Optimization of Controlled Human Malarial Infection by Injection of P. Falciparum Sporozoites in Non-Immune Adults

This study has been completed.
Sponsor:
Collaborator:
Barcelona Centre for International Health Research
Information provided by (Responsible Party):
Sanaria Inc.
ClinicalTrials.gov Identifier:
NCT01771848
First received: January 8, 2013
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

The study is designed to establish the best dose to safely infect healthy individuals with Plasmodium falciparum sporozoites (PfSPZ) by injection.

The goal of this study is to achieve infections in human volunteers with infection rates of 100% and pre-patent periods of less than 12 days.


Condition Intervention Phase
Malaria
Biological: PfSPZ Challenge
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: A Study to Optimize Controlled Human Malarial Infection by Injection of Plasmodium Falciparum Sporozoites in Non-Immune Adults

Resource links provided by NLM:


Further study details as provided by Sanaria Inc.:

Primary Outcome Measures:
  • Infectivity of the administration regimens [ Time Frame: Study day 6 to day 90 post challenge ] [ Designated as safety issue: No ]
    For each trial stage (A and B) the infectivity of the three administration regimens will be assessed by thick film microscopy and q-PCR for P. falciparum DNA. The time from parasite inoculation to first detection of blood stage parasitemia will be assessed by thick blood film microscopy.


Secondary Outcome Measures:
  • Safety of PfSPZ Challenge [ Time Frame: All study visits until day 90 post challenge ] [ Designated as safety issue: Yes ]
    The safety of PfSPZ Challenge and the resultant P. falciparum infection will be assessed by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements.


Other Outcome Measures:
  • Parasite multiplication rates using qPCR for P. falciparum DNA [ Time Frame: Samples taken at pre-determined timepoints upto 8 months ] [ Designated as safety issue: No ]
    The dynamics of P. falciparum parasite growth following administration of PfSPZ Challenge is assessed by analyzing parasite multiplication rates using qPCR for P. falciparum DNA. Measurements will be used to model parasite kinetics and to estimate the number of infected liver cells. A mathematical model will also be built to describe infection dynamics, parasite distribution, circulation time and parasite turn-over

  • Cellular and humoral immune responses against parasites [ Time Frame: Samples taken at pre-determined timepoints upto 8 months ] [ Designated as safety issue: No ]
    Cellular and humoral immune responses against parasites are assessed by transcriptional RNA analysis, multiparameter flow cytometry, ELIspot, luminex assays, protein arrays, IFA, and ELISA.

  • Stage specific expression patterns of parasite genes [ Time Frame: Samples taken at pre-determined timepoints upto 8 months ] [ Designated as safety issue: No ]
    Stage specific expression patterns of parasite genes is assessed by RNA quantification using reverse transcriptase PCR (rtPCR) and transcriptional profiling on microarray and sequencing platforms,specifically, the presence of mRNA transcripts specific of gametocytes, the pattern of variant gene transcription and adhesion, and the expression of merozoite invasion genes/proteins.


Enrollment: 36
Study Start Date: December 2012
Study Completion Date: July 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Grp 1-10ul x 2; 2,500 PfSPZ Challenge-Part A

PART A:

Group 1 (n=6): 2,500 PfSPZ administered IM in a volume of 10 µL in 2 sites (one injection of 10µL containing 1,250 PfSPZ in each deltoid).

Biological: PfSPZ Challenge
Aseptic, purified, vialed, cryopreserved fully infectious NF54 P. falciparum sporozoites
Experimental: Grp 2-50ul x 2; 2,500 PfSPZ Challenge-Part A

PART A:

Group 2 (n=6): 2,500 PfSPZ administered IM in a volume of 50 µL in 2 sites (one injection of 50µL containing 1,250 PfSPZ in each deltoid).

Biological: PfSPZ Challenge
Aseptic, purified, vialed, cryopreserved fully infectious NF54 P. falciparum sporozoites
Experimental: Grp 3-250ul x 2; 2,500 PfSPZ Challenge-Part A

PART A:

Group 3 (n=6): 2,500 PfSPZ administered IM in a volume of 250 µL in 2 sites (one injection of 250 µL containing 1,250 PfSPZ in each deltoid).

Biological: PfSPZ Challenge
Aseptic, purified, vialed, cryopreserved fully infectious NF54 P. falciparum sporozoites
Experimental: Grp 4-50ul x 2; 25,000 PfSPZ Challenge, Part B

PART B: BEGINS AFTER COMPLETION OF PART A

Group 4 (n=6) (control group) 25,000 PfSPZ administered IM in a volume of 50 µL in 2 sites (one injection of 50 µL containing 12,500 PfSPZ in each deltoid).

Biological: PfSPZ Challenge
Aseptic, purified, vialed, cryopreserved fully infectious NF54 P. falciparum sporozoites
Experimental: Grp 5-Optimal vol Part A x 2; 25,000 PfSPZ Challenge, Part B

PART B: BEGINS AFTER COMPLETION OF PART A

Group 5 (n=6) 25,000 PfSPZ administered IM in the optimum volume determined in Part A in 2 sites (one injection of the optimum volume containing 12,500 PfSPZ in each deltoid).

If the optimal volume in Part A is 50µL, then Group 5 will be modified to avoid duplication of regimens between groups 4 and 5. In this case, volunteers in group 5 will be administered a dose of 25,000 PfSPZ administered intradermally in four 10 µL injections. (Every volunteer will receive 4 ID injections of 6,250 PfSPZ in a volume of 10 µL each, with 2 injections in each arm respectively).

Biological: PfSPZ Challenge
Aseptic, purified, vialed, cryopreserved fully infectious NF54 P. falciparum sporozoites
Experimental: Grp 6-Optimal vol Part A x 2; 125,000* PfSPZ Challenge, Part B

PART B: BEGINS AFTER COMPLETION OF PART A

Group 6 (n=6) 125,000 PfSPZ administered IM in the optimum volume determined in Part A in 2 sites (one injection of the optimum volume containing 62,500 PfSPZ in each deltoid) if the volume is 50 µL or 250 µL.

*If the optimal volume in Part A is 10 µL, then Group 6 will receive 100,000 PfSPZ (2 inoculations of 50,000 PfSPZ) instead of 125,000 PfSPZ.

Biological: PfSPZ Challenge
Aseptic, purified, vialed, cryopreserved fully infectious NF54 P. falciparum sporozoites

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adults aged 18 to 45 years
  • Able and willing (in the Investigator's opinion) to comply with all study requirements
  • Women only: must agree to practice continuous effective contraception for the duration of the study (such as hormonal contraceptives, condom or intrauterine device (IUD)).
  • Agreement to refrain from blood donation in Spain during the course of the study and thereafter
  • Agree not to participate in another study with an investigational product during the course of this study
  • Written informed consent to undergo CHMI
  • Reachable (24/7) by mobile phone during the whole study period
  • Willingness to take a curative anti-malarial regimen
  • Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required
  • Answer all questions on the informed consent quiz correctly
  • A body mass index < 35

Exclusion Criteria:

  • History of P. falciparum malaria
  • Travel to malaria endemic region before the participation in the study with positive P. falciparum serology at screening.
  • Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin)
  • Is using and intends to continuing using a medication known to cause drug reactions with chloroquine or Malarone®, such as cimetidine, metoclopramide, antacids or kaolin (antacids and kaolin can be administered at least 4 hours from intake of chloroquine)
  • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
  • Prior receipt of an investigational malaria vaccine
  • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
  • Use of immunoglobulins or blood products within 3 months prior to enrolment
  • Presence of sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait
  • Pregnancy, lactation or intention to become pregnant during the study
  • A history of allergic disease or reactions likely to be exacerbated by malaria
  • Contraindications or known allergy to the first-line anti-malarial medications: chloroquine, atovaquone/proguanil and artemether/lumefantrine.
  • History of cancer (except successfully treated and cured basal cell carcinoma of the skin and cervical carcinoma in situ)
  • History of serious psychiatric condition that may affect participation in the study
  • Any other serious chronic illness requiring hospital specialist supervision
  • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 30g (men) or 20g (women) per day
  • Suspected or known injecting drug abuse in the 5 years preceding enrolment
  • Seropositive for hepatitis B surface antigen (HBsAg)
  • Seropositive for hepatitis C virus (antibodies to HCV)
  • An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system [42]
  • Abnormal electrocardiogram on screening: pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, non-sinus rhythm except isolated premature atrial contractions, right or left bundle branch block, advanced A-V heart block (secondary or tertiary)
  • Volunteers unable to be closely followed for social, geographic or psychological reasons
  • Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination
  • Any other significant disease, disorder or finding which, in the opinion of the Investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01771848

Locations
Spain
CRESIB, Hospital Clínic-Universitat de Barcelona
Barcelona, Spain, 08036
Centre d'Investigació del Medicament Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Sponsors and Collaborators
Sanaria Inc.
Barcelona Centre for International Health Research
Investigators
Principal Investigator: Pedro L Alonso, MD, Ph.D. Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona
  More Information

No publications provided

Responsible Party: Sanaria Inc.
ClinicalTrials.gov Identifier: NCT01771848     History of Changes
Other Study ID Numbers: BACHMI-01
Study First Received: January 8, 2013
Last Updated: January 31, 2014
Health Authority: United States: Food and Drug Administration
Spain: Departament de Salut de la Generalitat de Catalunya

Keywords provided by Sanaria Inc.:
Malaria
Plasmodium falciparum

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on April 15, 2014