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MalariaPhase 1NCT02015091

Study of Controlled Human Malaria Infections to Evaluate Protection After Intravenous or Intramuscular Administration of PfSPZ Vaccine in Malaria-Naive Adults

A Phase 1 study testing PfSPZ Vaccine in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites 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

Background: People bitten by mosquitoes carrying weakened malaria parasites could fight off the disease if later exposed to normal malaria parasites. Scientists have discovered how to make the weakened parasites, which can be injected by the PfSPZ vaccine. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Malaria
What is being tested?
PfSPZ Vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
141 participants
Where
2 sitesUnited States
Study dates
12 Dec 2013to 8 Sep 2016
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 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • A volunteer must meet all of the following criteria to be included:
  • 18 to 45 years old adults.
  • 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.
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  • Willing to refrain from blood donation to blood banks for 3 years following P. falciparum CHMI.
  • 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) less than or equal to 35 for vaccine groups or BMI less than or equal to 40 for control groups.
  • If enrolling into a Group with an IV vaccination schedule, then the physical exam must include assessment that there is adequate bilateral antecubital fossa venous access.
  • Laboratory Criteria within 56 days prior to enrollment:
  • Hemoglobin greater than or equal to 11.2 g/dL for women; greater than or equal to 12.6 g/dL for men.
  • Differential and platelet count either within institutional normal range or accompanied by site physician approval.
  • Alanine aminotransferase (ALT) less than or equal to 1.25 x upper limit of normal (ULN) for vaccine groups or less than or equal to 1.75 x ULN for CHMI control groups.
  • Serum creatinine less than or equal to upper limit of normal.
  • Negative for HIV infection.
  • Laboratory Criterion documented any time prior to enrollment:
  • Negative sickle cell screening test.
  • Female-Specific Criteria:
  • Negative Beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed to be of childbearing potential.
  • A woman of childbearing potential must agree to use an effective means of birth control throughout the duration of study participation.

Who cannot join

  • A volunteer will be excluded if one or more of the following conditions apply:
  • Woman who is 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.
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  • History of a splenectomy, sickle cell disease or sickle cell trait.
  • Plan for major surgery between enrollment and challenge.
  • Known allergy to any component of the vaccine formulation; history of anaphylactic response to mosquito-bites; or known allergy to chloroquine phosphate, atovaquone or proguanil.
  • Participation in any study involving another investigational vaccine or drug within 12 weeks prior to enrollment, or plan to participate in another investigational vaccine/drug research during the study.
  • Personal beliefs that prohibit the receiving of vaccine product containing human serum albumin within the diluent.
  • Use or planned use of any drug with anti-malarial activity that would coincide with study vaccination or challenge.
  • History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine.
  • Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and kaolin.
  • Psychiatric condition that precludes compliance with the protocol; past or present psychoses; disorder requiring lithium; or within five years prior to enrollment, history of a suicide plan or attempt.
  • Any medical, psychiatric, 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

2 sites in 1 country.

United States2 sites
  • University of Maryland Center for Vaccine Dev, Baltimore

    Baltimore, Maryland, 21201-1595

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: VRC 314: A Phase 1, Open-Label, Clinical Trial With Experimental Controlled Human Malaria Infections (CHMI) to Evaluate Safety and Durability of Protection Following Intravenous and Intramuscular Administration of PFSPZ Vaccine in Malaria-Naive Adults

Background:

  • People bitten by mosquitoes carrying weakened malaria parasites could fight off the disease if later exposed to normal malaria parasites. Scientists have discovered how to make the weakened parasites, which can be injected by the PfSPZ vaccine. Researchers want to see if people who receive the vaccine get malaria after being bitten in a controlled setting (a controlled human malaria infection, CHMI).
Read more

Objective:

  • To see if the PfSPZ malaria vaccine is safe and prevents malaria in a controlled setting.

Eligibility:

  • Healthy adults 18 45 years old.

Design:

  • Participants will be screened with medical history, physical exam, blood and lab tests, and EKG.
  • Participants will be split into 8 groups, to be in the study for 3 12 months.
  • Participants will receive 3 5 vaccinations, injected by a needle in an arm vein or muscle.
  • Participants will keep a health diary and be contacted by phone.
  • For CHMI, a cup with mosquitoes carrying malaria is applied to participants arm for 5 minutes. Five mosquitoes at a time are used, until 5 have bitten. Some groups will be exposed to malaria more than once.
  • After CHMI, participants will visit the clinic very frequently (including daily visits for 12 days) for 28 days.
  • Blood will be drawn at most visits, from 1 to 20 tubes. Physical exam and medical history may also be repeated
  • Participants who develop malaria will be treated immediately at the clinic. Standard treatment takes 72 hours. Malaria symptoms may last up to 3 days.
Read the detailed description

VRC 314 is designed as an open-label evaluation of the safety, tolerability, immunogenicity and protective efficacy of PfSPZ Vaccine. This vaccine administered at 1.35 times 10(5) PfSPZ per injection by the IV route on a schedule of 5 vaccinations was previously shown to confer protection in all vaccinated subjects against CHMI performed shortly after last vaccination; however there was limited durability of protection in a small number of protected subjects who were rechallenged several months later. This study is designed to substantiate the initial results with the IV vaccination route for protection against CHMI. Based on the potential importance of dose and schedule in optimizing sustained immunity with this vaccine, an increase in PfSPZ IV dosage on schedules of 3 to 5 vaccinations will be evaluated for protection against CHMI conducted early (about 3 weeks) and late (about 24 weeks) after completion of vaccinations. To assess if a higher dose given by another route confers protection, one group will receive PfSPZ IM, with half of the amount administered in each arm on a schedule with 4 vaccination.

The primary objectives of the study are related to the safety and tolerability of vaccinations by the IV and IM routes of administration and protection against Plasmodium falciparum (Pf) challenge performed via a well-established CHMI procedure early (2-4 weeks) after completing schedules of 3 to 5 vaccinations. The secondary objective is related to the durability of protection at 20-26 weeks after the last vaccination and exploratory objectives are related to the immunogenicity of the PfSPZ Vaccine and identifying potential immune correlates of protection.

Conditions
Malaria
Being tested
PfSPZ Vaccine
Keywords
Healthy Subjects, Vaccine-Mediated Protection, Immunogenicity, Sporozoites, Parasitemia
Medical subject headings
Malaria, Parasitemia

What participants receive

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

  • PfSPZ VaccineBiological

    The PfSPZ Vaccine is composed of radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) and is designed to prevent malaria in adults, children, and infants. It is formulated in phosphate buffered saline (PBS) with 1% human serum albumin (HSA). Sanaria Incorporated (Sanaria), Rockville, Maryland, developed and produced the PfSPZ Vaccine.

Study groups in NCT02015091
Study groupRoleWhat they receive
1, 4, 5, 6, 7ExperimentalVaccination schedules with 3 to 4 IV vaccinations per subject. Evaluation of protection against controlled human malaria infection (CHMI) is included.
Receives: Biological: PfSPZ Vaccine
2ExperimentalVaccination schedules 4 IM vaccinations per subject. Evaluation of protection against controlled human malaria infection (CHMI) is included.
Receives: Biological: PfSPZ Vaccine
3ExperimentalVaccination schedules 5 IV vaccinations per subject. Evaluation of protection against controlled human malaria infection (CHMI) is included.
Receives: Biological: PfSPZ Vaccine
8No interventionParticipation in controlled human malari infection (CHMI) without prior vaccinations to serve as controls.

What is being measured

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

  1. To evaluate the safety and tolerability of the metabolicallyactive,non-replicating, Plasmodium falciparum sporozoite (PfSPZ) vaccine (PfSPZ Vaccine) in malaria-naive healthy adults following multiple-dose IV administration.

    Measured: The period of follow-up for each vaccinated subject is through at least 24 weeks after the last vaccination.

  2. To evaluate the safety and tolerability of the metabolicallyactive,non-replicating, Plasmodium falciparum sporozoite(PfSPZ) vaccine (PfSPZ Vaccine) in malaria-naive healthyadults following multiple-dose IM administration.

    Measured: The period of follow-up for each vaccinated subject is through at least 24 weeks after the last vaccination.

  3. To determine if there is PfSPZ Vaccine-mediated protectionagainst infectious P. falciparum CHMI when the vaccine isadministered at 2.7 x 105 PfSPZ per injection by the IV routeusing a multi-dose schedule and the CHMI is administered at@...

    Measured: At 4 weeks after CHMI.

Secondary outcomes (3)
  1. To determine if there is durability of PfSPZ Vaccine-mediatedprotection against infectious P. falciparum CHMI when the vaccine isadministered at 2.7 x 105 PfSPZ per injection by the IV route using amulti-dose schedule and the CHMI is ad...

    Measured: At 4 weeks after CHMI.

  2. To determine if there is PfSPZ Vaccine-mediated protection againstinfectious P. falciparum CHMI when the vaccine is administered at 2.2x 106 PfSPZ per injection by the IM route using a multi-dose schedule and the CHMI is administered at 2-...

    Measured: At 4 weeks after CHMI.CHMI.

  3. To determine if there is durability of PfSPZ Vaccine-mediatedprotection against infectious P. falciparum CHMI when the vaccine isadministered at 2.2 x 106 PfSPZ per injection by the IM route using a multi-dose schedule and the CHMI is admi...

    Measured: At 4 weeks after CHMI.CHMI.

Timeline

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

  1. First posted19 Dec 2013 (estimated)
  2. Study start12 Dec 2013
  3. Primary completion1 May 2015
  4. Study completion8 Sep 2016

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
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
141 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02015091
Sponsor's protocol ID
140035
Other IDs
14-I-0035
Status last verified
8 Sep 2016
First submitted
18 Dec 2013
Last updated
17 Dec 2019
Results posted
No

Publications

  • Nussenzweig RS, Vanderberg J, Most H, Orton C. Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei. Nature. 1967 Oct 14;216(5111):160-2. doi: 10.1038/216160a0. No abstract available.

    PubMed 6057225
  • Seder RA, Chang LJ, Enama ME, Zephir KL, Sarwar UN, Gordon IJ, Holman LA, James ER, Billingsley PF, Gunasekera A, Richman A, Chakravarty S, Manoj A, Velmurugan S, Li M, Ruben AJ, Li T, Eappen AG, Stafford RE, Plummer SH, Hendel CS, Novik L, Costner PJ, Mendoza FH, Saunders JG, Nason MC, Richardson JH, Murphy J, Davidson SA, Richie TL, Sedegah M, Sutamihardja A, Fahle GA, Lyke KE, Laurens MB, Roederer M, Tewari K, Epstein JE, Sim BK, Ledgerwood JE, Graham BS, Hoffman SL; VRC 312 Study Team. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science. 2013 Sep 20;341(6152):1359-65. doi: 10.1126/science.1241800. Epub 2013 Aug 8.

    PubMed 23929949
  • Epstein JE, Tewari K, Lyke KE, Sim BK, Billingsley PF, Laurens MB, Gunasekera A, Chakravarty S, James ER, Sedegah M, Richman A, Velmurugan S, Reyes S, Li M, Tucker K, Ahumada A, Ruben AJ, Li T, Stafford R, Eappen AG, Tamminga C, Bennett JW, Ockenhouse CF, Murphy JR, Komisar J, Thomas N, Loyevsky M, Birkett A, Plowe CV, Loucq C, Edelman R, Richie TL, Seder RA, Hoffman SL. Live attenuated malaria vaccine designed to protect through hepatic CD8(+) T cell immunity. Science. 2011 Oct 28;334(6055):475-80. doi: 10.1126/science.1211548. Epub 2011 Sep 8.

    PubMed 21903775

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PfSPZ Vaccine in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites 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 21 inclusion and 16 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 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

To evaluate the safety and tolerability of the metabolicallyactive,non-replicating, Plasmodium falciparum sporozoite (PfSPZ) vaccine (PfSPZ Vaccine) in malaria-naive healthy adults following multiple-dose IV administration. (time frame: The period of follow-up for each vaccinated subject is through at least 24 weeks after the last vaccination.). 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 NCT02015091, which also lists 3 linked publications.

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 17 Dec 2019.

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