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Experimental Falciparum Transmission to Anopheles (EFITA)

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ClinicalTrials.gov Identifier: NCT02431637
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: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malaria
Interventions Biological: Administration of the malaria inoculum
Drug: Piperaquine Phosphate 480 mg
Enrollment 6
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Piperaquine Phosphate After Infected Blood Malaria Challenge
Hide Arm/Group Description

Volunteers will receive a dose of 480 mg piperaquine phosphate (PQP) approx. 7 days after a challenge with P. falciparum infected red blood cells. The effects of PQP on gametocyte carriage (assessed by PCR) and infectivity to mosquitos after direct and indirect feeding on blood from volunteers will be assessed.

Administration of the malaria inoculum: 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. The threshold for commencement of treatment will be when PCR quantification of all participants is ≥ 5,000 parasites/mL.

Piperaquine Phosphate 480 mg: When PCR quantification of all participants is ≥ 5,000 parasites/mL, participants will receive a single dose of 480 mg Piperaquine Phosphate.

Period Title: Overall Study
Started 6
Completed 6
Not Completed 0
Arm/Group Title Piperaquine Phosphate After Infected Blood Malaria Challenge
Hide Arm/Group Description

Volunteers will receive a dose of 480 mg piperaquine phosphate (PQP) approx. 7 days after a challenge with P. falciparum infected red blood cells. The effects of PQP on gametocyte carriage (assessed by PCR) and infectivity to mosquitos after direct and indirect feeding on blood from volunteers will be assessed.

Administration of the malaria inoculum: 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. The threshold for commencement of treatment will be when PCR quantification of all participants is ≥ 5,000 parasites/mL.

Piperaquine Phosphate 480 mg: When PCR quantification of all participants is ≥ 5,000 parasites/mL, participants will receive a single dose of 480 mg Piperaquine Phosphate.

Overall Number of Baseline Participants 6
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants
24.3  (4.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
Female
4
  66.7%
Male
2
  33.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
6
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 6 participants
22.03  (2.9)
1.Primary Outcome
Title Successful Infection of Vector Mosquitoes Following Both Direct and Indirect Feeding on the Blood of Infected Participants
Hide Description Seven to ten days after blood feeding, mosquitoes will be dissected to check for oocysts in midgut preparations. For permanent preparations, oocysts will be stained with 0.1% mercurochrome in PBS for 5 to 60 mins then fixed in 1%glutaraldehyde or formaldehyde. Oocysts will be counted per mosquito dissected and recorded. Relationship between parasitemia, gametocytemia and mosquito infection (both oocyst prevalence and intensity) will be determined using generalized-linear mixed models. The number of mosquitoes dying prior to dissection will be recorded.
Time Frame 7-10 days after blood feeding
Hide Outcome Measure Data
Hide Analysis Population Description
Transmission prevalence was too low to evaluate the ability of the drugs to inhibit mosquito-stage parasite development using direct skin-feeding assay (DFA), direct membrane-feeding assay (DMFA), or membrane feeding assay with serum replacement (MFA SR).
Arm/Group Title Piperaquine Phosphate After Infected Blood Malaria Challenge
Hide Arm/Group Description:

Volunteers will receive a dose of 480 mg piperaquine phosphate (PQP) approx. 7 days after a challenge with P. falciparum infected red blood cells. The effects of PQP on gametocyte carriage (assessed by PCR) and infectivity to mosquitos after direct and indirect feeding on blood from volunteers will be assessed.

Administration of the malaria inoculum: 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. The threshold for commencement of treatment will be when PCR quantification of all participants is ≥ 5,000 parasites/mL.

Piperaquine Phosphate 480 mg: When PCR quantification of all participants is ≥ 5,000 parasites/mL, participants will receive a single dose of 480 mg Piperaquine Phosphate.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Safety: Number of AEs
Hide Description Adverse events incidence
Time Frame Blood stage Plasmodium falciparum Challenge Inoculum up to Day 31
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Piperaquine Phosphate After Infected Blood Malaria Challenge
Hide Arm/Group Description:

Volunteers will receive a dose of 480 mg piperaquine phosphate (PQP) approx. 7 days after a challenge with P. falciparum infected red blood cells. The effects of PQP on gametocyte carriage (assessed by PCR) and infectivity to mosquitos after direct and indirect feeding on blood from volunteers will be assessed.

Administration of the malaria inoculum: 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. The threshold for commencement of treatment will be when PCR quantification of all participants is ≥ 5,000 parasites/mL.

Piperaquine Phosphate 480 mg: When PCR quantification of all participants is ≥ 5,000 parasites/mL, participants will receive a single dose of 480 mg Piperaquine Phosphate.

Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Number of adverse events
40
Time Frame Overall study, up to Day 31
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Piperaquine Phosphate After Infected Blood Malaria Challenge
Hide Arm/Group Description

Volunteers will receive a dose of 480 mg piperaquine phosphate (PQP) approx. 7 days after a challenge with P. falciparum infected red blood cells. The effects of PQP on gametocyte carriage (assessed by PCR) and infectivity to mosquitos after direct and indirect feeding on blood from volunteers will be assessed.

Administration of the malaria inoculum: 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. The threshold for commencement of treatment will be when PCR quantification of all participants is ≥ 5,000 parasites/mL.

Piperaquine Phosphate 480 mg: When PCR quantification of all participants is ≥ 5,000 parasites/mL, participants will receive a single dose of 480 mg Piperaquine Phosphate.

All-Cause Mortality
Piperaquine Phosphate After Infected Blood Malaria Challenge
Affected / at Risk (%)
Total   0/6 (0.00%)    
Hide Serious Adverse Events
Piperaquine Phosphate After Infected Blood Malaria Challenge
Affected / at Risk (%) # Events
Total   0/6 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Piperaquine Phosphate After Infected Blood Malaria Challenge
Affected / at Risk (%) # Events
Total   6/6 (100.00%)    
Blood and lymphatic system disorders   
Lymphopenia *  1/6 (16.67%)  1
Gastrointestinal disorders   
Nausea *  1/6 (16.67%)  1
Vomiting *  1/6 (16.67%)  1
General disorders   
Chills *  1/6 (16.67%)  1
Fatigue *  1/6 (16.67%)  1
Hot flush *  1/6 (16.67%)  1
Malaise *  1/6 (16.67%)  1
Pyrexia *  1/6 (16.67%)  1
Injury, poisoning and procedural complications   
Contusion *  1/6 (16.67%)  1
Puncture site induration *  2/6 (33.33%)  3
Puncture site reaction *  2/6 (33.33%)  3
Investigations   
Lymphocyte count decreased   1/6 (16.67%)  1
Metabolism and nutrition disorders   
Decreased appetite *  1/6 (16.67%)  1
Musculoskeletal and connective tissue disorders   
Back pain *  1/6 (16.67%)  1
Myalgia *  3/6 (50.00%)  3
Nervous system disorders   
Headache *  4/6 (66.67%)  19
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
The adult mosquito mortality was high and blood feeding rates were low in these experiments, indicating an unhealthy mosquito colony. Transmission data from this group were therefore excluded from analysis.
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: NCT02431637    
Other Study ID Numbers: QP14C21
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