Clinical trial NCT01783340: Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis
Official title: Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Malaria, Falciparum
Keywords: Malaria
P falciparum
Chloroquine
Azithromycin
Immunization
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
name: Medicines for Malaria Venture
First posted: 2013-02-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

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.

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 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

Primary outcomes:
measure: Volunteers falciparum positive by thick smear
timeFrame: One year
Secondary outcomes:
measure: Duration of pre-patent period by thick smear
timeFrame: One year
measure: Kinetics of parasitemia by PCR
timeFrame: One year
measure: Adverse events
timeFrame: One year
measure: Immune responses
timeFrame: One year
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
Study officials:
affiliation: Radboud University Medical Center
name: RW Sauerwein, MD PhD
role: STUDY_DIRECTOR
affiliation: Leiden University Medical Centre
name: LG Visser, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.