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

NCT ID: NCT04666350

Last Updated: 2024-04-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 42 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-03-09
• Study Completion Date: 2021-12-20

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.

Conditions

Malaria

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Study Volunteers

Participants provided a blood sample on Day 1 for DMFA testing and then participated in the mosquito feeding assay. On Day 2 participants underwent a second DMFA and DSFA assay (within 24 hours of the first assays).

Upon completion of Day 2 DSFA participants will receive one dose of primaquine and the first dose of a 3-day regiment of artemether/lumefantrine.

Direct Skin Feeding Assay (DSFA)

Intervention Type: OTHER

In the direct feeding assay a cup with 60 unfed, sterile insectary-reared Anopheles gambiae mosquitoes will be allowed to feed on a participant's calf or arm for 15 minutes.

Primaquine

Intervention Type: DRUG

Participants will receive one dose of primaquine 26.3 mg tablet on Day 2 after completion of the direct feeding assay.

Artemether/Lumefantrine

Intervention Type: DRUG

Participants will receive artemether (80 mg) and lumefantrine (480 mg) combination tablets twice a day for 3 days, starting after completion of the direct feeding assay on Day 2.

Interventions

Direct Skin Feeding Assay (DSFA)

In the direct feeding assay a cup with 60 unfed, sterile insectary-reared Anopheles gambiae mosquitoes will be allowed to feed on a participant's calf or arm for 15 minutes.

Intervention Type: OTHER

Primaquine

Participants will receive one dose of primaquine 26.3 mg tablet on Day 2 after completion of the direct feeding assay.

Intervention Type: DRUG

Artemether/Lumefantrine

Participants will receive artemether (80 mg) and lumefantrine (480 mg) combination tablets twice a day for 3 days, starting after completion of the direct feeding assay on Day 2.

Intervention Type: DRUG

Other Intervention Names

Coartem®

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role: collaborator

PATH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ben Andagalu, MD

Role: PRINCIPAL_INVESTIGATOR

Drug Resistance Laboratory, KEMRI

Hoseah Akala, MD

Role: PRINCIPAL_INVESTIGATOR

Drug Resistance Laboratory, KEMRI

Locations

KEMRI

Kombewa, , Kenya

Countries

Kenya

References

Akala HM, Aponte JJ, Achola MA, Juma DW, Opot BH, Maisiba RN, Okoth RO, Juma JA, Mwakio EW, Mwalo MA, Oullo DO, Abuom D, Garges EC, Eyase FL, Tina LO, Copeland NK, Roth A, Mutunga J, Onyango I, Johnson J, Ogutu BR, Sifuna P, Hutter J, Mercer L, Raine M, Moore V, Ivinson K, Wu Y, Andagalu B, Ockenhouse CF. Consistency and reproducibility of independent feedings using blood from two consecutive days at varying Plasmodium falciparum gametocyte densities based on both direct membrane feeding assay and direct skin feeding assay. Malar J. 2025 May 16;24(1):154. doi: 10.1186/s12936-025-05360-3.

Reference Type: DERIVED

PMID: 40380146 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CVIA 085 -- Phase 0

Identifier Type: -

Identifier Source: org_study_id