Comparison of Three Plasmodium Falciparum Isolates in a Controlled Human Malaria Infection

NCT01627951 | Completed DMC

• 1 other identifier: TIP3
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

An effective vaccine against malaria is urgently needed to combat the scourge of this disease. Before candidate vaccines can be tested in endemic countries, they are first tested in human volunteers in so-called Controlled Human Malaria Infections (CHMI's). Ideally, a candidate vaccine should be tested against multiple strains of malaria, representative of the disease's global distribution. To date, however, only one such strain (NF54) has been broadly used in CHMI's. The purpose of this study is to compare the course of infections with 2 novel malaria strains to those with NF54 in human volunteers.

Conditions

Malaria

Keywords

Plasmodium falciparum; malaria

Outcome Measures

Primary Outcomes (1)

• Difference in kinetics of infection between groups infected with NF54, NF133 and NF166, as defined by a mathematical model that takes into account multiple measurements of parasitaemia

  Parasitaemia will be measured retrospectively by QRT-PCR in twice daily drawn venous whole blood, from day 5 post-infection until day of thick smear positivity, or else until day 21 post-infection if volunteers have not yet developed a positive thick smear before then. All these data points will be fed into a mathematical model that amalgamates them to calculate an outcome variable with one single value for burden of (liver-stage) infection and one for (blood-stage) multiplication factor.

  between day 5 and day 21

Secondary Outcomes (4)

• Difference in time till thick smear positivity between groups infected with NF54, NF135 and NF166

  between day 5 and day 21

• Difference in duration or peak height of parasitaemia between groups infected with NF54, NF135 and NF166

  between day 5 and day 21

• Difference in frequency of malaria-related symptoms and signs between groups infected with NF54, NF135 and NF166

  between day 5 and day 35

• Difference in induced immunological responses between groups infection with NF54, NF135 and NF166

  between day -1 and day 35

Study Arms (3)

NF54

ACTIVE COMPARATOR

Volunteers will be infected with the NF54 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

Other: NF54

NF135

EXPERIMENTAL

Volunteers will be infected with the NF135 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

Other: NF135

NF166

EXPERIMENTAL

Volunteers will be infected with the NF166 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

Other: NF166

Interventions

NF54 OTHER

Volunteers will be infected with the NF54 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

NF54

NF135 OTHER

Volunteers will be infected with the NF135 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

NF135

NF166 OTHER

Volunteers will be infected with the NF166 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

NF166

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• year-old healthy volunteers (males and females)
• General good health based on history,clinical examination and basic haematology and biochemistry results
• Negative pregnancy test in females
• Use of adequate contraception for females
• All volunteers must sign the informed consent form following proper understanding of the design and procedures of the study
• Volunteer agrees to inform his/her general practitioner and agrees to sign a request for medical information concerning possible contra-indications for participation in the study
• Willingness to undergo a Plasmodium falciparum sporozoite challenge
• Agreement to stay in a hotel room close to the trial center during a part of the study (day 5 post-infection until three days after initiation of treatment)
• Reachable by mobile phone during the whole study period
• Available to attend all study visits
• Agreement to refrain from blood donation to (Sanquin) blood bank or for other purposes, during the course of the study and for a minimum of three years thereafter
• Willingness to undergo an HIV, HBV and HCV test
• Negative urine toxicology screening test at screening visit and on the 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 P. falciparum
• Symptoms, physical signs and laboratory values suggestive of systemic disorders, including but not limited to 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 volunteer during infection
• History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
• Clinically significant ECG abnormalities at screening, or history of arrhythmia's or prolonged QT-interval
• Positive family history of cardiac disease in 1st or 2nd degree relatives \<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 30kg/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 during or within 30 days prior to the onset of the trial
• Pregnant or lactating women
• Volunteers unable to give written informed consent
• Volunteers unable to be closely followed for social, geographic or psychological reasons

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Havenziekenhuis: collaborator

Study Sites (2)

UMC St Radboud

Nijmegen, Netherlands

Location

Havenziekenhuis

Rotterdam, Netherlands

Location

Related Publications (1)

• McCall MBB, Wammes LJ, Langenberg MCC, van Gemert GJ, Walk J, Hermsen CC, Graumans W, Koelewijn R, Franetich JF, Chishimba S, Gerdsen M, Lorthiois A, van de Vegte M, Mazier D, Bijker EM, van Hellemond JJ, van Genderen PJJ, Sauerwein RW. Infectivity of Plasmodium falciparum sporozoites determines emerging parasitemia in infected volunteers. Sci Transl Med. 2017 Jun 21;9(395):eaag2490. doi: 10.1126/scitranslmed.aag2490.

  PMID: 28637923 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Perry van Genderen, MD PhD

  Havenziekenhuis

  PRINCIPAL INVESTIGATOR

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
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2012
• First Posted: June 26, 2012
• Study Start: August 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 27, 2012

Record last verified: 2012-11

Locations

NL (2)