Assessing the safety and infectivity of a malaria challenge agent in healthy adults

Phase 1 Study of Induced Blood-Stage Malaria in Healthy Malaria-Naive Adults to Assess the Safety and Infectivity of Plasmodium Vivax Challenge Agent and Evaluate Transmission in Mosquito Feeding Assays

This study is testing how the malaria parasite affects healthy adults and how their immune systems respond, to help develop better vaccines.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years to 54 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: prednisone
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT06607003 on ClinicalTrials.gov

What this trial studies

This study aims to understand how malaria develops in humans and how the immune system responds to the Plasmodium vivax parasite. Healthy participants aged 18 to 54 will be infected with the malaria parasite through an intravenous injection of donated blood. The study will monitor their health daily and conduct blood tests to evaluate the safety and infectivity of the challenge agent. Additionally, the study will assess how malaria can be transmitted to mosquitoes, which is crucial for developing future transmission-blocking vaccines.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 18 to 54 who are malaria-naive and can comply with study requirements.

Not a fit: Patients who are planning to travel to malaria-endemic areas during the study period will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and prevention strategies for malaria, potentially aiding in vaccine development.

How similar studies have performed: While this approach is novel in its specific application, similar studies have shown promise in understanding malaria transmission and immune responses.

Eligibility criteria

* INCLUSION CRITERIA:

All of the following criteria must be fulfilled for a participant to undergo IBSM:

1. Age \>=18 and \<=54 years.
2. RBCs positive for Duffy antigen/chemokine receptor.
3. Malaria comprehension exam passed prior to study activities.
4. Suitable accommodation and reliable access to the NIHCC for the duration of the study in the opinion of the investigator.
5. Persons of childbearing potential must be willing to use reliable contraception from 28 days prior to challenge agent administration to the end of study.
6. Signing of the informed consent form.
7. Agreement to not live alone from challenge agent administration until the completion of antimalarial treatment.
8. Agreement to long-term storage of study samples for future research.

EXCLUSION CRITERIA:

A participant will be excluded from participating in this trial if any 1 of the following criteria is fulfilled:

1. Planned travel to a P. vivax-endemic area during the study period (see https://www.cdc.gov/malaria/travelers/country\_table/a.html).
2. History of travel to or residence in a P. vivax malaria-endemic region for more than 2 weeks during the past 2 years.
3. Prior confirmed P. vivax malaria diagnosis or clinical history consistent with likely P. vivax infection. At the investigator's discretion, participants may be enrolled if the exposure was remote, e.g., \> 5 years ago.
4. Poor peripheral venous access, at the discretion of the investigator.
5. For persons of childbearing potential:

   1. Currently pregnant or breastfeeding, or planning on becoming pregnant or breastfeeding until the end of study.
   2. Rh blood group negative.
6. Being a current or former study team member or clinical trial staff with direct involvement of the trial, or being an employee supervised by a study team member.
7. Unwillingness to defer blood donations for at least 3 years.
8. Use of any of the following within the specified periods:

   1. Investigational P. vivax vaccine within the last 2 years.
   2. Malaria chemoprophylaxis within 3 months of Day 0.
   3. Chronic systemic immunosuppressive medications (\>14 days) within 6 months (e.g., cytotoxic medications, adrenocorticotrophic hormone, or oral/parental corticosteroids equivalent to \>0.5 mg/kg/day of prednisone). Corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are allowed.
   4. Prior receipt of packed red cells or other blood products or immunoglobulins within the previous 6 months.
   5. Systemic antibiotics or medications with potential antimalarial effects less than 28 days before Day 0 (e.g., clindamycin, chloroquine, benzodiazepines, tetracycline, azithromycin, or doxycycline).
   6. Investigational product or vaccine less than 28 days before Day 0.
   7. Receipt of any vaccination less than 28 days before Day 0.
   8. Current or planned use of medications known to significantly prolong the QT interval or otherwise interfere with study agents.
   9. Smoking more than 5 cigarettes or equivalent per day and unable to stop smoking for the duration of admission. Participants may smoke up to 5 cigarettes or equivalent per day for the rest of the study (by attestation).
   10. History of alcohol use disorder (exceptions may be made at the investigator's discretion if they have completed treatment or are otherwise currently abstinent) or refusal to agree to refrain from drinking from the day of the challenge agent inoculation until completion of their antimalarial course.
9. Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history including:

   1. Immunodeficiency including asplenia or functional asplenia or significant autoimmune disease.
   2. Retinal disease, visual field changes, psoriasis, porphyria, or known allergy to chloroquine or artemether/lumefantrine.
   3. Cardiac disease including \>10 percent cardiovascular risk as determined by the non-laboratory method or an abnormal EKG demonstrating a corrected QT interval by Fridericia's formula of \>450 msec or other concerning arrhythmia.
   4. Any other medical condition that may have significant implications for current health status and participation in the study, in the opinion of the investigator.
10. History of a severe reaction to arthropod bites, or history of anaphylaxis or severe unexpected allergy to any substance.
11. Screening blood test or urinalysis laboratory parameters outside of local lab normal range (including infectious serologies). Participants may be included at the investigator's discretion for "not clinically significant" values outside of normal range.
12. Any other finding that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a participant's ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study.

Participants who are determined ineligible to participate for any of the reasons above may be rescreened for eligibility at a later time when the disqualifying condition may be resolved.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Joel A Goldberg, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: Joel A Goldberg, M.D.

Conditions Malaria; IBSM; Challenge; inoculation; Parasitemia; Mosquito Feeding Assay; Malaria Transmission