Trial Outcomes & Findings for Effectiveness of OZ439 as a Gametocytocidal and Transmission Blocking Agent (NCT NCT02431650)

Last Updated: 2020-05-26

Results Overview

Assessing the transmissibility by oocyst detection in mosquito midgut preparations following direct and membrane (indirect) feeding.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

11 participants

Primary outcome timeframe

From day 10 to 21 post Piperaquine dosing

Results posted on

2020-05-26

Participant Flow

Participant milestones

Participant milestones
Measure	Primaquine 15mg Administration of Primaquine 15mg (control). Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants of this arm will receive 15mg of Primaquine treatment as the control.	OZ439 500mg Administration of OZ439 500mg. Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants will receive 500mg of OZ439.
Overall Study STARTED	5	6
Overall Study COMPLETED	5	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effectiveness of OZ439 as a Gametocytocidal and Transmission Blocking Agent

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Primaquine 15mg n=5 Participants Administration of Primaquine 15mg (control). Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants of this arm will receive 15mg of Primaquine treatment as the control.	OZ439 500mg n=6 Participants Administration of OZ439 500mg. Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants will receive 500mg of OZ439.	Total n=11 Participants Total of all reporting groups
Age, Continuous	27 years STANDARD_DEVIATION 5.1 • n=93 Participants	29.2 years STANDARD_DEVIATION 12.97 • n=4 Participants	28.2 years STANDARD_DEVIATION 9.79 • n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	6 Participants n=4 Participants	11 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	5 Participants n=93 Participants	3 Participants n=4 Participants	8 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Body Mass Index (BMI)	26.5 kg/m^2 STANDARD_DEVIATION 3.68 • n=93 Participants	23.68 kg/m^2 STANDARD_DEVIATION 2.902 • n=4 Participants	24.96 kg/m^2 STANDARD_DEVIATION 3.434 • n=27 Participants

PRIMARY outcome

Timeframe: From day 10 to 21 post Piperaquine dosing

Population: Transmission of gametocytes to mosquitos was only determined for 7 of the 11 subjects that participated in the trial. Transmission of gametocytes to mosquitoes was observed in 5 of the 7 subjects analysed.

Assessing the transmissibility by oocyst detection in mosquito midgut preparations following direct and membrane (indirect) feeding.

Outcome measures

Outcome measures
Measure	Primaquine 15mg n=3 Participants Administration of Primaquine 15mg (control). Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants of this arm will receive 15mg of Primaquine treatment as the control.	OZ439 500mg n=4 Participants Administration of OZ439 500mg. Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants will receive 500mg of OZ439.
Infection Success of Vector Mosquitoes	2 Participants	3 Participants

SECONDARY outcome

Timeframe: From Challenge inoculum on day 0 until end of study on day 31

Adverse events incidence

Outcome measures

Outcome measures
Measure	Primaquine 15mg n=5 Participants Administration of Primaquine 15mg (control). Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants of this arm will receive 15mg of Primaquine treatment as the control.	OZ439 500mg n=6 Participants Administration of OZ439 500mg. Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants will receive 500mg of OZ439.
Safety: Number of AEs	17 Number of adverse events	4 Number of adverse events

Adverse Events

Primaquine 15mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

OZ439 500mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Jörg J. Möhrle

Medicines for Malaria Venture

Phone: +41 22 555 0369

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Primaquine 15mg n=5 participants at risk Administration of Primaquine 15mg (control). Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants of this arm will receive 15mg of Primaquine treatment as the control.	OZ439 500mg n=6 participants at risk Administration of OZ439 500mg. Each participant in the cohort will be inoculated on Day 0 with \~2,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. When PCR quantification of all participants is ≥ 5,000 parasites/mL, they will receive a single dose of 480 mg of piperaquine phosphate to clear blood stage parasitemia. When gametocytemia is at the peak (approximately 15 days after administration of piperaquine), participants will receive 500mg of OZ439.
Cardiac disorders Tachycardia	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Gastrointestinal disorders Nausea	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
General disorders Fatigue	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
General disorders Hyperhidrosis	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
General disorders Lethargy	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
General disorders Malaise	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Injury, poisoning and procedural complications Puncture site reaction	40.0% 2/5 • Number of events 2 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Metabolism and nutrition disorders Decreased appetite	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Musculoskeletal and connective tissue disorders Metatarsalgia	0.00% 0/5 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	16.7% 1/6 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/5 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	16.7% 1/6 • Number of events 2 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Musculoskeletal and connective tissue disorders Neck pain	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Nervous system disorders Dizziness	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	16.7% 1/6 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Nervous system disorders Headache	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Respiratory, thoracic and mediastinal disorders Cough	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Respiratory, thoracic and mediastinal disorders Productive cough	20.0% 1/5 • Number of events 1 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Respiratory, thoracic and mediastinal disorders Sinus congestion	20.0% 1/5 • Number of events 2 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).	0.00% 0/6 • Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).