Malaria, FalciparumPhase 1/2MMVNCT01783340
Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis
A Phase 1/2 study testing Azithromycin capsules and Immunization with falciparum in people with Malaria, Falciparum, run by Radboud University Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Falciparum
- What is being tested?
- Azithromycin capsules and Immunization with falciparum
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2013to Apr 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Malaria, Falciparum
- Being tested
- Azithromycin capsules, Placebo, Immunization with falciparum
- Keywords
- Malaria, P falciparum, Chloroquine, Azithromycin, Immunization
- Medical subject headings
- Malaria, Falciparum, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin capsulesDrug
Also called Zithromax
Azithromycin capsules will be administered at each immunization
PlaceboDrug
Placebo capsules will be administered at each immunization
Immunization with falciparumBiological
three inoculations with 5 infected mosquito bites
| Study group | Role | What they receive |
|---|---|---|
| CQ and falciparum immunization | Active comparator | 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. Receives: Drug: Placebo; Biological: Immunization with falciparum |
| CQ/AZM and falciparum immunization | Experimental | 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. Receives: Drug: Azithromycin capsules; Biological: Immunization with falciparum |
| CQ and AZM control | Placebo comparator | 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. Receives: Drug: Azithromycin capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volunteers falciparum positive by thick smear
Percentage of P. falciparum thick smear negative volunteers on day 21 (protection against challenge infection)
Measured: One year
Secondary outcomes (4)
Duration of pre-patent period by thick smear
Duration of pre-patent period after challenge infection as measured by microscopy (thick smear)
Measured: One year
Kinetics of parasitemia by PCR
Development of parasitemia as measured by PCR
Measured: One year
Adverse events
Frequency of adverse events in study groups
Measured: One year
Immune responses
Immune responses between study groups
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2013 (estimated)
- Study startApr 2013
- Primary completionDec 2013 (estimated)
- Study completionApr 2014 (estimated)
Why it stopped: No funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malaria, FalciparumStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center, Medicines for Malaria Venture
- Responsible party
- Sponsor
- Investigators
- RW Sauerwein, MD PhD, Study director, Radboud University Medical CenterLG Visser, MD PhD, Principal investigator, Leiden University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01783340
- Sponsor's protocol ID
- MMV
- Other IDs
- NL42517.000.12
- Acronym
- MMV
- Status last verified
- Nov 2014
- First submitted
- 31 Jan 2013
- Last updated
- 13 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19641203
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis
- ClinicalTrials.gov ID
- NCT01783340
- Acronym / sponsor ID
- MMV / MMV
- Conditions
- Malaria, Falciparum
- Keywords
- Malaria, P falciparum, Chloroquine, Azithromycin, Immunization
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Leiden University Medical Center, Medicines for Malaria Venture
- Study start
- Apr 2013
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Apr 2014 (estimated)
- First posted
- 4 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CQ and falciparum immunization | Active comparator | Drug: Placebo, Biological: Immunization with falciparumThis 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. |
| CQ/AZM and falciparum immunization | Experimental | Drug: Azithromycin capsules, Biological: Immunization with falciparumThis 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. |
| CQ and AZM control | Placebo comparator | Drug: Azithromycin capsulesThis 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycin capsulesAlso: ZithromaxAzithromycin capsules will be administered at each immunization | Drug | CQ and AZM control, CQ/AZM and falciparum immunization |
| PlaceboPlacebo capsules will be administered at each immunization | Drug | CQ and falciparum immunization |
| Immunization with falciparumthree inoculations with 5 infected mosquito bites | Biological | CQ and falciparum immunization, CQ/AZM and falciparum immunization |
Primary outcome
Volunteers falciparum positive by thick smear
Time frame: One year
Percentage of P. falciparum thick smear negative volunteers on day 21 (protection against challenge infection)
4 secondary outcomes
Duration of pre-patent period by thick smear
Time frame: One year
Kinetics of parasitemia by PCR
Time frame: One year
Adverse events
Time frame: One year
Immune responses
Time frame: One year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2014.
- Results publication: PubMed 19641203Roestenberg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
RW Sauerwein, MD PhD study director
Radboud University Medical Center
LG Visser, MD PhD principal investigator
Leiden University Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Azithromycin capsules and Immunization with falciparum in people with Malaria, Falciparum, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volunteers falciparum positive by thick smear (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01783340, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2014.