NCT01002833

Brief Summary

Plasmodium falciparum isolates display a wide genetic diversity with possibly different properties to induce immune responses. These properties could directly influence the ability to induce protective efficacy. Since 1998 an experimental human malaria infection model at the Radboud University Nijmegen Medical Center (RUNMC) has been very successful in answering questions with regards to immunological mechanisms of human Pf infection. To date only the NF54 strain of Pf has been deployed in this Nijmegen model. However, investigation of heterologous Pf challenge is not only highly informative for our basic understanding of induction of immune responses but also provides an essential model for protective capacity testing in the clinical development of candidate malaria vaccines. Recently, the parasite culture laboratory of the RUNMC has been able to overcome technical hurdles to produce infectious mosquitoes of two genetically different isolates from different geographical regions to increase the portfolio for Phase IIa trials. These isolates, PfA and PfB will be compared with the NF54 strain for parasitic, immunological and clinical features in humans.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
15

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Apr 2010

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

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

First Submitted

Initial submission to the registry

October 26, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 27, 2009

Completed
5 months until next milestone

Study Start

First participant enrolled

April 1, 2010

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2010

Completed
Last Updated

November 9, 2010

Status Verified

February 1, 2010

Enrollment Period

7 months

First QC Date

October 26, 2009

Last Update Submit

November 8, 2010

Conditions

Plasmodium FalciparumMalaria

Keywords

Plasmodium falciparumMalaria

Outcome Measures

Primary Outcomes (1)

  • A significant difference in kinetics of parasitemia between groups A, B and C

    35 days

Secondary Outcomes (4)

  • Immunological properties of different Plasmodium falciparum isolates

    140 days

  • Time to thick smear positivity between groups A, B and C

    35 days

  • Maximum parasitemia and duration of parasitemia as measured by PCR

    35 days

  • Frequency of signs and symptoms between groups A, B and C

    140 days

Study Arms (3)

PfA

EXPERIMENTAL

Exposure of human volunteers to bites of mosquitoes infected with the A strain of Plasmodium falciparum

Biological: Exposure to Plasmodium falciparum infected mosquitoes

PfB

EXPERIMENTAL

Exposure of human volunteers to bites of mosquitoes infected with the B strain of Plasmodium falciparum

Biological: Exposure to Plasmodium falciparum infected mosquitoes

NF54

ACTIVE COMPARATOR

Exposure of human volunteers to bites of mosquitoes infected with the NF54 strain of Plasmodium falciparum

Biological: Exposure to Plasmodium falciparum infected mosquitoes

Interventions

Exposure to Plasmodium falciparum infected mosquitoesBIOLOGICAL

Healthy volunteers are exposed to the bites of 5 Plasmodium falciparum infected mosquitoes

NF54PfAPfB

Eligibility Criteria

Age18 Years - 35 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Age \> 18 and \< 35 years healthy volunteers (males or females)
  • General good health based on history and clinical examination
  • Negative pregnancy test
  • Use of adequate contraception for females
  • All volunteers have to sign the informed consent form following proper understanding of the meaning and procedures of the study
  • Volunteer agrees to inform the general practitioner and agrees to sign a request for medical information concerning contra-indications for participation in the study
  • Willingness to undergo a Pf sporozoite challenge
  • Agreement to stay in a hotel room close to the trial center during a part of the study (Day 5 till Day T +3)
  • Reachable by mobile phone during the whole study period
  • Available to attend all study visits
  • Agreement to refrain from blood donation to Sanquin or for other purposes, during the course of the study
  • Willingness to undergo an HIV, hepatitis B and C test
  • Negative urine toxicology screening test at screening visit and day before challenge
  • Willingness to take a curative regimen of Malarone®

You may not qualify if:

  • History of malaria
  • Plans to travel to endemic malaria areas during the study period
  • Previous participation in any malaria vaccine study and/or positive serology for Pf
  • Symptoms, physical signs and laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the study results or compromise the health of the volunteers
  • History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
  • History of arrhythmia's or prolonged QT-interval
  • Positive family history in 1st and 2nd degree relatives for cardiac disease \< 50 years old
  • An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system
  • Body Mass Index (BMI) below 18 or above 30 kg/m2
  • Any clinically significant deviation from the normal range in biochemistry or haematology blood tests or in urine analysis
  • Positive HIV, HBV or HCV tests
  • Participation in any other clinical study within 30 days prior to the onset of the study
  • Volunteers enrolled in any other clinical study during the study period
  • Pregnant or lactating women
  • Volunteers unable to give written informed consent
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Leiden University Medical Center

Leiden, 2300 RC, Netherlands

Location

Related Publications (2)

  • Coffeng LE, Hermsen CC, Sauerwein RW, de Vlas SJ. The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection. PLoS Comput Biol. 2017 Jan 12;13(1):e1005255. doi: 10.1371/journal.pcbi.1005255. eCollection 2017 Jan.

    PMID: 28081133DERIVED

  • Teirlinck AC, Roestenberg M, van de Vegte-Bolmer M, Scholzen A, Heinrichs MJ, Siebelink-Stoter R, Graumans W, van Gemert GJ, Teelen K, Vos MW, Nganou-Makamdop K, Borrmann S, Rozier YP, Erkens MA, Luty AJ, Hermsen CC, Sim BK, van Lieshout L, Hoffman SL, Visser LG, Sauerwein RW. NF135.C10: a new Plasmodium falciparum clone for controlled human malaria infections. J Infect Dis. 2013 Feb 15;207(4):656-60. doi: 10.1093/infdis/jis725. Epub 2012 Nov 27.

    PMID: 23186785DERIVED

MeSH Terms

Conditions

Malaria, FalciparumMalaria

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

October 26, 2009

First Posted

October 27, 2009

Study Start

April 1, 2010

Primary Completion

November 1, 2010

Study Completion

November 1, 2010

Last Updated

November 9, 2010

Record last verified: 2010-02

Locations

NL(1)