A Phase 1 interventional study of NF54 P. falciparum malaria challenge in Plasmodium Falciparum Infection, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 1 site in United States. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-06-08.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Other
This is a phase I study that will assess the acquisition of immunity to Pf malaria over the course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10 healthy adult participants. 10 subjects will initially be challenged with 5 uninfected mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive, P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled and challenged as infectivity controls. If dropouts occur within the original 10 person cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily follow-up) to diagnose Pf malaria infection and treat with Coartem(R) (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection is complete and two negative smears separated by a time interval >12 hours have been documented. A third negative smear >12 hours after the previous two daily smears will be documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor the development of immunity. The study is expected to last for 48 months and will include approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years, inclusive, from the greater Baltimore community. The primary objective of this study is to determine whether protective immunity against parasite infection develops following repeat CHMI.
This is a phase I study that will assess the acquisition of immunity to Pf malaria over the course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10 healthy adult participants. 10 subjects will initially be challenged with 5 uninfected mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive, P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled and challenged as infectivity controls. If dropouts occur within the original 10 person cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily follow-up) to diagnose Pf malaria infection and treat with Coartem(R) (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection is complete and two negative smears separated by a time interval >12 hours have been documented. A third negative smear >12 hours after the previous two daily smears will be documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor the development of immunity. The study is expected to last for 48 months and will include approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years, inclusive, from the greater Baltimore community. The primary objective of this study is to determine whether protective immunity against parasite infection develops following repeat CHMI. The secondary objectives are to: 1) determine whether clinical signs and symptoms of malaria decrease in intensity and duration following repeat CHMI, 2) track the production of antibodies that react with P. falciparum sporozoites and blood stage parasites.
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This study's enrollment of 27 is below the median of 120 across 4,200 interventional studies indexed under Infections.
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Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) = / \< 35.
Laboratory Criteria within 56 days prior to enrollment:
Negative for HIV and Hepatitis B/C infection.
Laboratory Criterion documented any time prior to enrollment:
Negative sickle cell screening test.
Female-Specific Criteria:
Exclusion Criteria:
Immunologic malaria-naïve subjects will undergo CHMI #2 with 5 NF54 P. falciparum-infected mosquitoes at months 8-9. n=6.
Biological: NF54 P. falciparum malaria challenge
Immunologic malaria-naïve subjects will undergo a CHMI #3 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #2. n=6.
Biological: NF54 P. falciparum malaria challenge
Immunologic malaria-naïve subjects will undergo a CHMI #4 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #3. n=6.
Biological: NF54 P. falciparum malaria challenge
Immunologic malaria-naïve subjects will undergo a CHMI #5 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #4. n=6.
Biological: NF54 P. falciparum malaria challenge
Subjects will initially be challenged with 5 uninfected mosquitoes (mock), followed by 5 challenges (CHMI # 1-5) with 5 NF54 P. falciparum-infected mosquitoes 2, 8, 14-20, and 20-32, and 32-36 months later. n=10.
Biological: NF54 P. falciparum malaria challenge
Aseptically-raised A. stephensi female mosquitoes infected with aseptically-raised P. falciparum parasites of the NF54 strain.
Percentage of subjects testing positive for parasites
As measured using real-time quantitative polymerase chain reaction (PCR)
Time frame: Study Day 6 through Study Day 29
Percentage of subjects with positive malaria smear
For infectivity controls enrolled into infective CHMI #5, malaria detection will rely upon ultra-sensitive quantitative polymerase chain reaction (us-qPCR) to ensure safety while conducting this portion of the study as an outpatient
Time frame: Study Day 9 through Study Day 29
Quantification of parasite infection
As measured using real-time quantitative polymerase chain reaction (PCR) during the surveillance period after infected CHMI.
Time frame: Study Day 6 through Study Day 29
Antibody reactivity against Circumsporozoite protein (CSP)
Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.
Time frame: Up to Study Day 21
Antibody reactivity against Glutamate-rich protein (GLURP)
Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.
Time frame: Up to Study Day 21
Antibody reactivity against Plasmodium Falciparum liver- and erythrocytic-stage antigen
Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.
Time frame: Up to Study Day 21
Antibody reactivity against Plasmodium Falciparum pre-erythrocytic antigen
Measured using plasma obtained during the surveillance period. Antibody reactivity is defined as the optical density at 410 nM of a 1/300 dilution of the volunteers plasma sample minus the optical density at 410 nM of a 1/300 dilution of the volunteer's baseline sample.
Time frame: Up to Study Day 21
Percentage of subjects displaying signs and symptoms attributable to malaria
Such as malaise, chills/rigors, nausea, vomiting, dizziness, arthralgia, abdominal pain, myalgia, and headache
Time frame: Study Day 6 through Study Day 29
Percentage of subjects with fever attributable to malaria
Fever as defined as \>38 degrees Celsius
Time frame: Study Day 6 through Study Day 29
This study is completed, as verified in May 2021. You cannot join it, but the record below documents what was studied.
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National Institute of Allergy and Infectious Diseases (NIAID)