Primary objective: To determine whether CPS-immunization with NF54 Plasmodium falciparum parasites provides protection against challenge with the genetically distinct P. falciparum clones, NF135.C10 or NF166.C8.Secondary objectives:• To investigate…
ID
Source
Brief title
Condition
- Protozoal infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time to parasitemia in volunteers after malaria challenge infection.
Secondary outcome
• Antigen specificity of CPS-immunization induced antibodies for protection
against pre-erythrocytic stages of Plasmodium falciparum.
• The specificity of CPS-immunization induced T cell responses against
pre-erythrocytic stages of Plasmodium falciparum.
Background 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. 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. Controlled human malaria infections (CHMIs)
have been demonstrated to be a powerful tool in malaria vaccine research. It
has been shown previously that if healthy human volunteers taking chloroquine
chemoprophylaxis are repeatedly exposed to Plasmodium sporozoites through the
bites of infected mosquitoes, they are fully protected against a later
challenge infection with a homologous 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 parasite clones. To further consider the development of whole
sporozoite based vaccines and in order to better understand the protective
immunity induced by CPS-immunization, it is essential to investigate whether
heterologous protection against genetically diverse P. falciparum clones can be
induced.
Study objective
Primary objective:
To determine whether CPS-immunization with NF54 Plasmodium falciparum parasites
provides protection against challenge with the genetically distinct P.
falciparum clones, NF135.C10 or NF166.C8.
Secondary objectives:
• To investigate Plasmodium falciparum specific T cell responses in
CPS-immunized volunteers.
• To delineate the antibody repertoire directed against Plasmodium falciparum
in CPS-immunized volunteers.
Study design
This is a single center, randomized, double-blind study. A total of 40
volunteers will be included and divided into six groups. The first group (n=10)
will receive CPS-immunization with NF54 and a challenge infection with
NF135.C10 parasites. The second group (n=10) will receive CPS-immunization with
NF54 and a challenge infection with NF166.C8 parasites. The third group (n=5)
will receive CPS-immunization with NF54 and challenge infection with NF54
parasites. Groups 4, 5 and 6 (n=5 for each group) will receive chloroquine
prophylaxis and bites from uninfected mosquitoes during the immunization phase
and challenge infection with NF135.C10, NF166.C8 or NF54, respectively.
Intervention
A total of three CPS-immunizations will be performed with bites from 15
Plasmodium falciparum infected mosquitoes or uninfected controls per
immunization over a period of three months, during which all volunteers will
take chloroquine prophylaxis. All volunteers will undergo malaria challenge
infection by exposure to bites from up to 5 Plasmodium falciparum sporozoite
infected mosquitoes, infected with either NF135.C10, NF166.C8 or NF54
parasites.
Study burden and risks
The study is associated with several short periods of intense clinical
monitoring with frequent site visits (up to two times a day) and blood
examinations. As it is unpredictable when subjects will develop a positive qPCR
or thick blood smear, it is impossible to state the exact number of site visits
and blood examinations. However, the maximum number of site visits and blood
examinations will be 61. The maximum amount of collected blood over the period
of 8 months will be 1000 mL. Additionally, periodical physical examinations
will be performed and the subject is asked to complete a diary.
Geert Grooteplein 28
Nijmegen 6525 GA
NL
Geert Grooteplein 28
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion 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 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.
- 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.
Exclusion criteria
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, or psychiatric disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results.
- Body weight <50 kg or Body Mass Index (BMI) <18.0 or >30.0 kg/m2 at screening.
- 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.
- A history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD deficiency.
- History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
- Positive HIV, HBV or HCV screening tests.
- 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.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
- Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
- 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 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02098590 |
| CCMO | NL48732.091.14 |