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

Malaria, Falciparum Clinical Trial

— TIP4  

Official title:

Re-exposure of Previously Immunized and Challenged Human Volunteers to a Heterologous Strain of P. Falciparum Sporozoites

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01660854
• Other study ID #: TIP4
• Status: Completed
• Phase: N/A
• First received: July 23, 2012
• Last updated: February 12, 2013
• Start date: July 2012
• Est. completion date: January 2013

Study information

• Verified date: July 2012
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Malaria, Falciparum

Intervention

Biological:
• Heterologous challenge
challenge by the bites of 5 Plasmodium falciparum infected mosquitoes.

Drug:
• Malarone treatment
Three days: 4 tablets 250/100mg per day

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Centre	Leiden

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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, Rénia 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of prepatent period after challenge infection as measured by microscopy		21 days after challenge	No
Secondary	• Parasitemia and kinetics of parasitemia as measured by PCR		21 days after challenge	No
Secondary	Frequency of signs or symptoms in study groups		21 days after challenge	No
Secondary	• Immune responses between study groups		21 days after challenge	No