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Plasmodium Falciparum InfectionPhase 1NCT03014258

A Systems Biology Approach to Malaria Immunity

A Phase 1 study testing NF54 P. falciparum malaria challenge in people with Plasmodium Falciparum Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Plasmodium Falciparum Infection
What is being tested?
NF54 P. falciparum malaria challenge
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
7 Jun 2017to 19 Jul 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Male or non-pregnant/non-lactating female between the ages of 18 and 50 years, inclusive.
  • Able and willing to participate for the duration of the study.
  • Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  • Able and willing to complete the informed consent process.
  • Willing to donate blood for sample storage to be used for future research (Note: refusal to allow future use is exclusionary).
  • Willing to refrain from blood donation to blood banks for 3 years following P. falciparum CHMI.
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  • Agrees not to travel to a malaria endemic region during the entire course of study participation.
  • Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) = / < 35.
  • Laboratory Criteria within 56 days prior to enrollment:
  • Hemoglobin = / >11.2 g/dL for women; = / > 12.6 g/dL for men.
  • Platelet count within institutional normal range.
  • Alanine aminotransferase (ALT) = / < upper limit of normal.
  • Serum creatinine = / < upper limit of normal.
  • Negative for HIV and Hepatitis B/C infection.
  • Laboratory Criterion documented any time prior to enrollment:
  • Negative sickle cell screening test.
  • Female-Specific Criteria:
  • Negative beta-HCG pregnancy test (serum) on day of screening or urine pregnancy test at subsequent time points for women of childbearing potential.
  • Women of childbearing potential (exclusive of women in a same sex relationship) must agree to use effective means of birth control.* *(e.g. oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner). Women with a history of amenorrhea (> 1 year duration) or surgical or chemical sterilization (e.g. tubal ligation, hysterectomy, other) must provide written documentation of infertility from a health care provider.

Who cannot join

  • Women who are breast-feeding or planning to become pregnant during the time interval needed to complete the study.
  • Receipt of a malaria vaccine in a prior clinical trial.
  • Any history of malaria infection.
  • Evidence of increased cardiovascular disease risk; defined as > 10% five year risk by the non-laboratory method.
  • Current use of systemic immunosuppressant pharmacotherapy.
  • History of a splenectomy, sickle cell disease or sickle cell trait.
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  • Known history of anaphylactic response to mosquito-bites; or known allergy to artemether lumefantrine or atovaquone or proguanil or other component of the product.
  • Participation in any study involving investigational vaccine or drug within 4 weeks prior to enrollment, or expects to receive vaccine or drug during the 2-month post-challenge period.
  • Use or planned use of any drug with anti-malarial activity that would coincide with challenge.
  • Anticipated use of medications known to cause drug reactions with atovaquone-proguanil (Malarone(R)) such as cimetidine, metoclopramide, antacids, and kaolin.
  • Plans to undergo surgery (elective or otherwise) between enrollment and 4 weeks (28 days) after any of the challenges.
  • Received a licensed vaccine within 1 month prior to enrollment in this study or expects to receive one during the 28 day post challenge period.
  • History of psychiatric disorders or behavioral tendencies (including active alcohol or drug abuse) that in the opinion of the investigator would make compliance with the protocol difficult.* *Medical and psychiatric illness defined as personality disorders, anxiety disorders, or schizophrenia or social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent or to comply with the protocol schedule.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

    Baltimore, Maryland, 21201-1509

Other trials in United States

About this study

Official title: A Systems Biology Approach to Malaria Immunity: Repetitive Controlled Human Malaria Infection (CHMI) Study in Malaria-Naïve Adults Using NF54 Strain Plasmodium Falciparum (Pf)

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.

Read the detailed description

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.

Being tested
NF54 P. falciparum malaria challenge
Keywords
Biology, falciparum, Immunity, Infections, Malaria, Pf, Plasmodium, Systems
Medical subject headings
Infections, Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NF54 P. falciparum malaria challengeBiological

    Aseptically-raised A. stephensi female mosquitoes infected with aseptically-raised P. falciparum parasites of the NF54 strain.

Study groups in NCT03014258
Study groupRoleWhat they receive
Control Cohort 1Active comparatorImmunologic malaria-naïve subjects will undergo CHMI #2 with 5 NF54 P. falciparum-infected mosquitoes at months 8-9. n=6.
Receives: Biological: NF54 P. falciparum malaria challenge
Control Cohort 2Active comparatorImmunologic malaria-naïve subjects will undergo a CHMI #3 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #2. n=6.
Receives: Biological: NF54 P. falciparum malaria challenge
Control Cohort 3Active comparatorImmunologic malaria-naïve subjects will undergo a CHMI #4 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #3. n=6.
Receives: Biological: NF54 P. falciparum malaria challenge
Control Cohort 4Active comparatorImmunologic malaria-naïve subjects will undergo a CHMI #5 with 5 NF54 P. falciparum-infected mosquitoes at 6-12 months post CHMI #4. n=6.
Receives: Biological: NF54 P. falciparum malaria challenge
Repeat CHMIExperimentalSubjects 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.
Receives: Biological: NF54 P. falciparum malaria challenge

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of subjects testing positive for parasites

    As measured using real-time quantitative polymerase chain reaction (PCR)

    Measured: Study Day 6 through Study Day 29

  2. 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

    Measured: Study Day 9 through Study Day 29

  3. Quantification of parasite infection

    As measured using real-time quantitative polymerase chain reaction (PCR) during the surveillance period after infected CHMI.

    Measured: Study Day 6 through Study Day 29

Secondary outcomes (6)
  1. 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.

    Measured: Up to Study Day 21

  2. 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.

    Measured: Up to Study Day 21

  3. 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.

    Measured: Up to Study Day 21

  4. 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.

    Measured: Up to Study Day 21

  5. Percentage of subjects displaying signs and symptoms attributable to malaria

    Such as malaise, chills/rigors, nausea, vomiting, dizziness, arthralgia, abdominal pain, myalgia, and headache

    Measured: Study Day 6 through Study Day 29

  6. Percentage of subjects with fever attributable to malaria

    Fever as defined as >38 degrees Celsius

    Measured: Study Day 6 through Study Day 29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2017 (estimated)
  2. Study start7 Jun 2017
  3. Primary completion19 Jul 2019
  4. Study completion19 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03014258
Sponsor's protocol ID
15-0058
Status last verified
27 May 2021
First submitted
15 Dec 2016
Last updated
8 Jun 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ferrer P, Berry AA, Bucsan AN, Prajapati SK, Krishnan K, Barbeau MC, Rickert DM, Guerrero SM, Usui M, Abebe Y, Patil A, Chakravarty S, Billingsley PF, Pa'ahana-Brown F, Strauss K, Shrestha B, Nomicos E, Deye GA, Sim BKL, Hoffman SL, Williamson KC, Lyke KE. Repeat controlled human Plasmodium falciparum infections delay bloodstream patency and reduce symptoms. Nat Commun. 2024 Jun 18;15(1):5194. doi: 10.1038/s41467-024-49041-2.

    PubMed 38890271

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NF54 P. falciparum malaria challenge in people with Plasmodium Falciparum Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of subjects testing positive for parasites (time frame: Study Day 6 through Study Day 29). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03014258, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.

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A Systems Biology Approach to Malaria Immunity | AzTrials