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 480 hour	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 648 hour	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Part 1 is 28 days post IMP and for Part 2, 21 days post IMP administration

Vital signs: blood pressures, supine and standing. Change from baseline.

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=6 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Systolic Blood Pressure (mmHg)-Supine	3 mm Hg Standard Deviation 8.6	22.5 mm Hg Standard Deviation 7.5	3 mm Hg Standard Deviation 13.9	4 mm Hg Standard Deviation 6.1	2 mm Hg Standard Deviation 9.3	5 mm Hg Standard Deviation 10.6	3 mm Hg Standard Deviation 8.5	-0.5 mm Hg Standard Deviation 7.3	-2.5 mm Hg Standard Deviation 10.7
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Systolic Blood Pressure (mmHg)-Standing	4 mm Hg Standard Deviation 17	11 mm Hg Standard Deviation 10.6	-0.5 mm Hg Standard Deviation 10.7	4.5 mm Hg Standard Deviation 4.8	-4.5 mm Hg Standard Deviation 11.8	2 mm Hg Standard Deviation 13.3	1 mm Hg Standard Deviation 10	0.5 mm Hg Standard Deviation 5.9	4 mm Hg Standard Deviation 9.6
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Diastolic Blood Pressure (mmHg)- Supine	-3.5 mm Hg Standard Deviation 6	2 mm Hg Standard Deviation 7	0 mm Hg Standard Deviation 8.5	0.5 mm Hg Standard Deviation 4.7	-2 mm Hg Standard Deviation 7	2 mm Hg Standard Deviation 5.	0 mm Hg Standard Deviation 7.1	-2 mm Hg Standard Deviation 6.1	-1.5 mm Hg Standard Deviation 8.1
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Diastolic Blood Pressure (mmHg)- Standing	9.5 mm Hg Standard Deviation 5	9 mm Hg Standard Deviation 7.3	7.5 mm Hg Standard Deviation 7	-1 mm Hg Standard Deviation 5.2	5 mm Hg Standard Deviation 6.2	11.8 mm Hg Standard Deviation 9.3	5 mm Hg Standard Deviation 6.1	7.5 mm Hg Standard Deviation 7.4	7 mm Hg Standard Deviation 2.1

PRIMARY outcome

Timeframe: Part 1 is 28 days post IMP and for Part 2, 21 days post IMP administration

Vital signs: body temperature. Change from baseline.

Outcome measures

Outcome measures
Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=6 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533	0.25 Celsius degree Standard Deviation 0.56	0.5 Celsius degree Standard Deviation 0.81	0.05 Celsius degree Standard Deviation 0.36	0.35 Celsius degree Standard Deviation 0.66	-0.1 Celsius degree Standard Deviation 0.61	-0.10 Celsius degree Standard Deviation 0.39	-0.1 Celsius degree Standard Deviation 0.51	-0.1 Celsius degree Standard Deviation 0.7	0 Celsius degree Standard Deviation 0.4

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 SAD n=6 participants at risk 5 mg MMV533 with single ascending dose MMV688533: Investigational medicinal product	Cohort 2 SAD n=6 participants at risk 10 mg MMV688533: Investigational medicinal product	Cohort 3 SAD n=6 participants at risk 20 mg MMV688533: Investigational medicinal product	Cohort 4 SAD n=6 participants at risk 50 mg MMV688533: Investigational medicinal product	Cohort 5 SAD n=6 participants at risk 100 mg MMV688533: Investigational medicinal product	Cohort 6 SAD n=8 participants at risk 160 mg MMV688533: Investigational medicinal product	Part A Placebo Participants n=12 participants at risk All placebo pooled together	Part B Fasted n=8 participants at risk 30 mg Open label, 2-period cross-over, randomized, pilot food effect study to provide preliminary information on the effect of a high-fat meal on the pharmacokinetics of a single-dose oral administration of MMV533 determined to be safe in Part 1. MMV688533: Investigational medicinal product	Part B Fed n=9 participants at risk 0 mg Open label, 2-period cross-over, randomized, pilot food effect study to provide preliminary information on the effect of a high-fat meal on the pharmacokinetics of a single-dose oral administration of MMV533 determined to be safe in Part 1. MMV688533: Investigational medicinal product
Injury, poisoning and procedural complications Multiple fractures	0.00% 0/6 • AEs were collected until EOS i.e. up to Day 28 in Part A and up to Day 42 in Part B. AEs include Serious Adverse Events (SAE) and Adverse Events for Special Interest (AESI). Results from placebo are pooled together because there were no events recorded for any of the participants receiving the placebo.	0.00% 0/6 • AEs were collected until EOS i.e. up to Day 28 in Part A and up to Day 42 in Part B. AEs include Serious Adverse Events (SAE) and Adverse Events for Special Interest (AESI). Results from placebo are pooled together because there were no events recorded for any of the participants receiving the placebo.	0.00% 0/6 • AEs were collected until EOS i.e. up to Day 28 in Part A and up to Day 42 in Part B. AEs include Serious Adverse Events (SAE) and Adverse Events for Special Interest (AESI). Results from placebo are pooled together because there were no events recorded for any of the participants receiving the placebo.	0.00% 0/6 • AEs were collected until EOS i.e. up to Day 28 in Part A and up to Day 42 in Part B. AEs include Serious Adverse Events (SAE) and Adverse Events for Special Interest (AESI). Results from placebo are pooled together because there were no events recorded for any of the participants receiving the placebo.	0.00% 0/6 • AEs were collected until EOS i.e. up to Day 28 in Part A and up to Day 42 in Part B. AEs include Serious Adverse Events (SAE) and Adverse Events for Special Interest (AESI). Results from placebo are pooled together because there were no events recorded for any of the participants receiving the placebo.	12.5% 1/8 • Number of events 1 • AEs were collected until EOS i.e. up to Day 28 in Part A and up to Day 42 in Part B. AEs include Serious Adverse Events (SAE) and Adverse Events for Special Interest (AESI). Results from placebo are pooled together because there were no events recorded for any of the participants receiving the placebo.	0.00% 0/12 • AEs were collected until EOS i.e. up to Day 28 in Part A and up to Day 42 in Part B. AEs include Serious Adverse Events (SAE) and Adverse Events for Special Interest (AESI). Results from placebo are pooled together because there were no events recorded for any of the participants receiving the placebo.	0.00% 0/8 • AEs were collected until EOS i.e. up to Day 28 in Part A and up to Day 42 in Part B. AEs include Serious Adverse Events (SAE) and Adverse Events for Special Interest (AESI). Results from placebo are pooled together because there were no events recorded for any of the participants receiving the placebo.	0.00% 0/9 • AEs were collected until EOS i.e. up to Day 28 in Part A and up to Day 42 in Part B. AEs include Serious Adverse Events (SAE) and Adverse Events for Special Interest (AESI). Results from placebo are pooled together because there were no events recorded for any of the participants receiving the placebo.

Other adverse events

Adverse event data not reported

Additional Information

Benoit Bestgen

MMV

Phone: +41 79 765 18 68

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Cohort 1 SAD n=6 Participants 5 mg MMV533 6 participants were randomized to receive MMV533	Cohort 2 SAD n=6 Participants 10 mg MMV533 6 participants were randomized to receive MMV533	Cohort 3 SAD n=6 Participants 20 mg MMV533 6 participants were randomized to receive MMV533	Cohort 4 SAD n=6 Participants 50 mg MMV533 6 participants were randomized to receive MMV533	Cohort 5 SAD n=6 Participants 100 mg MMV533	Cohort 6 SAD n=8 Participants 160 mg MMV533 8 participants were randomized to receive MMV533	Placebo n=12 Participants Placebo across Cohorts 1-6	Part 2: Food Effect n=8 Participants MMV533 30mg Fasted	Part 2 - Food Effect n=9 Participants MMV533 30mg Fed
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Basophils	-0.02 10^9 cells/L Standard Deviation 0.04	0.03 10^9 cells/L Standard Deviation 0.05	0.00 10^9 cells/L Standard Deviation 0.00	0.00 10^9 cells/L Standard Deviation 0.00	0.03 10^9 cells/L Standard Deviation 0.05	0.00 10^9 cells/L Standard Deviation 0.06	0.01 10^9 cells/L Standard Deviation 0.05	-0.01 10^9 cells/L Standard Deviation 0.04	0.00 10^9 cells/L Standard Deviation 0.05
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Eosinophils	0.02 10^9 cells/L Standard Deviation 0.08	-0.03 10^9 cells/L Standard Deviation 0.08	0.00 10^9 cells/L Standard Deviation 0.11	-0.02 10^9 cells/L Standard Deviation 0.08	-0.02 10^9 cells/L Standard Deviation 0.08	-0.01 10^9 cells/L Standard Deviation 0.07	-0.04 10^9 cells/L Standard Deviation 0.09	-0.04 10^9 cells/L Standard Deviation 0.09	-0.03 10^9 cells/L Standard Deviation 0.05
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Lymphocytes	-0.40 10^9 cells/L Standard Deviation 0.24	-0.18 10^9 cells/L Standard Deviation 0.26	-0.28 10^9 cells/L Standard Deviation 0.15	-0.35 10^9 cells/L Standard Deviation 0.36	-0.33 10^9 cells/L Standard Deviation 0.26	-0.24 10^9 cells/L Standard Deviation 0.59	-0.18 10^9 cells/L Standard Deviation 0.35	-0.10 10^9 cells/L Standard Deviation 0.21	-3.4 10^9 cells/L Standard Deviation 0.59
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Monocytes	0.02 10^9 cells/L Standard Deviation 0.17	-0.03 10^9 cells/L Standard Deviation 0.05	0.08 10^9 cells/L Standard Deviation 0.08	-0.02 10^9 cells/L Standard Deviation 0.08	-0.08 10^9 cells/L Standard Deviation 0.08	-0.01 10^9 cells/L Standard Deviation 0.12	0.04 10^9 cells/L Standard Deviation 0.09	0.04 10^9 cells/L Standard Deviation 0.05	-0.01 10^9 cells/L Standard Deviation 0.10
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Neutrophils	0.12 10^9 cells/L Standard Deviation 1.96	-0.25 10^9 cells/L Standard Deviation 0.72	0.33 10^9 cells/L Standard Deviation 0.53	0.47 10^9 cells/L Standard Deviation 0.90	-0.97 10^9 cells/L Standard Deviation 2.29	0.23 10^9 cells/L Standard Deviation 0.44	0.09 10^9 cells/L Standard Deviation 1.88	0.14 10^9 cells/L Standard Deviation 0.75	-0.10 10^9 cells/L Standard Deviation 0.92
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Platelets	20.0 10^9 cells/L Standard Deviation 25.3	24.0 10^9 cells/L Standard Deviation 20.6	5.0 10^9 cells/L Standard Deviation 21.8	2.5 10^9 cells/L Standard Deviation 13.6	4.8 10^9 cells/L Standard Deviation 36.7	18.4 10^9 cells/L Standard Deviation 26.0	8.9 10^9 cells/L Standard Deviation 26.6	-3.3 10^9 cells/L Standard Deviation 6.2	28.3 10^9 cells/L Standard Deviation 12.6
The Tolerability and Safety of Ascending Single Oral Doses of MMV533 Leukocytes	-0.20 10^9 cells/L Standard Deviation 2.04	-0.52 10^9 cells/L Standard Deviation 0.87	0.10 10^9 cells/L Standard Deviation 0.49	0.07 10^9 cells/L Standard Deviation 1.13	-1.33 10^9 cells/L Standard Deviation 2.35	0.00 10^9 cells/L Standard Deviation 0.95	-0.12 10^9 cells/L Standard Deviation 2.07	0.03 10^9 cells/L Standard Deviation 0.90	-0.48 10^9 cells/L Standard Deviation 0.96