Malaria CVD 36000; Gates INV090205

Phase I, Double-blind, Randomized Study of Physiological Parameters Biosensor Detection Device(s) Diagnosis of P. Falciparum NF54 Strain Malaria Following Controlled Human Malaria Infection and Post-hoc Analysis of Wearable Biosensor Device Detection

In order to control infections, the investigators must first detect them. Biosensor devices may allow early detection and intervention for infectious diseases, helping the investigators to recognize infections early, and allow for early treatment. This will lower transmission of infections and lower costs for treating someone who becomes ill. This is a study testing whether a wearable device such as a wristband and/or earphones can measure early biologic signals to detect identify infection in prior to seeing symptoms related of a disease. As a first test of this technology, the investigators will expose participants to injectable malaria or placebo. This is called a "Controlled Human Malaria Infection" (CHMI). Everyone who takes part in the CHMI may get malaria infection. The investigators will detect malaria using standard blood tests. The investigators will also look for early symptoms of malaria infection like changes in temperature, heart rate, breathing, sleep patterns, and changes in skin and muscle activity or voice. These signals may allow the investigators to detect early malaria infection. This is a study testing whether a wearable device such as a wristband and/or earphones can measure early biologic signals to detect malaria infection before symptoms occur, as confirmed by standard blood testing.

Study Overview

• Status: Not yet recruiting
• Conditions: Malaria (Plasmodium Falciparum)
• Intervention / Treatment: Other: Placebo; Biological: PfSPZ Challenge (NF54); Device: Wearable Biosensor Devices

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kirsten Lyke, MD; Phone Number: 410-706-6156; Email: klyke@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore, Center for Vaccine Development and Global Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or non-pregnant, non-breastfeeding female between 18 and 50 years of age (inclusive) at the time of consent.
2. Participants must be able to provide written informed consent.
3. Participants must be healthy as established by medical history and clinical examination at study entry.
4. Participants must pass a comprehension (defined as 80%) test and be able to comply with all study requirements.
5. Both males and females are eligible to participate as per the following:

Participants physically capable of pregnancy must agree to use effective contraception to avoid pregnancy from 28 days before enrollment through 10 months after last administration of investigational product are eligible to participate. An effective contraceptive method is defined as one that results in a failure rate of less than 1% per year when it is used consistently and correctly. Adequate contraceptive precautions include intrauterine contraceptive device, oral contraceptives, diaphragm, or condom in combination with contraceptive jelly, cream, or foam; Norplant® or Depo-Provera®, through the completion of study visits to minimize any potential risk.

i. Effective contraception does not apply to participants of child-bearing potential with same sex partners, when this is their preferred and usual lifestyle.

ii. Adequate contraception does not apply to women with documented surgical sterility (tubal ligation, bilateral oophorectomy, salpingectomy, or hysterectomy), congenital sterility, who have a diagnosis of infertility and are not undergoing treatment, or women who have not had a menstrual period in at least 1 year

Exclusion Criteria:

1. Women who are pregnant or breastfeeding
2. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required)
3. History of malaria infection, or history > 6 months spent in a malaria endemic region within 5 years prior to enrollment.

4. Participant seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV).

   Note: Prior participants of HIV vaccine studies may result in a false positive HIV antibody test, as such, in this scenario, participant will be eligible if they have a negative HIV RNA PCR at screening.

5. Safety laboratory test results within range at screening (as per FDA Toxicity Grading Scale, see Appendix A):

   • White Blood Cell (WBC) 3,500-12,000/mm3
   • WBC differential either within institutional normal range or accompanied by the PI or designee approval
   • Platelets = 125,000 - 500,000/mm3
   • Hemoglobin within institutional normal range or accompanied by the PI or designee approval
   • Creatinine ≤ 1.1 x upper limit of normal (ULN)
   • ALT ≤1.25 x ULN
   • Grade 1 subclinical abnormalities in other chemistries will not lead to exclusion if the investigator considers them not clinically significant
6. A 5-year cardiovascular risk of >10% using the Gaziano nomogram (Appendix B)
7. Significant screening physical examination abnormalities at the discretion of the investigator, including a BMI > 35 kg/m2
8. Electrocardiogram (ECG) with clinically significant abnormalities (examples may include: pathologic Q waves, significant ST-T wave changes, left ventricular hypertrophy, any non-sinus rhythm excluding isolated premature atrial contractions, right or left bundle branch block, advanced A-V heart block). ECG abnormalities determined by an investigator to be clinically insignificant as related to trial participation do not preclude trial enrollment. Consultation may be sought by a cardiologist at investigator discretion.
9. Known intolerance to atovaquone or proguanil, and either artemether/lumefantrine or chloroquine phosphate
10. Routine use of antibiotics, or use of antibiotics with known antimalarial effect (azithromycin, trimethoprim/sulfamethoxazole or tetracyclines) within 4 weeks prior to CHMI.
11. Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone®) such as cimetidine, metoclopramide, antacids, and kaolin.
12. Administration of immunoglobulins and/or any blood products during the period starting 90 days preceding the CHMI or planned administration during the study period
13. Planned administration or administration of a live vaccine/product not planned in the study protocol during the period starting 30 days prior to the CHMI until the study completion (routine vaccinations will be allowed if it is not administered within 14 days preceding or 21 days following CHMI)
14. Use of any investigational or non-registered product (drug or vaccine during the period starting 30 days preceding the CHMI and/or planned use during the study period
15. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90days prior to the CHMI (for corticosteroids, this will mean prednisone >5mg/day or equivalent; inhaled, intranasal and topical steroids are allowed)
16. Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device)
17. Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or blood draws
18. History of a splenectomy, sickle cell disease or sickle cell trait
19. History of skeeter syndrome or anaphylactic response to mosquito-bites
20. Autoimmune disease or history of autoimmune disease
21. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study product or related to a study procedure
22. Major congenital defects or serious chronic illness
23. Presence of any implanted device which could bias biosensor data (e.g., pacemaker, etc.)
24. Acute disease and/or fever (≥37.5°C/99.5°F oral body temperature) at the time of enrollment: note that a participant with a minor illness such as mild diarrhea, mild upper respiratory infection, etc., without fever, may be enrolled at the discretion of the investigator
25. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, neurological disorders, seizures or renal functional abnormality, as determined by history, physical examination or laboratory screening tests
26. History of bipolar disorder, schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the participant from participating in the study
27. Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the Investigator, will make it unlikely that the participant will comply with the protocol.
28. Any other condition which, in the opinion of the investigator, prevents the participant from participating in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PfSPZ Challenge; 0.5 mL single-dose of PfSPZ Challenge (strain NF54)	Biological: PfSPZ Challenge (NF54); PfSPZ Challenge (NF54) administered as a single dose by direct venous inoculation (DVI); Device: Wearable Biosensor Devices; Investigational, wearable biosensing devices. The objective would be to collect biosensor data for correlation to known malaria infection by reference diagnostic testing and with physiological (clinical) data.
Placebo Comparator: Placebo; Normale saline placebo	Other: Placebo; Normal saline placebo; Device: Wearable Biosensor Devices; Investigational, wearable biosensing devices. The objective would be to collect biosensor data for correlation to known malaria infection by reference diagnostic testing and with physiological (clinical) data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of detectable malaria parasitemia following controlled human malaria infection exposure by the Direct Venous Inoculation (DVI) of cryopreserved P. falciparum NF54-strain sporozoites	Presence or absence of RT-qPCR through Day 28 (unit - Ct value)	From challenge to the end of participation at day 56
Presence of detectable malaria parasitemia following controlled human malaria infection exposure by the Direct Venous Inoculation (DVI) of cryopreserved P. falciparum NF54-strain sporozoites	Presence of absence of Thick Blood Smear - unit - parasite/mm3 or mL	From challenge to the end of participation at day 56
Time of detectable malaria parasitemia following controlled human malaria infection exposure by the Direct Venous Inoculation (DVI) of cryopreserved P. falciparum NF54-strain sporozoites	Time to Pf infection (unit - days)	From challenge to the end of participation at day 56
Presence or absence of temperature associated with pre-infection, asymptomatic parasitemia and symptomatic parasitemia		From challenge to the end of participation at day 56
Presence or absence of heart Rate changes associated with pre-infection, asymptomatic parasitemia and symptomatic parasitemia		From challenge to the end of participation at day 56
Presence or absence of Respiratory Rate associated with pre-infection, asymptomatic parasitemia and symptomatic parasitemia		From challenge to the end of participation at day 56
Presence or absence of Solicited Systemic Symptoms associated with pre-infection, asymptomatic parasitemia and symptomatic parasitemia	(yes/no to headache, fatigue/malaise, myalgia, arthralgia, nausea, abdominal pain, vomiting)	From challenge to the end of participation at day 56

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Bill and Melinda Gates Foundation; Sanaria Inc.; University of Texas at Austin

Study record dates

Study Major Dates

• Study Start (Estimated): June 13, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Malaria, Falciparum
• Other Study ID Numbers: HP-00118316

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes