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

NCT ID: NCT01660854

Last Updated: 2013-02-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2013-01-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Heterologous challenge

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

Group Type: EXPERIMENTAL

Heterologous challenge

Intervention Type: BIOLOGICAL

challenge by the bites of 5 Plasmodium falciparum infected mosquitoes.

Malarone treatment

Intervention Type: DRUG

Three days: 4 tablets 250/100mg per day

Challenge control

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

Group Type: ACTIVE_COMPARATOR

Heterologous challenge

Intervention Type: BIOLOGICAL

challenge by the bites of 5 Plasmodium falciparum infected mosquitoes.

Malarone treatment

Intervention Type: DRUG

Three days: 4 tablets 250/100mg per day

Interventions

Heterologous challenge

challenge by the bites of 5 Plasmodium falciparum infected mosquitoes.

Intervention Type: BIOLOGICAL

Malarone treatment

Three days: 4 tablets 250/100mg per day

Intervention Type: DRUG

Other Intervention Names

atovaquon/proguanil

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 and ≤ 35 years healthy volunteers (males or females)

2. Good health based on history and clinical examination

3. Negative pregnancy test

4. Use of adequate contraception for females

5. Signing of the informed consent form, thereby demonstrating understanding of the meaning and procedures of the study

6. Agreement to inform the general practitioner and to sign a request to release medical information concerning contra-indications for participation in the study

7. Willingness to undergo a Pf controlled challenge through mosquito bites

8. 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)

9. Reachable (24/7) by mobile phone during the whole study period

10. Available to attend all study visit

11. Agreement to refrain from blood donation to Sanquin or for other purposes, during the whole study period

12. Willingness to undergo HIV, hepatitis B and hepatitis C tests

13. Negative urine toxicology screening test at screening visit and the day before challenge

14. Willingness to take a curative regimen of Malarone®

Exclusion Criteria

1. History of malaria (other than participation in ZonMw1 study) or residence in malaria endemic areas within the past six months

2. Plans to travel to malaria endemic areas during the study period

3. Plans to travel outside of the Netherlands during the challenge period

4. Previous participation in any malaria vaccine study and/or positive serology for Pf (except ZonMw1 volunteers)

5. 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

6. History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)

7. History of arrhythmias or prolonged QT-interval

8. Positive family history in 1st and 2nd degree relatives for cardiac events < 50 years old

9. An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system

10. Clinically significant abnormalities in electrocardiogram (ECG) at screening

11. Body Mass Index (BMI) below 18 or above 30 kg/m2

12. Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis

13. Positive HIV, HBV or HCV tests

14. Participation in any other clinical study within 30 days prior to the onset of the study

15. Enrollment in any other clinical study during the study period

16. For women: being pregnant or lactating

17. Volunteers unable to give written informed consent

18. Volunteers unable to be closely followed for social, geographic or psychological reasons

19. History of drug or alcohol abuse interfering with normal social function

20. A history of treatment for psychiatric disease

21. A history of convulsions

22. Contra-indications to Malarone®, including hypersensitivity or treatment taken by the volunteer that interferes with Malarone®

23. The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids and oral anti-histaminic are allowed) and during the study period

24. Any confirmed or suspected immunosuppressive or immunodeficient condition, including (functional) asplenia

25. Co-workers or trainees of the departments Infectious Diseases, Medical Microbiology or Parasitology of the Leiden University Medical Centre (LUMC) or Medical Microbiology, Parasitology, Radboud University Nijmegen (RUNMC)

26. A history of sickle cell anaemia, sickle cell trait, thalassaemia (or trait), G6PD deficiency

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

RW Sauerwein, PhD

Role: STUDY_DIRECTOR

Radboud University Medical Center

Locations

Leiden University Medical Centre

Leiden, Leiden, Netherlands

Countries

Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 19641203 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25933168 (View on PubMed)

Other Identifiers

TIP4

Identifier Type: -

Identifier Source: org_study_id