search
Back to results

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

Primary Purpose

Malaria, Falciparum

Status
Withdrawn
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Azithromycin capsules
Placebo
Immunization with falciparum
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Malaria, Falciparum focused on measuring Malaria, P falciparum, Chloroquine, Azithromycin, Immunization

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Leiden University Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Placebo Comparator

Arm Label

CQ and falciparum immunization

CQ/AZM and falciparum immunization

CQ and AZM control

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Volunteers falciparum positive by thick smear
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
Duration of pre-patent period after challenge infection as measured by microscopy (thick smear)
Kinetics of parasitemia by PCR
Development of parasitemia as measured by PCR
Adverse events
Frequency of adverse events in study groups
Immune responses
Immune responses between study groups

Full Information

First Posted
January 31, 2013
Last Updated
November 12, 2014
Sponsor
Radboud University Medical Center
Collaborators
Leiden University Medical Center, Medicines for Malaria Venture
search

1. Study Identification

Unique Protocol Identification Number
NCT01783340
Brief Title
Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis
Acronym
MMV
Official Title
Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Withdrawn
Why Stopped
No funding
Study Start Date
April 2013 (undefined)
Primary Completion Date
December 2013 (Anticipated)
Study Completion Date
April 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
Collaborators
Leiden University Medical Center, Medicines for Malaria Venture

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria, Falciparum
Keywords
Malaria, P falciparum, Chloroquine, Azithromycin, Immunization

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CQ and falciparum immunization
Arm Type
Active Comparator
Arm Description
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.
Arm Title
CQ/AZM and falciparum immunization
Arm Type
Experimental
Arm Description
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.
Arm Title
CQ and AZM control
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Azithromycin capsules
Other Intervention Name(s)
Zithromax
Intervention Description
Azithromycin capsules will be administered at each immunization
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules will be administered at each immunization
Intervention Type
Biological
Intervention Name(s)
Immunization with falciparum
Intervention Description
three inoculations with 5 infected mosquito bites
Primary Outcome Measure Information:
Title
Volunteers falciparum positive by thick smear
Description
Percentage of P. falciparum thick smear negative volunteers on day 21 (protection against challenge infection)
Time Frame
One year
Secondary Outcome Measure Information:
Title
Duration of pre-patent period by thick smear
Description
Duration of pre-patent period after challenge infection as measured by microscopy (thick smear)
Time Frame
One year
Title
Kinetics of parasitemia by PCR
Description
Development of parasitemia as measured by PCR
Time Frame
One year
Title
Adverse events
Description
Frequency of adverse events in study groups
Time Frame
One year
Title
Immune responses
Description
Immune responses between study groups
Time Frame
One year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 and ≤ 35 years healthy volunteers (males or females) Good health based on history and clinical examination Negative pregnancy serum test For females who are sexually active: use of adequate contraception (incl. condom use) Signing of the informed consent form, thereby demonstrating understanding of the meaning and procedures of the study Agreement to inform the general practitioner and to sign a request to release medical information concerning contra-indications for participation in the study Willingness to undergo a Pf controlled infection through mosquito bites 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) Reachable (24/7) by mobile phone during the whole study period Available to attend all study visits Agreement to refrain from blood donation or for other purposes, during the whole study period Willingness to undergo HIV, hepatitis B and hepatitis C tests Negative urine toxicology screening test at screening visit and the day before challenge Willingness to take a prophylactic regime of chloroquine or chloroquine/azithromycin combination and a curative regimen of Malarone® after challenge. Exclusion Criteria: History of malaria Plans to travel to malaria endemic areas during the study period Plans to travel outside of the Netherlands during the challenge period History of stay in malaria endemic areas for more than 6 months Previous participation in any malaria vaccine study and/or positive serology for Pf 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 History of diabetes mellitus or cancer (except basal cell carcinoma of the skin) History of arrhythmias or prolonged QT-interval Positive family history in 1st and 2nd degree relatives for cardiac events < 50 years old An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system Clinically significant abnormalities in electrocardiogram (ECG) at screening Body Mass Index (BMI) below 18 or above 30 kg/m2 Any clinically significant deviation from the normal range in biochemistry or haematology blood tests or in urine analysis Positive HIV, HBV or HCV tests Participation in any other clinical study within 30 days prior to the onset of the study Enrolment in any other clinical study during the study period Pregnancy or lactation for women Volunteers unable to give written informed consent Volunteers unable to be closely followed for social, geographic or psychological reasons History of (soft) drugs or alcohol abuse interfering with normal social function A history of treatment for psychiatric disease A history of epileptic insults in the volunteer Contra-indications for use of Malarone®, chloroquine or azithromycin. This includes hypersensitivity or treatment taken by the volunteer that interferes with mentioned study drugs. 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 Any confirmed or suspected immunosuppressive or immunodeficient condition, including (functional) asplenia Co-workers or trainees of the departments of Medical Microbiology, Parasitology, or Internal Medicine of the Leiden University Medical Centre A history of sickle cell anaemia, sickle cell trait, thalassemia, thalassemia trait or G6PD deficiency
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
RW Sauerwein, MD PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
LG Visser, MD PhD
Organizational Affiliation
Leiden University Medical Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leiden University Medical Centre
City
Leiden
ZIP/Postal Code
2333ZA
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
19641203
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs