MalariaTIP3NCT01627951
Comparison of Three Plasmodium Falciparum Isolates in a Controlled Human Malaria Infection
A study testing NF54, NF135 and NF166 in people with Malaria, run by Radboud University Medical Center at 2 sites in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- NF54, NF135 and NF166
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesNetherlands
- Study dates
- Aug 2012to Nov 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-35 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
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- 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®
Who cannot join
- 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
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- 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
- Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study
- A history of psychiatric disease or convulsions
- Known hypersensitivity to anti-malarial drugs
- History of severe reactions or allergy to mosquito bites
- The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months before study onset (inhaled and topical corticosteroids are allowed) or during the study period
- Contra-indications for Malarone® use including treatment taken by the volunteers that interfere with Malarone®
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia
- Co-workers of the department of Medical Microbiology of the UMC St Radboud or Havenziekenhuis, Rotterdam
- A history of sickle cell, thalassaemia trait and G6PD deficiency
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Comparison of NF54, NF135 and NF166 Strains of Plasmodium Falciparum in a Controlled Human Malaria Infection (TIP3)
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.
Read the detailed description
Plasmodium falciparum (Pf) malaria remains responsible for an intolerable burden of morbidity worldwide and an effective vaccine is sorely needed to aid control efforts. Before candidate malaria vaccines can enter full-scale (phase IIb) field trials in endemic areas, they must first be tested under controlled circumstances in (phase IIa) clinical human malaria infection studies. Since Pf isolates display a wide genetic diversity across the globe, phase IIa challenge infections should be conducted with both homologous and heterologous strains.
Since 1998 a highly successful Controlled Human Malaria Infection model at the UMC St Radboud, Nijmegen, The Netherlands, has been employed both to test candidate vaccines and to answer fundamental questions about pathophysiological and immunological mechanisms during early Pf infection in human volunteers. To date largely the NF54 strain of P. falciparum has been used in this Nijmegen model, with which extensive experience has meanwhile been acquired. In order to increase the portfolio of Pf strains available for future phase IIa studies, it is first necessary to document in detail the parasitological, clinical and immunological characteristics of new candidate strains during a controlled human malaria infection. In this study, the strains NF135 and NF166 will be compared in this regard with the well-characterised NF54 strain.
- Conditions
- Malaria
- Being tested
- NF54, NF135, NF166
- Keywords
- Plasmodium falciparum, malaria
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NF54Other
Volunteers will be infected with the NF54 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.
NF135Other
Volunteers will be infected with the NF135 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.
NF166Other
Volunteers will be infected with the NF166 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.
| Study group | Role | What they receive |
|---|---|---|
| NF54 | Active comparator | Volunteers will be infected with the NF54 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes. Receives: Other: NF54 |
| NF135 | Experimental | Volunteers will be infected with the NF135 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes. Receives: Other: NF135 |
| NF166 | Experimental | Volunteers will be infected with the NF166 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes. Receives: Other: NF166 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: between day 5 and day 21
Secondary outcomes (4)
Difference in time till thick smear positivity between groups infected with NF54, NF135 and NF166
Thick smears will be read twice daily from day 5 post-infection until day of thick smear positivity, or else until day 21 post-infection
Measured: between day 5 and day 21
Difference in duration or peak height of parasitaemia between groups infected with NF54, NF135 and NF166
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.
Measured: between day 5 and day 21
Difference in frequency of malaria-related symptoms and signs between groups infected with NF54, NF135 and NF166
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 24 post-infection, and then again on day 35-post infection.
Measured: between day 5 and day 35
Difference in induced immunological responses between groups infection with NF54, NF135 and NF166
Peripheral venous whole blood will be drawn for assessment of serological and cellular immune responses on day 1-prior to infection, day 5 post-infection, day 9 post-infection and day 35 post-infection.
Measured: between day -1 and day 35
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2012 (estimated)
- Study startAug 2012
- Primary completionOct 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Havenziekenhuis
- Responsible party
- Sponsor
- Investigators
- Perry van Genderen, MD PhD, Principal investigator, Havenziekenhuis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01627951
- Sponsor's protocol ID
- TIP3
- Acronym
- TIP3
- Status last verified
- Nov 2012
- First submitted
- 25 May 2012
- Last updated
- 27 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 28637923
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of NF54, NF135 and NF166 Strains of Plasmodium Falciparum in a Controlled Human Malaria Infection (TIP3)
- ClinicalTrials.gov ID
- NCT01627951
- Acronym / sponsor ID
- TIP3 / TIP3
- Conditions
- Malaria
- Keywords
- Plasmodium falciparum, malaria
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Havenziekenhuis
- Study start
- Aug 2012
- Primary completion
- Oct 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 26 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Plasmodium falciparum (Pf) malaria remains responsible for an intolerable burden of morbidity worldwide and an effective vaccine is sorely needed to aid control efforts. Before candidate malaria vaccines can enter full-scale (phase IIb) field trials in endemic areas, they must first be tested under controlled circumstances in (phase IIa) clinical human malaria infection studies. Since Pf isolates display a wide genetic diversity across the globe, phase IIa challenge infections should be conducted with both homologous and heterologous strains.
Since 1998 a highly successful Controlled Human Malaria Infection model at the UMC St Radboud, Nijmegen, The Netherlands, has been employed both to test candidate vaccines and to answer fundamental questions about pathophysiological and immunological mechanisms during early Pf infection in human volunteers. To date largely the NF54 strain of P. falciparum has been used in this Nijmegen model, with which extensive experience has meanwhile been acquired. In order to increase the portfolio of Pf strains available for future phase IIa studies, it is first necessary to document in detail the parasitological, clinical and immunological characteristics of new candidate strains during a controlled human malaria infection. In this study, the strains NF135 and NF166 will be compared in this regard with the well-characterised NF54 strain.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NF54 | Active comparator | Other: NF54Volunteers will be infected with the NF54 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes. |
| NF135 | Experimental | Other: NF135Volunteers will be infected with the NF135 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes. |
| NF166 | Experimental | Other: NF166Volunteers will be infected with the NF166 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- 18-35 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
Key exclusion criteria (24 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NF54Volunteers will be infected with the NF54 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes. | Other | NF54 |
| NF135Volunteers will be infected with the NF135 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes. | Other | NF135 |
| NF166Volunteers will be infected with the NF166 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes. | Other | NF166 |
Primary outcome
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
Time frame: between day 5 and day 21
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.
4 secondary outcomes
Difference in time till thick smear positivity between groups infected with NF54, NF135 and NF166
Time frame: between day 5 and day 21
Difference in duration or peak height of parasitaemia between groups infected with NF54, NF135 and NF166
Time frame: between day 5 and day 21
Difference in frequency of malaria-related symptoms and signs between groups infected with NF54, NF135 and NF166
Time frame: between day 5 and day 35
Difference in induced immunological responses between groups infection with NF54, NF135 and NF166
Time frame: between day -1 and day 35
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2012.
- Derived from this study: PubMed 28637923McCall 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Perry van Genderen, MD PhD principal investigator
Havenziekenhuis
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NF54, NF135 and NF166 in people with Malaria, run by Radboud University Medical Center at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: between day 5 and day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01627951, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2012.