Controlled Human Malaria Infection After Bites From Mosquitoes Infected With Two Novel P. Falciparum Strains

NCT02149550 | Completed DMC

• 1 other identifier: BMGF2a
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

Conditions

Malaria

Keywords

Plasmodium falciparum; malaria

Outcome Measures

Primary Outcomes (1)

• 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.

  between day 5 and day 13

Secondary Outcomes (3)

• Time to patent parasitaemia in each group as assessed by QRT-PCR

  between day 5 and day 13

• Magnitude of first peak of parasitaemia in each group as assessed by QRT-PCR

  between day 5 and day 13

• Frequency of malaria-related symptoms and signs in each group

  between day 0 and day 35

Study Arms (6)

NF135 n=5

ACTIVE COMPARATOR

Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes

Other: NF135 n=5

NF135 n=2

EXPERIMENTAL

Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes

Other: NF135 n=2

NF135 n=1

EXPERIMENTAL

Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito

Other: NF135 n=1

NF166 n=5

ACTIVE COMPARATOR

Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes

Other: NF166 n=5

NF166 n=2

EXPERIMENTAL

Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes

Other: NF166 n=2

NF166 n=1

EXPERIMENTAL

Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito

Other: NF166 n=1

Interventions

NF135 n=5 OTHER

Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

NF135 n=5

NF135 n=2 OTHER

Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes.

NF135 n=2

NF135 n=1 OTHER

Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito.

NF135 n=1

NF166 n=5 OTHER

Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.

NF166 n=5

NF166 n=2 OTHER

Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes.

NF166 n=2

NF166 n=1 OTHER

Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito.

NF166 n=1

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 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.
• 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.
• 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.

You may not qualify if:

• 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:
• 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.
• 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. 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.
• 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.
• 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.
• 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 atovaquone-proguanil (Malarone®) or artemether-lumefantrine (Riamet®), 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, the department of Internal Medicine or Laboratory of the Havenziekenhuis or the department of Medical Microbiology \& Infectious Diseases of the Erasmus MC.
• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Havenziekenhuis: collaborator

Study Sites (2)

UMC St Radboud

Nijmegen, Netherlands

Location

Havenziekenhuis

Rotterdam, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 28637923 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Perry van Genderen, MD, PhD

  Havenziekenhuis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2014
• First Posted: May 29, 2014
• Study Start: August 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 24, 2014

Record last verified: 2014-11

Locations

NL (2)