NCT01001650

Brief Summary

The purpose of this study is to determine the safety and tolerability of a non-replicating, metabolically active Plasmodium falciparum sporozoite (PfSPZ) vaccine in malaria-naïve healthy volunteers following multiple-dose subcutaneous (SC) or intradermal (ID) administration. In addition, the investigators wish to evaluate PfSPZ vaccine-mediated protection against P. falciparum challenge in the following 4 groups (see below) and compare protective efficacy of the PfSPZ vaccine when given by SC v ID administration in all these groups:

  • Group 1: 4 doses of 7,500 PfSPZ/immunization,
  • Group 2: 4 doses of 30,000 PfSPZ/immunization,
  • Group 3: 4 doses of 135,000 PfSPZ/immunization
  • Group 4: 4 or 6 doses of 135,000 PfSPZ/immunization. If \> 80% protective efficacy is not achieved in Groups 1, 2, or 3, volunteers in Group 4 will receive a fifth and sixth dose.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Apr 2009

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2009

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

October 22, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 26, 2009

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2010

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2010

Completed
Last Updated

September 10, 2014

Status Verified

September 1, 2014

Enrollment Period

1.2 years

First QC Date

October 22, 2009

Last Update Submit

September 9, 2014

Conditions

Keywords

Malaria VaccinePlasmodium falciparum

Outcome Measures

Primary Outcomes (1)

  • To determine the safety and tolerability of a non-replicating, metabolically active Plasmodium falciparum sporozoite (PfSPZ) vaccine in malaria-naïve healthy volunteers following multiple-dose subcutaneous (SC) or intradermal (ID) administration.

    October 2010

Secondary Outcomes (2)

  • To evaluate PfSPZ vaccine-mediated protection against P. falciparum challenge in the 4 groups.

    October 2010

  • To compare protective efficacy of the PfSPZ vaccine when given by SC versus ID administration in all groups.

    October 2010

Study Arms (4)

Group 1

EXPERIMENTAL

4 doses of 7,500 PfSPZ/immunization.

Biological: Plasmodium falciparum Sporozoite (strain NF-54; Anopheles stephensi mosquitoes) Vaccine, Live, Inactivated (gamma irradiation)

Group 2

EXPERIMENTAL

4 doses of 30,000 PfSPZ/immunization

Biological: Plasmodium falciparum Sporozoite (strain NF-54; Anopheles stephensi mosquitoes) Vaccine, Live, Inactivated (gamma irradiation)

Group 3

EXPERIMENTAL

4 doses of 135,000 PfSPZ/immunization

Biological: Plasmodium falciparum Sporozoite (strain NF-54; Anopheles stephensi mosquitoes) Vaccine, Live, Inactivated (gamma irradiation)

Group 4

EXPERIMENTAL

4 or 6 doses of 135,000 PfSPZ/immunization.

Biological: Plasmodium falciparum Sporozoite (strain NF-54; Anopheles stephensi mosquitoes) Vaccine, Live, Inactivated (gamma irradiation)

Interventions

Group 1: 4 doses of 7,500 PfSPZ/immunization, Group 2: 4 doses of 30,000 PfSPZ/immunization, Group 3: 4 doses of 135,000 PfSPZ/immunization, and Group 4: 4 or 6 doses of 135,000 PfSPZ/immunization. If \> 80% protective efficacy is not achieved in Groups 1, 2, or 3, volunteers in Group 4 will receive a fifth and sixth dose.

Group 1Group 2Group 3Group 4

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy adults (male or non-pregnant female) 18-50 years of age, inclusive.
  • Able and willing to participate for the duration of the study.
  • Able and willing to provide written (not proxy) informed consent.
  • Women of childbearing potential must agree to use effective means of birth control through the duration of the study.
  • Willing to refrain from blood donation (except as required in this study) for 3 years following P. falciparum challenge.
  • Agree not to travel to a malaria endemic region during the entire course of the trial.

You may not qualify if:

  • Any history of malaria infection, or travel to a malaria endemic region within 6 months prior to first immunization.
  • History of long term residence (\>5 years) in area known to have significant transmission of P. falciparum.
  • Positive HIV, HBsAg or HCV serology. Positive sickle cell screening test.
  • Has evidence of increased cardiovascular disease risk (defined as \> 10%, 5 year risk) as determined by the method of Gaziano (Gaziano 2008). Risk factors include sex, age (years), systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/mm2), reported diabetes status, and blood pressure.
  • Current use of systemic immunosuppressant pharmacotherapy.
  • An abnormal EKG, defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block.
  • Current significant medical condition (cardiovascular, hepatic, renal, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination.
  • History of a splenectomy.
  • History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the volunteer's participation in the protocol or compromise the scientific objectives. This may include psychiatric disorders (such as personality disorders, anxiety disorders, or schizophrenia) or behavioral tendencies (including active alcohol or drug abuse) discovered during the screening process that in the opinion of the investigator would make compliance with the protocol difficult.
  • Plan for surgery between enrollment and challenge.
  • Females who are pregnant or nursing, females who plan on becoming pregnant or plan to nurse during the study period.
  • Known allergy to any component of the vaccine formulation, history of anaphylactic response to mosquito bites, retinal or visual field changes, or known allergy to the anti-malarial chloroquine phosphate, which will be used to treat volunteers developing malaria after P. falciparum challenge.
  • Participation in any study involving another investigational vaccine or drug within 90 days prior to the screening visit, or plan to participate in another investigational vaccine/drug research during or within 1 month following participation in this 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 immunization or challenge.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

The Center for Vaccine Development, University of Maryland (CVD/UMB)

Baltimore, Maryland, 21201, United States

Location

Naval Medical Research Center (NMRC) Clinical Trials Center, on the campus of the National Naval Medical Center (NNMC)

Bethesda, Maryland, 20889-5607, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Vaccines

Condition Hierarchy (Ancestors)

MalariaProtozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

Biological ProductsComplex Mixtures

Study Officials

  • Judith E Epstein, M.D.

    Naval Medical Research Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 22, 2009

First Posted

October 26, 2009

Study Start

April 1, 2009

Primary Completion

July 1, 2010

Study Completion

September 1, 2010

Last Updated

September 10, 2014

Record last verified: 2014-09

Locations