Clinical trial NCT04666350: Clinical Investigation Study to Evaluate the Consistency and Reproducibility of Two Consecutive Mosquito Feeding Assays
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Malaria
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Walter Reed Army Institute of Research (WRAIR)
name: Kenya Medical Research Institute
First posted: 2020-12-14
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target sample size for subjects with gametocytemia is approximately 45 individuals. Approximately 180 participants will be screened for gametocyte carriage by PCR to achieve the target sample size. Screening of subjects will continue until the desired sample size of gametocytemic individuals who undergo all study procedures is attained. Adults aged 18 - 55 years will be recruited from the villages in the Kombewa Health and Demographics Surveillance System (HDSS) consisting of half of Kisumu

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 monoclonal antibody (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.

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 polymerase chain reaction (PCR) with cycle threshold (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.

Primary outcomes:
measure: Oocyst Prevalence
timeFrame: Feeding assays were performed on Day 1 and Day 2; Oocyst prevalence in surviving mosquitoes was assessed 9 days after feeding (Days 9 and 10).
Secondary outcomes:
measure: Oocyst Density
timeFrame: Feeding assays were performed on Day 1 and Day 2; Oocyst density in surviving mosquitos was assessed 9 days after feeding (Days 9 and 10).
measure: Sporozoite Prevalence
timeFrame: Feeding assays were performed on Day 1 and Day 2; Sporozoite prevalence in surviving mosquitoes was assessed 14 days after feeding (Days 14 and 15).
measure: Sporozoite Density
timeFrame: Day 1 and Day 2
Other outcomes:
Locations:
city: Kombewa
country: Kenya
facility: KEMRI
Study officials:
affiliation: Drug Resistance Laboratory, KEMRI
name: Ben Andagalu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Drug Resistance Laboratory, KEMRI
name: Hoseah Akala, MD
role: PRINCIPAL_INVESTIGATOR
References: