Re-exposure of Human Volunteers to a Heterologous Strain of P. Falciparum Sporozoites

NCT01660854 | Completed DMC

• 1 other identifier: TIP4
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

In a previous study (NL33904.091.10) the investigators challenged 24 volunteers after Chloroquine Prophylaxis Sporozoites (CPS) immunization with 45, 30 or 15 infected mosquito-bites respectively. The availability of this immunized cohort opens the unique opportunity to determine protection to a heterologous challenge for both of the protected and unprotected volunteers as the previous challenge infection might have served as immunological boost to the unprotected volunteers. In the current observational, proof of principle study, the investigators aim to investigate the protection on an individual basis of these previously immunized and challenged volunteers against a heterologous P. falciparum challenge.

Conditions

Malaria, Falciparum

Keywords

Plasmodium; falciparum; malaria; heterologous; immunity

Outcome Measures

Primary Outcomes (1)

• Duration of prepatent period after challenge infection as measured by microscopy

  21 days after challenge

Secondary Outcomes (3)

• • Parasitemia and kinetics of parasitemia as measured by PCR

  21 days after challenge

• Frequency of signs or symptoms in study groups

  21 days after challenge

• • Immune responses between study groups

  21 days after challenge

Study Arms (2)

Heterologous challenge

EXPERIMENTAL

Biological: Heterologous challenge with 5 infected mosquito bites (NF135) after previous CPS immunization and challenge. Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone. Other Name: atovaquone/proguanil

Biological: Heterologous challenge; Drug: Malarone treatment

Challenge control

ACTIVE COMPARATOR

Biological: Plasmodium falciparum mosquito challenge by the bites of 5 Plasmodium falciparum infected mosquitoes (NF135). Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone. Other Name: atovaquone/proguanil

Biological: Heterologous challenge; Drug: Malarone treatment

Interventions

Heterologous challenge BIOLOGICAL

challenge by the bites of 5 Plasmodium falciparum infected mosquitoes.

Challenge control; Heterologous challenge

Malarone treatment DRUG

Three days: 4 tablets 250/100mg per day

Also known as: atovaquon/proguanil

Challenge control; Heterologous challenge

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 and ≤ 35 years healthy volunteers (males or females)
• Good health based on history and clinical examination
• Negative pregnancy test
• Use of adequate contraception for females
• Signing of the informed consent form, thereby demonstrating understanding of the meaning and procedures of the study
• Agreement to inform the general practitioner and to sign a request to release medical information concerning contra-indications for participation in the study
• Willingness to undergo a Pf controlled challenge through mosquito bites
• Agreement to stay in a hotel room close to the trial centre during a part of the study (Day 5 after challenge till treatment is finished)
• Reachable (24/7) by mobile phone during the whole study period
• Available to attend all study visit
• Agreement to refrain from blood donation to Sanquin or for other purposes, during the whole study period
• Willingness to undergo HIV, hepatitis B and hepatitis C tests
• Negative urine toxicology screening test at screening visit and the day before challenge
• Willingness to take a curative regimen of Malarone®

You may not qualify if:

• History of malaria (other than participation in ZonMw1 study) or residence in malaria endemic areas within the past six months
• Plans to travel to malaria endemic areas during the study period
• Plans to travel outside of the Netherlands during the challenge period
• Previous participation in any malaria vaccine study and/or positive serology for Pf (except ZonMw1 volunteers)
• Symptoms, physical signs and laboratory values suggestive of systemic disorders including 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 volunteers
• History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
• History of arrhythmias or prolonged QT-interval
• Positive family history in 1st and 2nd degree relatives for cardiac events \< 50 years old
• An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system
• Clinically significant abnormalities in electrocardiogram (ECG) at screening
• Body Mass Index (BMI) below 18 or above 30 kg/m2
• Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis
• Positive HIV, HBV or HCV tests
• Participation in any other clinical study within 30 days prior to the onset of the study
• Enrollment in any other clinical study during the study period

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Leiden University Medical Center: collaborator

Study Sites (1)

Leiden University Medical Centre

Leiden, Leiden, 2333ZA, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 19641203 BACKGROUND

• Schats R, Bijker EM, van Gemert GJ, Graumans W, van de Vegte-Bolmer M, van Lieshout L, Haks MC, Hermsen CC, Scholzen A, Visser LG, Sauerwein RW. Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites. PLoS One. 2015 May 1;10(5):e0124243. doi: 10.1371/journal.pone.0124243. eCollection 2015.

  PMID: 25933168 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

Proguanil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• RW Sauerwein, PhD

  Radboud University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: August 9, 2012
• Study Start: July 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: February 13, 2013

Record last verified: 2012-07

Locations

NL (1)