Clinical Investigation Study to Evaluate the Consistency and Reproducibility of Two Consecutive Mosquito Feeding Assays

Study Overview
=================
Brief Summary
-----------------
The proposed trial design has been developed to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval.

Detailed Description
-----------------
The proposed trial design has been developed to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval. The results will determine the type of pivotal trial design for a follow-on Phase 2b trial whose objective is to bridge the standard membrane feeding assay (SMFA) to the direct skin feeding assay (DSFA) and direct membrane feeding assay (DMFA) using a monoclonal antibody intervention, TB31F mAb, which interrupts transmission from human to mosquito. The results from this experimental medicine study will inform whether the preferred Before-After trial design in which each human volunteer serves as their own internal control can be utilized for a follow-on Phase 2b trial.

Official Title
-----------------
Clinical Investigation Study to Evaluate the Consistency and Reproducibility of Two Consecutive Mosquito Feeding Assays in Adults With Varying Plasmodium Falciparum Gametocyte Densities

Conditions
-----------------
Malaria

Intervention / Treatment
-----------------
* Other: to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed or thumb printed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female aged between 18 years and 55 years inclusive. Resident within the study area In good general health as evidenced by medical history and clinical examination before entering the study Ability to take oral Coartem and low-dose primaquine anti-malarials upon conclusion of day 2 (2nd direct skin feed) and be willing to adhere to the medication regimen For females, she must be of non-childbearing potential or use appropriate measures to prevent pregnancy for 30 days after receiving Coartem and primaquine. Non-childbearing potential means she is surgically sterilized or at least one year post-menopausal. Appropriate measures to prevent pregnancy include abstinence or adequate contraceptive precautions (i.e. intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant or Depo-Provera). For males, he must be willing to ensure that he does not get his partner(s) pregnant for at least 3 months after treatment with primaquine. Appropriate measures to prevent pregnancy include abstinence or adequate contraceptive precautions in either the participant or the partner. Positive for P. falciparum gametocytes as measured by PCR with cT value < 31. Exclusion Criteria: Presence of any signs or symptoms of malaria Presence of contraindications to administration of Coartem and primaquine as indicated in the respective drug package inserts History of severe allergic reactions to mosquito bites (other than pruritus and local swelling) Pregnant (i.e. a positive pregnancy test) Current or recent (within the preceding 2 weeks) use of antimalarial treatment Current participation in a malaria vaccine study Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval.|The results from this experimental medicine study will inform whether the preferred Before-After trial design in which each human volunteer serves as their own internal control can be utilized for a follow-on Phase 2b trial.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oocyst prevalence | Proportion of mosquitoes in a cup with at least one oocyst detected in the mid-gut among the mosquitoes (in the same cup) that underwent the feeding assays. | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oocyst density | Mean number of oocysts detected in infected mosquitoes that underwent feeding assays on the same subject | 2 days | 
| Sporozoite prevalence | Proportion of mosquitoes in a cup with at least one sporozoite detected in the salivary glands among the mosquitoes (in the same cup) that underwent feeding assays | 2 days | 
| Sporozoite density | Mean number of sporozoites detected in infected mosquitoes that underwent feeding assays | 2 days |