Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis

Condition(s) targeted: Malaria, Falciparum

Intervention: Azithromycin capsules (Drug); Placebo (Drug); Immunization with falciparum (Biological)

Phase: Phase 1/Phase 2

Status: Withdrawn

Sponsored by: Radboud University

Official(s) and/or principal investigator(s):
RW Sauerwein, MD PhD, Study Director, Affiliation: Radboud University
LG Visser, MD PhD, Principal Investigator, Affiliation: Leiden University Medical Centre

This study will assess the superior protective immunity of the combination of chloroquine and azithromycin prophylaxis under Chemoprophylaxis Sporozoites (CPS) immunization versus a standard chloroquine prophylactic regimen.

Official title: Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: Volunteers falciparum positive by thick smear

Secondary outcome:

Duration of pre-patent period by thick smear

Kinetics of parasitemia by PCR

Adverse events

Immune responses

Detailed description: This study assesses the superiority of protective immunity of the combination of chloroquine and azithromycin prophylaxis under Chemoprophylaxis Sporozoites (CPS) immunization versus a standard chloroquine prophylactic regimen.

Minimum age: 18 Years. Maximum age: 35 Years. Gender(s): Both.

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 serum test 4. For females who are sexually active: use of adequate contraception (incl. condom use) 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 infection through mosquito bites 8. Agreement to stay in a hotel room close to the trial centre during a part of the study (Day 7 till day 15 after challenge) 9. Reachable (24/7) by mobile phone during the whole study period 10. Available to attend all study visits 11. Agreement to refrain from blood donation 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 prophylactic regime of chloroquine or chloroquine/azithromycin combination and a curative regimen of Malarone® after challenge. Exclusion Criteria: 1. History of malaria 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. History of stay in malaria endemic areas for more than 6 months 5. Previous participation in any malaria vaccine study and/or positive serology for Pf 6. 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 volunteer 7. History of diabetes mellitus or cancer (except basal cell carcinoma of the skin) 8. History of arrhythmias or prolonged QT-interval 9. Positive family history in 1st and 2nd degree relatives for cardiac events < 50 years old 10. An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system 11. Clinically significant abnormalities in electrocardiogram (ECG) at screening 12. Body Mass Index (BMI) below 18 or above 30 kg/m2 13. Any clinically significant deviation from the normal range in biochemistry or haematology blood tests or in urine analysis 14. Positive HIV, HBV or HCV tests 15. Participation in any other clinical study within 30 days prior to the onset of the study 16. Enrolment in any other clinical study during the study period 17. Pregnancy or lactation for women 18. Volunteers unable to give written informed consent 19. Volunteers unable to be closely followed for social, geographic or psychological reasons 20. History of (soft) drugs or alcohol abuse interfering with normal social function 21. A history of treatment for psychiatric disease 22. A history of epileptic insults in the volunteer 23. Contra-indications for use of Malarone®, chloroquine or azithromycin. This includes hypersensitivity or treatment taken by the volunteer that interferes with mentioned study drugs. 24. The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (topical corticosteroids and oral anti-histaminic are allowed) and during the study period 25. Any confirmed or suspected immunosuppressive or immunodeficient condition, including (functional) asplenia 26. Co-workers or trainees of the departments of Medical Microbiology, Parasitology, or Internal Medicine of the Leiden University Medical Centre 27. A history of sickle cell anaemia, sickle cell trait, thalassemia, thalassemia trait or G6PD deficiency

Leiden University Medical Centre, Leiden 2333ZA, Netherlands

Starting date: April 2013
Last updated: November 12, 2014