Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis (MMV)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2012 by Radboud University
Sponsor:
Collaborators:
Leiden University Medical Center
Medicines for Malaria Venture
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01783340
First received: January 31, 2013
Last updated: NA
Last verified: November 2012
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Malaria, Falciparum
Chloroquine
Azithromycin
Immunization
Drug: Azithromycin capsules
Drug: Placebo
Biological: Immunization with falciparum
Drug: Atovaquone/Proguanil
Biological: Challenge with falciparum
Phase 1
Phase 2

Study Type: Interventional
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
Official Title: Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Volunteers falciparum positive by thick smear [ Time Frame: One year ] [ Designated as safety issue: No ]
    Percentage of P. falciparum thick smear negative volunteers on day 21 (protection against challenge infection)


Secondary Outcome Measures:
  • Duration of pre-patent period by thick smear [ Time Frame: One year ] [ Designated as safety issue: No ]
    Duration of pre-patent period after challenge infection as measured by microscopy (thick smear)

  • Kinetics of parasitemia by PCR [ Time Frame: One year ] [ Designated as safety issue: No ]
    Development of parasitemia as measured by PCR

  • Adverse events [ Time Frame: One year ] [ Designated as safety issue: Yes ]
    Frequency of adverse events in study groups

  • Immune responses [ Time Frame: One year ] [ Designated as safety issue: No ]
    Immune responses between study groups


Estimated Enrollment: 25
Study Start Date: April 2013
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chloroquine and falciparum immunization

This arm will receive chloroquine prophylaxis, a placebo during immunizations and three times 5 infected mosquito-bites (immunizations). Standard Chloroquine prophylactic regime: a loading dose of 300 mg on day 1 and day 3 and then 300 mg once a week, starting on day 7, for a total duration of 13 weeks.

Placebo capsules daily on three consecutive days starting on each of three immunization days.

Challenge: Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.

When thick smear positive, of at day 21 after challenge, a standard 3 day treatment of Malarone will be given.

Drug: Placebo
Other Name: Placebo
Biological: Immunization with falciparum Drug: Atovaquone/Proguanil
Other Name: Malarone
Biological: Challenge with falciparum
Experimental: Chloroquine/Azithromycin and falciparum immunization

This arm will receive chloroquine and azithromycin prophylaxis and three times 5 infected mosquito-bites (immunizations).

Standard Chloroquine prophylactic regime: a loading dose of 300 mg on day 1 and day 3 and then 300 mg once a week, starting on day 7, for a total duration of 13 weeks.

Azithromycin capsules 1000mg daily on three consecutive days starting on each of three immunization days.

Challenge: Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.

When thick smear positive, of at day 21 after challenge, a standard 3 day treatment of Malarone will be given.

Drug: Azithromycin capsules
Other Name: Zithromax
Biological: Immunization with falciparum Drug: Atovaquone/Proguanil
Other Name: Malarone
Biological: Challenge with falciparum
Placebo Comparator: Chloroquine and Azithromycin control

This arm will receive chloroquine and azithromycin prophylaxis and three times 5 uninfected mosquito-bites during immunization. Standard Chloroquine prophylactic regime: a loading dose of 300 mg on day 1 and day 3 and then 300 mg once a week, starting on day 7, for a total duration of 13 weeks.

Azithromycin capsules 1000mg daily on three consecutive days starting on each of three immunization days.

Challenge: Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.

When thick smear positive, of at day 21 after challenge, a standard 3 day treatment of Malarone will be given.

Drug: Azithromycin capsules
Other Name: Zithromax
Drug: Atovaquone/Proguanil
Other Name: Malarone
Biological: Challenge with falciparum

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01783340

Contacts
Contact: Remko Schats, MD 0031715262620 r.schats@lumc.nl
Contact: Leo Visser, MD, PhD 0031715262620 l.g.visser@lumc.nl

Locations
Netherlands
Leiden University Medical Centre Not yet recruiting
Leiden, Netherlands, 2333ZA
Contact: Remko Schats, MD    0031715262620    r.schats@lumc.nl   
Contact: Leo Visser, MD PhD    0031715262620    l.g.visser@lumc.nl   
Sub-Investigator: Remko Schats, MD         
Principal Investigator: Leo Visser, MD PhD         
Sub-Investigator: Maurits van Meer, MD PhD         
Sponsors and Collaborators
Radboud University
Leiden University Medical Center
Medicines for Malaria Venture
Investigators
Study Director: RW Sauerwein, MD PhD Radboud University
Principal Investigator: LG Visser, MD PhD Leiden University Medical Centre
  More Information

Publications:
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01783340     History of Changes
Other Study ID Numbers: MMV, NL42517.000.12
Study First Received: January 31, 2013
Last Updated: January 31, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Malaria
P falciparum
Chloroquine
Azithromycin
Immunization

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Chloroquine
Chloroquine diphosphate
Proguanil
Atovaquone
Malarone
Azithromycin
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics
Central Nervous System Agents
Antimetabolites

ClinicalTrials.gov processed this record on July 24, 2014