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MalariaPhase 1/2CHMI-trans1NCT02836002

Controlled Human Malaria Infection Model for Evaluation of Transmission-Blocking Interventions - Study 1

A Phase 1/2 study testing Sulfadoxine-pyrimethamine (low dose), Piperaquine (low dose) and Sulfadoxine-pyrimethamine (high dose) in people with Malaria, run by Radboud University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a single-center, open label study. The primary aim of this project is to develop a controlled human malaria infection transmission model ("CHMI-trans") or "challenge model" to evaluate the capacity of vaccines, biologics (monoclonal antibodies, or mAbs), and drugs to block malaria parasite transmission by… 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?
Sulfadoxine-pyrimethamine (low dose), Piperaquine (low dose) and Sulfadoxine-pyrimethamine (high dose)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteNetherlands
Study dates
Jun 2016to 29 Jun 2017
Phase
Phase 1/2
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

  • In order to be eligible to participate in this study, a subject must meet all of the following criteria:
  • Subject is aged ≥ 18 and ≤ 35 years and in good health.
  • Subject has adequate understanding of the procedures of the study and is able and willing (in the investigator's opinion) to comply with all study requirements.
  • Subject is willing to complete an informed consent questionnaire and is able to answer all questions correctly.
  • Subject is able to communicate well with the investigator and 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 (from day 5 post-infection until DT1+4 provided that the subject has had 2 consecutive negative 18S qPCR tests (at least 24 hours apart) following DT1 treatment; or until day DT2+3).
  • The subject will remain within the Netherlands during the challenge period, will not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period.
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  • Subject agrees to their general practitioner being informed and contacted about their participation in the study and agrees to sign a form to request the release by their General Practitioner (GP), and medical specialist when necessary, to the investigator(s), of any relevant medical information concerning possible contra-indications for participation in the study.
  • The 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.
  • For female subjects: subject agrees to use continuous adequate contraception** and not to breastfeed for the duration of study.
  • Subject agrees to refrain from intensive physical exercise (disproportionate to the subjects usual daily activity or exercise routine) during the malaria challenge period.
  • Subject has signed written informed consent to participate in the trial.
  • (Acceptable forms of contraception include: established use of oral, injected or implanted hormonal contraceptives; intrauterine device or intrauterine system; barrier methods (condoms or diaphragm with additional spermicide); male partner's sterilisation (with appropriate post-vasectomy documentation of absence of sperm in the ejaculate); true abstinence when this is in line with the preferred and usual lifestyle of the subject; Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.)

Who cannot join

  • A potential subject who meets any of the following criteria will be excluded from participation in this study:
  • 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 or >30 kg/m2 at screening. 1.2. A heightened risk of cardiovascular disease, as determined by: 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. A medical history of 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. Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) 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.
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  • 1.7. Any recent or current systemic therapy with an antibiotic or drug with potential anti-malarial activity (chloroquine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (allowable timeframe for use at the Investigator's discretion).
  • 1.8. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
  • 1.9. Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
  • 1.10. History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset, positive urine toxicology test for cocaine or amphetamines at screening or at inclusion, or positive urine toxicology test for cannabis at inclusion.
  • For female subjects: positive urine pregnancy test at screening and/or at the baseline visit.
  • Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study.
  • Known hypersensitivity to or contra-indications (including co-medication) for use of sulfadoxine-pyrimethamine, piperaquine, chloroquine, Malarone®, artemether-lumefantrine, primaquine or history of severe (allergic) reactions to mosquito bites.
  • Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
  • Being an employee or student of the department of Medical Microbiology of the Radboudumc or the department of Internal Medicine.
  • 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.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Radboud university medical center

    Nijmegen, Gelderland, 6525 GA

Other trials in Netherlands

About this study

Official title: 'Controlled Human Malaria Infection Study to Assess Gametocytaemia and Mosquito Transmissibility in Participants Challenged With Plasmodium Falciparum by Sporozoite Challenge to Establish a Model for the Evaluation of Transmission-blocking Interventions'

This is a single-center, open label study. The primary aim of this project is to develop a controlled human malaria infection transmission model ("CHMI-trans") or "challenge model" to evaluate the capacity of vaccines, biologics (monoclonal antibodies, or mAbs), and drugs to block malaria parasite transmission by assessing infectiousness of Plasmodium falciparum (Pf) gametocyte carriers for Anopheles mosquitoes.

Read the detailed description

A total of 32 volunteers will be randomly assigned to four groups (n=8) and subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes (3D7 clone). Treatment is subsequently initiated to induce gametocytaemia (treatment 1, DT1) and to clear pathogenic asexual parasites whilst leaving gametocytes unaffected (treatment 2, DT2). At the end of the study, treatment of all parasite stages is provided following national treatment guidelines (end treatment, ET).

Once malaria infections are detected by 18S qPCR positive (day of treatment 1 [DT1]), groups 1 and 2 will be treated with a course of subcurative sulfadoxine-pyrimethamine (SP) (SP low, 500mg/25mg). Groups 3 and 4 will receive piperaquine (Pip) in a low-dose (Pip low, 480 mg). After DT1, volunteers will receive a curative treatment (DT2) when a recrudescence of asexual parasitaemia occurs or on day 21 post challenge infection, whichever comes first. Volunteers in group 1 (SP low/SP high) will be treated with sulfadoxine-pyrimethamine (1000mg/50mg) and group 2 (SP low/Pip high) with piperaquine (960mg). Volunteers in group 3 (Pip low/Pip high) will be treated with piperaquine (960mg) and group 4 (Pip low/SP high) with sulfadoxine-pyrimethamine (1000mg/50mg). To ensure the radical clearance of all parasite stages, all volunteers will receive a final treatment (ET) according to national guidelines with atovaquone/proguanil (Malarone®) on day 42. Daily blood samples will allow detailed quantification of gametocytes, gametocyte sex ratio and ex vivo assessments of gametocyte fitness.

Conditions
Malaria
Being tested
Sulfadoxine-pyrimethamine (low dose), Piperaquine (low dose), Sulfadoxine-pyrimethamine (high dose), Piperaquine (high dose), malaria challenge infection, P. falciparum 3D7
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sulfadoxine-pyrimethamine (low dose)Drug

    Also called Fansidar

    • subcurative regimen (500mg/25mg)

  • Piperaquine (low dose)Drug

    Also called piperaquine phosphate

    • subcurative regimen (480 mg)

  • Sulfadoxine-pyrimethamine (high dose)Drug

    Also called Fansidar

    • curative regimen (1000mg/50mg)

  • Piperaquine (high dose)Drug

    Also called piperaquine phosphate

    • curative regimen (960 mg)

  • malaria challenge infection, P. falciparum 3D7Biological

    Also called 3D7 Plasmodium falciparum

    malaria challenge infection by P. falciparum 3D7-infected mosquito bites

  • Atovaquone-proguanilDrug

    Also called Malarone

    • curative regimen: 1000/400 mg, for 3 days
Study groups in NCT02836002
Study groupRoleWhat they receive
Group 1 - SP low/SP highExperimentalGroup 1 will be treated with a course of subcurative sulfadoxine-pyrimethamine (SP) (SP low, 500mg/25mg) as treatment 1. As treatment 2 (SP high) volunteers will receive a treatment with sulfadoxine-pyrimethamine (1000mg/50mg). Group 1 will receive a malaria challenge infection, P. falciparum 3D7 -infected mosquito bites Final treatment with a curative regimen of atovaquone/proguanil (malarone).
Receives: Drug: Sulfadoxine-pyrimethamine (low dose); Drug: Sulfadoxine-pyrimethamine (high dose); Biological: malaria challenge infection, P. falciparum 3D7; Drug: Atovaquone-proguanil
Group 2 - SP low/Pip highExperimentalGroup 2 will be treated with a course of subcurative sulfadoxine-pyrimethamine (SP) (SP low, 500mg/25mg) as treatment 1. As treatment 2 (Pip high) volunteers will receive a treatment with piperaquine (960mg). Group 2 will receive a malaria challenge infection, P. falciparum 3D7 -infected mosquito bites Final treatment with a curative regimen of atovaquone/proguanil (malarone).
Receives: Drug: Sulfadoxine-pyrimethamine (low dose); Drug: Piperaquine (high dose); Biological: malaria challenge infection, P. falciparum 3D7; Drug: Atovaquone-proguanil
Group 3 - Pip low/Pip highExperimentalGroup 3 will receive piperaquine (Pip) in a low-dose (Pip low, 480 mg) as treatment 1. As treatment 2 (Pip high) volunteers will receive a treatment with piperaquine (960mg). Group 3 will receive a malaria challenge infection, P. falciparum 3D7 -infected mosquito bites Final treatment with a curative regimen of atovaquone/proguanil (malarone).
Receives: Drug: Piperaquine (low dose); Drug: Piperaquine (high dose); Biological: malaria challenge infection, P. falciparum 3D7; Drug: Atovaquone-proguanil
Group 4 - Pip low/SP highExperimentalGroup 4 will receive piperaquine (Pip) in a low-dose (Pip low, 480 mg) as treatment 1. As treatment 2 (SP high) volunteers will receive a treatment with sulfadoxine-pyrimethamine (1000mg/50mg). Group 4 will receive a malaria challenge infection, P. falciparum 3D7 -infected mosquito bites Final treatment with a curative regimen of atovaquone/proguanil (malarone).
Receives: Drug: Piperaquine (low dose); Drug: Sulfadoxine-pyrimethamine (high dose); Biological: malaria challenge infection, P. falciparum 3D7; Drug: Atovaquone-proguanil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency and magnitude of adverse events in the CHMI-trans model in study groups

    Frequency and magnitude of adverse events in the CHMI-trans model in study groups.

    Measured: up to day 42 after challenge infection

  2. gametocyte prevalence

    Prevalence of gametocytes in the CHMI-trans model in study groups.

    Measured: up to day 42 after challenge infection

Secondary outcomes (3)

  1. peak density gametocytes

    Peak density and time-point of peak density of gametocytes by qRT-PCR.

    Measured: up to day 42 after challenge infection

  2. AUC gametocytes

    The area under the curve of gametocyte density versus time.

    Measured: up to day 42 after challenge infection

  3. Gametocyte sex-ratio

    ratio of male-female gametes

    Measured: up to day 42 after challenge infection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2016 (estimated)
  2. Study startJun 2016
  3. Primary completion29 Jun 2017
  4. Study completion29 Jun 2017

Resources

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 1/2
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02836002
Sponsor's protocol ID
CHMI-trans1
Acronym
CHMI-trans1
Status last verified
Sep 2017
First submitted
6 Jul 2016
Last updated
23 Mar 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Reuling IJ, van de Schans LA, Coffeng LE, Lanke K, Meerstein-Kessel L, Graumans W, van Gemert GJ, Teelen K, Siebelink-Stoter R, van de Vegte-Bolmer M, de Mast Q, van der Ven AJ, Ivinson K, Hermsen CC, de Vlas S, Bradley J, Collins KA, Ockenhouse CF, McCarthy J, Sauerwein RW, Bousema T. A randomized feasibility trial comparing four antimalarial drug regimens to induce Plasmodium falciparum gametocytemia in the controlled human malaria infection model. Elife. 2018 Feb 27;7:e31549. doi: 10.7554/eLife.31549.

    PubMed 29482720

  • Post A, Kabore B, Reuling IJ, Bognini J, van der Heijden W, Diallo S, Lompo P, Kam B, Herssens N, Lanke K, Bousema T, Sauerwein RW, Tinto H, Jacobs J, de Mast Q, van der Ven AJ. The XN-30 hematology analyzer for rapid sensitive detection of malaria: a diagnostic accuracy study. BMC Med. 2019 May 31;17(1):103. doi: 10.1186/s12916-019-1334-5.

    PubMed 31146732

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sulfadoxine-pyrimethamine (low dose), Piperaquine (low dose) and Sulfadoxine-pyrimethamine (high dose) in people with Malaria, run by Radboud University Medical Center at 1 site 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 12 inclusion and 16 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 23 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Frequency and magnitude of adverse events in the CHMI-trans model in study groups (time frame: up to day 42 after challenge infection). The study lists 2 primary outcomes in all. 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 NCT02836002, which also lists 2 linked publications.

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 23 Mar 2018.

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