MalariaPhase 2BCG-EHMINCT02692963
Safety and Protective Efficacy of BCG Vaccination Against Controlled Human Malaria Infection
A Phase 2 study testing BCG vaccination in people with Malaria and Plasmodium Falciparum, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
The Bacillus Calmette-Guérin (BCG) vaccine, a live attenuated Mycobacterium bovis vaccine, has been used to prevent tuberculosis for almost a century, and it is still the most used vaccine in the world. There is also circumstantial and indirect evidence that BCG vaccination can protect against malaria. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Plasmodium Falciparum
- What is being tested?
- BCG vaccination
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2016to Feb 2017
- Phase
- Phase 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
- Subject is aged ≥18 and ≤35 years and in good health.
- Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
- Subject is able to communicate well with the investigator and is available to attend all study visits.
- The subject will remain within the Netherlands during the challenge period, not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period.
- Subject agrees to inform his/her general practitioner about participation in the study and to sign a request to release by the General Practitioner (GP), and medical specialist when necessary, any relevant medical information concerning possible contra-indications for participation in the study.
- The subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period and for a defined period thereafter according to current Sanquin guidelines.
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- For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
- Subject agrees to refrain from intensive physical exercise (disproportionate to the subjects usual daily activity or exercise routine) during the malaria challenge period.
- Subject has signed informed consent.
Who cannot join
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following.
- 1.1 Body weight <50 kg or Body Mass lndex (BM l) <18 or >30 kg/m2 at screening. 1.2 A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of >5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.
- 1.3 A medical history of functional asplenia, sickle cell trait disease, thalassaemia trait/disease or G6PD deficiency.
- 1.4 History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
- 1.5 Screening tests positive for Human immunodeficiency Virus (HlV), or active Hepatitis B Virus (HBS) or Hepatitis C Virus (HCV).
- 1.6 Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period.
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- 1.7 Use of Non-steroidal Anti-inflammatory Drugs (NSAlDs) in the four weeks prior to study start or expected use of NSAIDS during the study period.
- 1.8 History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
- 1.9 Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
- 1.10 History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset, positive urine toxicology test for cocaine or amphetamines at screening or prior to infection, or positive urine toxicology test for cannabis at inclusion.
- For female subjects: positive urine pregnancy test at screening or at inclusion.
- Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study.
- Known hypersensitivity to or contra-indications (including co-medication) for use of chloroquine, Malarone or artemether-lumefantrine, or history of severe (allergic) reactions to mosquito bites.
- Receipt of any vaccinations in the 3 months prior to the start of the study or plans to receive any other vaccinations during the study period or up to 90 days thereafter.
- Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
- Being an employee or student of the department of Medical Microbiology of the Radboudumc or the department of lnternal Medicine.
- Previous BCG-vaccination; history of tuberculosis or positive Mantoux test; or positive whole blood interferon-gamma (IFN-γ) response to restimulation with M. tuberculosis at screening.
- Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
The Bacillus Calmette-Guérin (BCG) vaccine, a live attenuated Mycobacterium bovis vaccine, has been used to prevent tuberculosis for almost a century, and it is still the most used vaccine in the world. There is also circumstantial and indirect evidence that BCG vaccination can protect against malaria. Investigators hypothesize that BCG vaccination can offer protection against malaria in the Controlled Human Malaria Infection (CHMI) model.
A total of 20 healthy male and female volunteers will participate in this randomized, single-blind clinical trial. Volunteers will be randomized to receive either BCG vaccination (BCG vaccine SSI) (group 1, n=10) or no treatment (group 2, n=10). Five weeks after vaccination of group 1 volunteers, all volunteers will undergo a CHMI administered by the bites of five P. falciparum infected Anopheles mosquitoes.
- Conditions
- Malaria, Plasmodium Falciparum
- Being tested
- BCG vaccination
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG vaccinationBiological
BCG vaccine InterVax
| Study group | Role | What they receive |
|---|---|---|
| BCG vaccination | Experimental | Not described Receives: Biological: BCG vaccination |
| Control | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and magnitude of adverse events
Adverse event collection and routine safety and hematology laboratory evaluations will be conducted from the day of BCG vaccination until day 37 after CHMI.
Measured: day of BCG vaccination until day 37 after malaria challenge infection
Time to blood stage parasitemia detectable by qPCR
The effectiveness of BCG vaccination to protect against CHMI will be evaluated by quantitative PCR.
Measured: day 1 - 21 after malaria challenge infection
Secondary outcomes (2)
Changes in cellular (innate and adaptive) immune responses
Measured: inclusion until day 120 after malaria challenge infection
Changes in plasma cytokine levels
Measured: inclusion until day 120 after malaria challenge infection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2016 (estimated)
- Study startApr 2016
- Primary completionOct 2016
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert Sauerwein, Prof., Principal investigator, Radboud University Medical CenterMihai Netea, Prof., Principal investigator, Radboud University Medical CenterJona Walk, MD, Study director, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02692963
- Sponsor's protocol ID
- BCG-EHMI
- Other IDs
- 2015-005735-40, NL56222.091.15, 2015
- Acronym
- BCG-EHMI
- Status last verified
- Aug 2016
- First submitted
- 2 Feb 2016
- Last updated
- 20 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Protective Efficacy of BCG Vaccination Against Controlled Human Malaria Infection
- ClinicalTrials.gov ID
- NCT02692963
- Acronym / sponsor ID
- BCG-EHMI / BCG-EHMI
- Conditions
- Malaria, Plasmodium Falciparum
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- Oct 2016 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 26 Feb 2016 (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.
The Bacillus Calmette-Guérin (BCG) vaccine, a live attenuated Mycobacterium bovis vaccine, has been used to prevent tuberculosis for almost a century, and it is still the most used vaccine in the world. There is also circumstantial and indirect evidence that BCG vaccination can protect against malaria. Investigators hypothesize that BCG vaccination can offer protection against malaria in the Controlled Human Malaria Infection (CHMI) model.
A total of 20 healthy male and female volunteers will participate in this randomized, single-blind clinical trial. Volunteers will be randomized to receive either BCG vaccination (BCG vaccine SSI) (group 1, n=10) or no treatment (group 2, n=10). Five weeks after vaccination of group 1 volunteers, all volunteers will undergo a CHMI administered by the bites of five P. falciparum infected Anopheles mosquitoes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BCG vaccination | Experimental | Biological: BCG vaccination |
| Control | No intervention | – |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Subject is aged ≥18 and ≤35 years and in good health.
- Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
- Subject is able to communicate well with the investigator and is available to attend all study visits.
- The subject will remain within the Netherlands during the challenge period, not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period.
- Subject agrees to inform his/her general practitioner about participation in the study and to sign a request to release by the General Practitioner (GP), and medical specialist when necessary, any relevant medical information concerning possible contra-indications for participation in the study.
Key exclusion criteria (18 listed)
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following.
- 1.1 Body weight <50 kg or Body Mass lndex (BM l) <18 or >30 kg/m2 at screening. 1.2 A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of >5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.
- 1.3 A medical history of functional asplenia, sickle cell trait disease, thalassaemia trait/disease or G6PD deficiency.
- 1.4 History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
- 1.5 Screening tests positive for Human immunodeficiency Virus (HlV), or active Hepatitis B Virus (HBS) or Hepatitis C Virus (HCV).
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 |
|---|---|---|
| BCG vaccinationBCG vaccine InterVax | Biological | BCG vaccination |
Primary outcome
Frequency and magnitude of adverse events
Time frame: day of BCG vaccination until day 37 after malaria challenge infection
Adverse event collection and routine safety and hematology laboratory evaluations will be conducted from the day of BCG vaccination until day 37 after CHMI.
Time to blood stage parasitemia detectable by qPCR
Time frame: day 1 - 21 after malaria challenge infection
The effectiveness of BCG vaccination to protect against CHMI will be evaluated by quantitative PCR.
2 secondary outcomes
Changes in cellular (innate and adaptive) immune responses
Time frame: inclusion until day 120 after malaria challenge infection
Changes in plasma cytokine levels
Time frame: inclusion until day 120 after malaria challenge infection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2017.
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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.
Robert Sauerwein, Prof. principal investigator
Radboud University Medical Center
Mihai Netea, Prof. principal investigator
Radboud University Medical Center
Jona Walk, MD study director
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BCG vaccination in people with Malaria and Plasmodium 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 9 inclusion and 18 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: finished, as of the sponsor's last update on 20 Apr 2017. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Frequency and magnitude of adverse events (time frame: day of BCG vaccination until day 37 after malaria challenge infection). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Apr 2017.