A Clinical Trial to Evaluate Plasmodium Falciparum 7G8 and NF54 Challenge Strains (PfSPZ) in a Head-to-head Comparative Study - (ECG-CHMI) (ECG-CHMI)

A Phase 1 Clinical Trial To Evaluate The Safety and Infectivity Of Direct Venus Inoculation of Aseptic, Purified, Cryopreserved Plasmodium Falciparum 7G8 And NF54 Challenge Strains (PfSPZ) in a Head-To-Head Comparative Study

A comparison of Malaria events (symptoms and signs of malaria) experienced by subjects infected with PfSPZ Challenge (NF54) vs. PfSPZ Challenge (7G8).

Study Overview

Status

Withdrawn

Intervention / Treatment

Detailed Description

The single center study is designed as a double-blind, randomized, placebo-controlled CHMI trial with 2 parallel test groups to directly compare clinical and laboratory characteristics of the NF54 and 7G8 strains of PfSPZ Challenge. This study will also evaluate signatures of and time to parasitemia by multiple methods and evaluate physiologic status data collected by non-invasive wearable monitors before and during Plasmodium falciparum infection to characterize and trend physiologic changes appearing prior to the onset of parasitemia.

PfSPZ Challenge (aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites) or normal saline will be administered by direct venous inoculation (DVI) by 25-gauge needle and syringe to healthy malaria naïve adults.

Data generated from samples collected for biomarker assay analysis will be useful for developing predictive models to evaluate the efficacy of malaria vaccine candidates.

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adults (male or non-lactating, non-pregnant female)
  • Between the ages of 18 and 45 (inclusive) at the time of enrollment
  • Body weight equal to or greater than 110 lbs
  • Available and willing to participate for duration of study
  • Able and willing to provide a written informed consent
  • Able to complete an Assessment of Understanding with a score of at least 80% correct
  • In good general health with no clinically significant health problems as established by medical history, physical examination, and laboratory screening
  • Sexually active females, unless surgically sterile or at least 1 year post-menopausal, must use an effective method of avoiding pregnancy (Section 5.4.5.3) from 14 days prior to CHMI and agree to continue using such precautions during the study until at least 2 months after CHMI
  • If female subjects are unable to bear children due to menopause or have had a procedure performed (e.g. tubal ligation or hysterectomy), a medical note from a physician is required
  • If post-menopausal, subjects must have experienced at least 1 year of amenorrhea and provide a medical note from her physician documenting this medical history
  • Agree not to travel to a malaria endemic area during the course of the study
  • Agree to refrain from blood donation from the time of CHMI and for 3 years following CHMI
  • Must be willing to take anti-malarial treatment after CHMI
  • Must agree to stay in a pre-determined hotel near the NMRC CTC from approximately 7 days after CHMI until antimalarial treatment is completed or through 18 days post CHMI
  • For active-duty military personnel, documentation of their command's approval to participate

Exclusion Criteria:

  • Pregnant (positive urine pregnancy test) or nursing at screening or plans to become pregnant or nurse at any period from the time of enrollment through 56 days after CHMI.
  • Receipt of any investigational malaria vaccine
  • Any history of malaria infection
  • Travel to a malaria endemic region within 6 months of enrollment or during the study (from enrollment through 2 months after CHMI)
  • History of long-term residence (>5 years) in an area known to have significant transmission of P falciparum (http://www.cdc.gov/malaria/map/)
  • History of clinically significant contact dermatitis
  • Seropositive for the human immunodeficiency virus (HIV), hepatitis C virus (HCV), and/or hepatitis B surface antigen (HBsAg)
  • Positive sickle cell screening test, including evidence of sickle cell trait or sickle cell anemia (due to its effect on subject's susceptibility to malaria)
  • History of thalassemia or thalassemia trait (due to its effect on subject's susceptibility to malaria)
  • Participation in any clinical study involving another investigational vaccine, drug, or other products within 60 days prior to enrollment or plan to participate in such a clinical study during or within 1 month following the active study phase of the study (from the day enrollment through 2 months after CHMI)
  • Allergy to any component of the PfSPZ Challenge formulation, Malarone® (atovaquone-proguanil), and/or Coartem® (artemether-lumefantrine)
  • History of porphyria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group 1 - PfSPZ, (NF54) strain
Group 1 (N=9) will receive PfSPZ Challenge (NF54) A one-time dose of 3,200 aseptic, purified, cryopreserved, non-attenuated Plasmodium falciparum (Pf) NF54 sporozoites (Pf SPZ Challenge) Mode of administration: Direct venous inoculation (DVI) through a 25 gauge needle and syringe
Malaria standard treatment regimen
Other Names:
  • artemether/lumefantrine (AL; Coartem)
Active Comparator: Group 2 - PfSPZ, (7G8) strain
Group 2 (N=9) will receive PfSPZ Challenge (7G8) A one-time dose of 3,200 aseptic, purified, cryopreserved, non-attenuated Plasmodium falciparum 7G8 sporozoites (Pf SPZ Challenge) Mode of administration: Direct venous inoculation (DVI) through a 25 gauge needle and syringe
Malaria standard treatment regimen
Other Names:
  • artemether/lumefantrine (AL; Coartem)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in the pre-patent period
Time Frame: 29 days
The difference in the time of first malaria event (symptom or sign of malaria),in subjects infected with PfSPZ Challenge (NF54) vs. PfSPZ Challenge (7G8)
29 days
Difference in the total number of malaria events
Time Frame: 29 days
The difference in the total number of Grade 2 or greater malaria events (symptoms and signs of malaria) experienced by subjects infected with PfSPZ Challenge (NF54) vs PfSPZ Challenge (7G8)
29 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine differences in pre-patent periods
Time Frame: 29 days
Determine differences in prepatent periods in subjects infected with PfSPZ Challenge (NF54) vs PfSPZ Challenge (7G8) as detected by TBS, RDT, hsRDT and by PCR
29 days
Determine differences in the growth rate of parasites
Time Frame: 29 days
Determine differences in the growth rate of parasites in the blood of subjects infected by PfSPZ Challenge (NF54) vs PfSPZ Challenge (7G8) as detected by PCR
29 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 1, 2020

Primary Completion (Anticipated)

June 1, 2021

Study Completion (Anticipated)

September 1, 2021

Study Registration Dates

First Submitted

December 16, 2019

First Submitted That Met QC Criteria

December 16, 2019

First Posted (Actual)

December 18, 2019

Study Record Updates

Last Update Posted (Actual)

May 8, 2020

Last Update Submitted That Met QC Criteria

May 6, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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