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AzTrials

MalariaBMGF2bNCT02098590

Chemoprophylaxis and Plasmodium Falciparum NF54 Sporozoite Immunization Challenged by Heterologous Infection

A study testing CPS-immunization, malaria challenge infection, P. falciparum NF135.C10 and malaria challenge infection, P. falciparum NF166.C8 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
Search all trials

Trial summary

Malaria, a disease caused by the parasite Plasmodium, is one of the world's major infectious diseases. With approximately 627.000 deaths a year, it is both a chief cause of morbidity and mortality as well as a significant contribution to ongoing poverty in endemic countries. 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?
CPS-immunization, malaria challenge infection, P. falciparum NF135.C10 and malaria challenge infection, P. falciparum NF166.C8
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteNetherlands
Study dates
Oct 2014to Nov 2015
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

  • 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 agrees to abide strictly thereby.
  • 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 5 post-infection until three days post-treatment). Furthermore the subject will remain within the Netherlands during the challenge period, not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period.
  • Subject agrees to inform his/her general practitioner about participation in the study and to sign a request to release by the General Practitioner (GP) any relevant medical information concerning possible contra-indications for participation in the study.
  • 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.
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  • For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
  • Subject has signed informed consent.
  • Subject agrees to refrain from intensive physical exercise (disproportionate to the subjects usual daily activity or exercise routine) for ten days following each immunization and during the malaria challenge period.

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) <18.0 or >30.0 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.
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  • 1.5 Positive Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (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, positive urine toxicology test for cocaine or amphetamines at screening or prior to infection or positive urine toxicology test for cannabis at inclusion or prior to infection.
  • For female subjects: positive urine pregnancy test at screening or prior to infection.
  • 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 chloroquine, Malarone or artemether-lumefantrine, or history of severe (allergic) reactions to mosquito bites.
  • 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.
  • 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

Malaria, a disease caused by the parasite Plasmodium, is one of the world's major infectious diseases. With approximately 627.000 deaths a year, it is both a chief cause of morbidity and mortality as well as a significant contribution to ongoing poverty in endemic countries. Ultimately, the key to malaria control, and hopefully eradication, would be an effective vaccine. Though a number of vaccine-candidates have entered the pipeline of pre-clinical and clinical development, they have yet to achieve the level of efficacy necessary for effective malaria prevention. It has been shown previously that if healthy human volunteers taking chloroquine chemoprophylaxis are repeatedly exposed to Plasmodium parasites through the bites of infected mosquitoes, they are fully protected against a later challenge infection with a 'homologous' (genetically similar) Plasmodium parasite. This process is known as ChemoProphylaxis and Sporozoites, or CPS-immunization. One of the obstacles to developing an effective vaccine is the genetic heterogeneity of malaria parasites. To further consider the development of whole-parasite based vaccines against malaria and in order to better understand the protective immunity induced by CPS-immunization, it is essential to investigate whether heterologous protection against genetically diverse (heterologous) P. falciparum clones can be induced.

This is a single center, randomized, double-blind study to determine whether healthy volunteers immunized with P. falciparum NF54 parasites under chloroquine prophylaxis are protected against a challenge infection with the genetically distinct NF135.C10 or NF166.C8 P. falciparum clones.

Conditions
Malaria
Being tested
CPS-immunization, malaria challenge infection, P. falciparum NF135.C10, malaria challenge infection, P. falciparum NF166.C8, malaria challenge infection, P. falciparum NF54, atovaquone/proguanil
Keywords
Malaria, Plasmodium falciparum
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.

  • CPS-immunizationBiological

    Also called chloroquin, Plasmodium falciparum NF54 sporozoites

    Subjects will be exposed 3 times to bites from 15 NF54 Plasmodium infected mosquitoes during each immunization, while taking chloroquin prophylaxis.

  • malaria challenge infection, P. falciparum NF135.C10Biological

    Also called Plasmodium falciparum NF135.C10 sporozoites

    Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites.

  • malaria challenge infection, P. falciparum NF166.C8Biological

    Also called Plasmodium falciparum NF166.C8 sporozoites

    Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF166.C8 sporozoites.

  • malaria challenge infection, P. falciparum NF54Biological

    Also called Plasmodium falciparum NF54 sporozoites

    Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites.

  • atovaquone/proguanilDrug

    Also called Malarone

    All participants will be treated with atovaquone/proguanil when they develop a malaria infection or on day 28 after malaria challenge infection.

Study groups in NCT02098590
Study groupRoleWhat they receive
NF54 CPS-immunization challenged by NF135.C10ExperimentalSubjects will receive CPS-immunization by bites from 3 x 15 NF54 P. falciparum infected mosquitoes under chloroquine prophylaxis. After stopping chloroquine subjects will receive a heterologous malaria challenge infection by exposure to the bites of 5 NF135.C10 P. falciparum infected mosquitoes. Subjects will be treated with Malarone if they develop a malaria infection or on day 28 after challenge infection.
Receives: Biological: CPS-immunization; Biological: malaria challenge infection, P. falciparum NF135.C10; Drug: atovaquone/proguanil
NF54 CPS-immunization challenged by NF166.C8ExperimentalSubjects will receive CPS-immunization by bites from 3 x 15 NF54 P. falciparum infected mosquitoes under chloroquine prophylaxis. After stopping chloroquine subjects will receive a heterologous malaria challenge infection by exposure to the bites of 5 NF166.C8 P. falciparum infected mosquitoes. Subjects will be treated with Malarone if they develop a malaria infection or on day 28 after challenge infection.
Receives: Biological: CPS-immunization; Biological: malaria challenge infection, P. falciparum NF166.C8; Drug: atovaquone/proguanil
NF54 CPS-immunization challenged by NF54Other[Negative control group, to assess effectiveness of CPS-immunization.] Subjects will receive CPS-immunization by bites from 3 x 15 NF54 P. falciparum infected mosquitoes under chloroquine prophylaxis. After stopping chloroquine subjects will receive a homologous malaria challenge infection by exposure to the bites of 5 NF54 P. falciparum infected mosquitoes. Subjects will be treated with Malarone if they develop a malaria infection or on day 28 after challenge infection.
Receives: Biological: CPS-immunization; Biological: malaria challenge infection, P. falciparum NF54; Drug: atovaquone/proguanil
Control group challenged by NF135.C10Other[Control group] Subjects will receive bites from 3 x 15 uninfected mosquitoes under chloroquine prophylaxis. After stopping chloroquine subjects will receive a malaria challenge infection by exposure to the bites of NF135.C10 P. falciparum infected mosquitoes. Subjects will be treated with Malarone if they develop a malaria infection or on day 28 after challenge infection.
Receives: Biological: malaria challenge infection, P. falciparum NF135.C10; Drug: atovaquone/proguanil
Control group challenged by NF166.C8Other[Control group] Subjects will receive bites from 3 x 15 uninfected mosquitoes under chloroquine prophylaxis. After stopping chloroquine subjects will receive a malaria challenge infection by exposure to the bites of NF166.C8 P. falciparum infected mosquitoes. Subjects will be treated with Malarone if they develop a malaria infection or on day 28 after challenge infection.
Receives: Biological: malaria challenge infection, P. falciparum NF166.C8; Drug: atovaquone/proguanil
Control group challenged by NF54Other[Control group] Subjects will receive bites from 3 x 15 uninfected mosquitoes under chloroquine prophylaxis. After stopping chloroquine subjects will receive a malaria challenge infection by exposure to the bites of NF54 P. falciparum infected mosquitoes. Subjects will be treated with Malarone if they develop a malaria infection or on day 28 after challenge infection.
Receives: Biological: malaria challenge infection, P. falciparum NF54; Drug: atovaquone/proguanil

What is being measured

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

  1. Parasitemia

    The effectiveness of CPS-immunization with NF54 sporozoites to protect against malaria challenge infection with heterologous NF135.C10 or NF166.C8 sporozoites will be determined by the time to parasitemia in immunized versus non-immunized volunteers after the challenge infection.

    Measured: day 1 - 28 after malaria challenge infection

Secondary outcomes (2)

  1. Antigen specificity of CPS-immunization induced antibodies against P. falciparum

    Blood will be drawn to isolate plasmablast for further delineation of the antibody responses following CPS-immunization.

    Measured: 6-10 days after challenge infection

  2. Specificity of CPS-immunization induced T-cell responses against P. falciparum

    Blood will be drawn to isolate monocytes and T cells, which will be used to determine the activity of T cells against specific target antigens of the pre-erythrocytic stages of Plasmodium falciparum.

    Measured: 14 days after each CPS-immunization

Timeline

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

  1. First posted28 Mar 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionNov 2015
  4. Study completionNov 2015

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 N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02098590
Sponsor's protocol ID
BMGF2b
Acronym
BMGF2b
Status last verified
Feb 2016
First submitted
25 Mar 2014
Last updated
23 Feb 2016
Results posted
No
Data monitoring committee
No

Publications

  • Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.

    PubMed 19641203

  • Roestenberg M, O'Hara GA, Duncan CJ, Epstein JE, Edwards NJ, Scholzen A, van der Ven AJ, Hermsen CC, Hill AV, Sauerwein RW. Comparison of clinical and parasitological data from controlled human malaria infection trials. PLoS One. 2012;7(6):e38434. doi: 10.1371/journal.pone.0038434. Epub 2012 Jun 11.

    PubMed 22701640

  • Walk J, Reuling IJ, Behet MC, Meerstein-Kessel L, Graumans W, van Gemert GJ, Siebelink-Stoter R, van de Vegte-Bolmer M, Janssen T, Teelen K, de Wilt JHW, de Mast Q, van der Ven AJ, Diez Benavente E, Campino S, Clark TG, Huynen MA, Hermsen CC, Bijker EM, Scholzen A, Sauerwein RW. Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial. BMC Med. 2017 Sep 13;15(1):168. doi: 10.1186/s12916-017-0923-4.

    PubMed 28903777

Questions about this trial

What is this clinical trial studying?

A study testing CPS-immunization, malaria challenge infection, P. falciparum NF135.C10 and malaria challenge infection, P. falciparum NF166.C8 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 9 inclusion and 18 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 Feb 2016. 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.

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?

Parasitemia (time frame: day 1 - 28 after malaria challenge infection). 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 NCT02098590, which also lists 3 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 Feb 2016.

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