Safety and Protective Efficacy of BCG Vaccination Against Controlled Human Malaria Infection

NCT02692963 | Completed Phase 2

• 3 other identifiers: BCG-EHMI2015-005735-40NL56222.091.15
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  day 1 - 21 after malaria challenge infection

Secondary Outcomes (2)

• Changes in cellular (innate and adaptive) immune responses

  inclusion until day 120 after malaria challenge infection

• Changes in plasma cytokine levels

  inclusion until day 120 after malaria challenge infection

Study Arms (2)

BCG vaccination

EXPERIMENTAL

Biological: BCG vaccination

Control

NO INTERVENTION

Interventions

BCG vaccination BIOLOGICAL

BCG vaccine InterVax

BCG vaccination

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• A medical history of functional asplenia, sickle cell trait disease, thalassaemia trait/disease or G6PD deficiency.
• History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
• Screening tests positive for Human immunodeficiency Virus (HlV), or active Hepatitis B Virus (HBS) or Hepatitis C Virus (HCV).
• 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.
• 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.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
• Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud university medical center

Nijmegen, 6525 GA, Netherlands

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Robert Sauerwein, Prof.

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Mihai Netea, Prof.

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Jona Walk, MD

  Radboud University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2016
• First Posted: February 26, 2016
• Study Start: April 1, 2016
• Primary Completion: October 1, 2016
• Study Completion: February 1, 2017
• Last Updated: April 20, 2017

Record last verified: 2016-08

Locations

NL (1)