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Effectiveness of OZ439 as a Gametocytocidal and Transmission Blocking Agent (OZGAM)

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ClinicalTrials.gov Identifier: NCT02431650
Recruitment Status : Completed
First Posted : May 1, 2015
Results First Posted : May 26, 2020
Last Update Posted : May 26, 2020
Sponsor:
Collaborators:
Q-Pharm Pty Limited
Clinical Network Services (CNS) Pty Ltd
Sullivan Nicolaides Pathology
QIMR Berghofer Medical Research Institute
Army Malaria Institute, Australia
Information provided by (Responsible Party):
Medicines for Malaria Venture

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malaria
Interventions Drug: OZ439
Drug: Primaquine
Enrollment 11
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Primaquine 15mg OZ439 500mg
Hide Arm/Group Description

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.

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.

Period Title: Overall Study
Started 5 6
Completed 5 6
Not Completed 0 0
Arm/Group Title Primaquine 15mg OZ439 500mg Total
Hide Arm/Group Description

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.

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 of all reporting groups
Overall Number of Baseline Participants 5 6 11
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 6 participants 11 participants
27  (5.1) 29.2  (12.97) 28.2  (9.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 6 participants 11 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
5
 100.0%
6
 100.0%
11
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 6 participants 11 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
  16.7%
1
   9.1%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
5
 100.0%
3
  50.0%
8
  72.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
2
  33.3%
2
  18.2%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 5 participants 6 participants 11 participants
26.5  (3.68) 23.68  (2.902) 24.96  (3.434)
1.Primary Outcome
Title Infection Success of Vector Mosquitoes
Hide Description Assessing the transmissibility by oocyst detection in mosquito midgut preparations following direct and membrane (indirect) feeding.
Time Frame From day 10 to 21 post Piperaquine dosing
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Primaquine 15mg OZ439 500mg
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
2
  66.7%
3
  75.0%
2.Secondary Outcome
Title Safety: Number of AEs
Hide Description Adverse events incidence
Time Frame From Challenge inoculum on day 0 until end of study on day 31
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Primaquine 15mg OZ439 500mg
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 5 6
Measure Type: Number
Unit of Measure: Number of adverse events
17 4
Time Frame Until end of study on Day 34 (Cohort 1) or Day 36 (End of Study visit for cohorts 2a, 2b, and 3).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Primaquine 15mg OZ439 500mg
Hide Arm/Group Description

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.

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.

All-Cause Mortality
Primaquine 15mg OZ439 500mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/5 (0.00%)      0/6 (0.00%)    
Hide Serious Adverse Events
Primaquine 15mg OZ439 500mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/5 (0.00%)      0/6 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Primaquine 15mg OZ439 500mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/5 (80.00%)      2/6 (33.33%)    
Cardiac disorders     
Tachycardia *  1/5 (20.00%)  1 0/6 (0.00%)  0
Gastrointestinal disorders     
Nausea *  1/5 (20.00%)  1 0/6 (0.00%)  0
General disorders     
Fatigue *  1/5 (20.00%)  1 0/6 (0.00%)  0
Hyperhidrosis *  1/5 (20.00%)  1 0/6 (0.00%)  0
Lethargy *  1/5 (20.00%)  1 0/6 (0.00%)  0
Malaise *  1/5 (20.00%)  1 0/6 (0.00%)  0
Injury, poisoning and procedural complications     
Puncture site reaction *  2/5 (40.00%)  2 0/6 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite *  1/5 (20.00%)  1 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Metatarsalgia *  0/5 (0.00%)  0 1/6 (16.67%)  1
Myalgia *  0/5 (0.00%)  0 1/6 (16.67%)  2
Neck pain *  1/5 (20.00%)  1 0/6 (0.00%)  0
Nervous system disorders     
Dizziness *  1/5 (20.00%)  1 1/6 (16.67%)  1
Headache *  1/5 (20.00%)  1 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough *  1/5 (20.00%)  1 0/6 (0.00%)  0
Oropharyngeal pain *  1/5 (20.00%)  1 0/6 (0.00%)  0
Productive cough *  1/5 (20.00%)  1 0/6 (0.00%)  0
Sinus congestion *  1/5 (20.00%)  2 0/6 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Jörg J. Möhrle
Organization: Medicines for Malaria Venture
Phone: +41 22 555 0369
EMail: moehrlej@mmv.org
Layout table for additonal information
Responsible Party: Medicines for Malaria Venture
ClinicalTrials.gov Identifier: NCT02431650    
Other Study ID Numbers: QP15C05
First Submitted: April 17, 2015
First Posted: May 1, 2015
Results First Submitted: May 7, 2020
Results First Posted: May 26, 2020
Last Update Posted: May 26, 2020