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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02149550




Registration number
NCT02149550
Ethics application status
Date submitted
1/11/2014
Date registered
28/05/2014
Date last updated
21/11/2014

Titles & IDs
Public title
Controlled Human Malaria Infection After Bites From Mosquitoes Infected With Two Novel P. Falciparum Strains
Scientific title
Controlled Human Malaria Infection After Bites From Mosquitoes Infected With NF135.C10 or NF166.C8 Plasmodium Falciparum Parasites (BMGF2a)
Secondary ID [1] 0 0
BMGF2a
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - NF135 n=5
Other interventions - NF135 n=2
Other interventions - NF135 n=1
Other interventions - NF166 n=5
Other interventions - NF166 n=2
Other interventions - NF166 n=1

Active Comparator: NF135 n=5 - Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes

Experimental: NF135 n=2 - Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes

Experimental: NF135 n=1 - Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito

Active Comparator: NF166 n=5 - Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes

Experimental: NF166 n=2 - Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes

Experimental: NF166 n=1 - Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito


Other interventions: NF135 n=5
Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

Other interventions: NF135 n=2
Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes.

Other interventions: NF135 n=1
Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito.

Other interventions: NF166 n=5
Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

Other interventions: NF166 n=2
Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes.

Other interventions: NF166 n=1
Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of subjects in each group who develop patent parasitaemia as assessed by QRT-PCR - Parasitaemia will be measured twice daily by QRT-PCR in venous whole blood, from day 5 post-infection until PCR-positive, or else until day 13 post-infection if subjects have not yet developed a positive PCR before then.
Timepoint [1] 0 0
between day 5 and day 13
Secondary outcome [1] 0 0
Time to patent parasitaemia in each group as assessed by QRT-PCR - Parasitaemia will be measured twice daily by QRT-PCR in venous whole blood, from day 5 post-infection until PCR-positive, or else until day 13 post-infection if subjects have not yet developed a positive PCR before then.
Timepoint [1] 0 0
between day 5 and day 13
Secondary outcome [2] 0 0
Magnitude of first peak of parasitaemia in each group as assessed by QRT-PCR - Parasitaemia will be measured twice daily by QRT-PCR in venous whole blood, from day 5 post-infection until PCR-positive, or else until day 13 post-infection if subjects have not yet developed a positive PCR before then.
Timepoint [2] 0 0
between day 5 and day 13
Secondary outcome [3] 0 0
Frequency of malaria-related symptoms and signs in each group - Symptoms and signs will be assessed at twice daily check-up visits from day 5 post-infection until three days after thick smear positivity, or else until day 16 post-infection, and then again on day 35-post infection.
Timepoint [3] 0 0
between day 0 and day 35

Eligibility
Key inclusion criteria
1. Subject is aged ≥ 18 and ≤ 35 years and in good health.

2. Subject has adequate understanding of the procedures of the study and agrees to abide
strictly thereby.

3. Subject is able to communicate well with the investigator, is available to attend all
study visits, lives in proximity to the trial centre (<10 km) or (if >10km) is willing
to stay in a hotel close to the trial centre during part of the study (day five
post-infection until three days post-treatment). Furthermore the subject will remain
within the Netherlands during the study period and is reachable (24/7) by mobile
telephone throughout the entire study period.

4. Subject agrees to inform his/her general practitioner and (if applicable) medical
specialist about participation in the study and to sign a request to release by the GP
any relevant medical information concerning possible contra-indications for
participation in the study.

5. Subject agrees to refrain from blood donation to Sanquin or for other purposes
throughout the study period and for a defined period thereafter according to current
Sanquin guidelines.

6. For female subjects: subject agrees to use adequate contraception and not to
breastfeed for the duration of study.

7. Subject has signed informed consent.
Minimum age
18 Years
Maximum age
35 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any history, or evidence at screening, of clinically significant symptoms, physical
signs or abnormal laboratory values suggestive of systemic conditions, such as
cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine,
malignant, haematological, infectious, immunodeficient, psychiatric and other
disorders, which could compromise the health of the volunteer during the study or
interfere with the interpretation of the study results. These include, but are not
limited to, any of the following:

1.1 Body weight <50 kg or Body Mass Index (BMI) <18.0 or >30.0 kg/m2 at screening 1.2
A heightened risk of cardiovascular disease, defined as: an estimated ten year risk of
fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic
Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically
significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG
abnormalities; or a positive family history of cardiac events in 1st or 2nd degree
relatives <50 years old.

1.3 Functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD
deficiency.

1.4 History of epilepsy in the period of five years prior to study onset, even if no
longer on medication.

1.5 Positive HIV, HBV or HCV screening tests. 1.6 Chronic use of i) immunosuppressive
drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior
to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted)
or expected use of such during the study period.

1.7 History of malignancy of any organ system (other than localized basal cell
carcinoma of the skin), treated or untreated, within the past 5 years 1.8 Any history
of treatment for severe psychiatric disease by a psychiatrist in the past year.

1.9 History of drug or alcohol abuse interfering with normal social function in the
period of one year prior to study onset, or positive urine toxicology test for cocaine
or amphetamines at screening or prior to infection.

2. For female subjects: positive urine pregnancy test at screening or prior to infection.

3. Any history of malaria, positive serology for P. falciparum, or previous participation
in any malaria (vaccine) study.

4. Known hypersensitivity to or contra-indications (including co-medication) for use of
atovaquone-proguanil (Malarone®) or artemether-lumefantrine (Riamet®), or history of
severe (allergic) reactions to mosquito bites.

5. Receipt of any vaccinations in the 3 months prior to the start of the study or plans
to receive any other vaccinations during the study period or up to 8 weeks thereafter.

6. Participation in any other clinical study in the 30 days prior to the start of the
study or during the study period.

7. Being an employee or student of the department of Medical Microbiology of the
Radboudumc, the department of Internal Medicine or Laboratory of the Havenziekenhuis
or the department of Medical Microbiology & Infectious Diseases of the Erasmus MC.

8. Any other condition or situation that would, in the opinion of the investigator, place
the subject at an unacceptable risk of injury or render the subject unable to meet the
requirements of the protocol.

Study design
Purpose of the study
Basic Science
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Netherlands
State/province [1] 0 0
Nijmegen
Country [2] 0 0
Netherlands
State/province [2] 0 0
Rotterdam

Funding & Sponsors
Primary sponsor type
Other
Name
Radboud University
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Havenziekenhuis, Rotterdam
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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. Recently we compared, for the first time, infections with the
novel malaria strains NF135 and NF166 to those with the broadly-used and well-characterised
strain NF54.

The purpose of the current study is to optimise the course of infections with these novel
strains by determining the minimum number of infectious bites necessary to reliably induce a
malaria infection.
Trial website
https://clinicaltrials.gov/show/NCT02149550
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Perry van Genderen, MD, PhD
Address 0 0
Havenziekenhuis
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications