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

Malaria, Falciparum Clinical Trial

— MMV  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01783340
• Other study ID #: MMV
• Secondary ID: NL42517.000.12
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: January 31, 2013
• Last updated: November 12, 2014
• Start date: April 2013
• Est. completion date: April 2014

Study information

• Verified date: November 2014
• 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

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2014
• Est. primary completion date: December 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 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

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

Related Conditions & MeSH terms

• Malaria, Falciparum

Intervention

Drug:
• Azithromycin capsules
Azithromycin capsules will be administered at each immunization
• Placebo
Placebo capsules will be administered at each immunization

Biological:
• Immunization with falciparum
three inoculations with 5 infected mosquito bites

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Centre	Leiden

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University	Leiden University Medical Center, Medicines for Malaria Venture

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 chall — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Volunteers falciparum positive by thick smear	Percentage of P. falciparum thick smear negative volunteers on day 21 (protection against challenge infection)	One year	No
Secondary	Duration of pre-patent period by thick smear	Duration of pre-patent period after challenge infection as measured by microscopy (thick smear)	One year	No
Secondary	Kinetics of parasitemia by PCR	Development of parasitemia as measured by PCR	One year	No
Secondary	Adverse events	Frequency of adverse events in study groups	One year	Yes
Secondary	Immune responses	Immune responses between study groups	One year	No