Clinical trial NCT02709278: Aerosol BCG Challenge Trial in Healthy UK Adults
Official title: A Clinical Challenge Trial to Evaluate Controlled Human Infection With BCG Administered by the Aerosol Inhaled Route Compared With the Intradermal Route in Healthy, BCG-naïve, UK Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: BCG
Aerosol
Tuberculosis
Challenge
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: University of Birmingham
First posted: 2016-03-16
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: TB041 is a clinical challenge trial primarily to evaluate the safety of BCG challenge administered by the aerosol inhaled route in healthy, BCG naive UK adults. The trial will also look to evaluate and compare the amount of BCG recovered from the lungs and from the skin, following challenge by either the aerosol or the intradermal route.

Detailed description: Mycobacterium tuberculosis (M.tb) is a pathogen found worldwide that infects humans causing tuberculosis (TB), a transmissible disease resulting in very high mortality and morbidity. It is estimated that a third of the world's population is latently infected with M.tb, and these people carry a 10% lifetime risk of developing active life-threatening disease. In 2013, there were 9 million new cases worldwide and 1.5 million people died of TB. Co-infection with human immunodeficiency virus (HIV) greatly increases risk of TB reactivation and death. TB diagnosis is challenging and drug treatment can be prolonged, harmful, costly and complex. For these reasons an effective vaccine is a global public health priority.

Currently to assess vaccine efficacy against TB there is no reliable alternative to large, randomized controlled trials. These efficacy trials for novel TB vaccines are challenging, time consuming and very costly. For other diseases, such as malaria, challenge studies have been informative. The development of a safe controlled human mycobacterial challenge model which would ultimately be validated against field efficacy studies could greatly facilitate TB vaccine development by being a guide for selecting which candidate TB vaccines to take forwards to large efficacy trials.

TB041 is a clinical challenge trial primarily to evaluate the safety of BCG challenge administered by the aerosol inhaled route in healthy, BCG naive UK adults. The trial will also look to evaluate and compare the amount of BCG recovered from the lungs and from the skin, following challenge by either the aerosol or the intradermal route.

Eligibility criteria: Inclusion Criteria:

* Healthy adult aged 18-50 years
* Resident in or near Oxford (CCVTM or OUH) or Birmingham (NIHR-WTCRF) for the = duration of the trial period
* Screening IGRA negative
* Chest radiograph normal
* No relevant findings in medical history or on physical examination
* Allow the Investigators to discuss the individual's medical history with their GP
* Use effective contraception (see below) for the duration of the trial period (females only)
* Refrain from blood donation during the trial
* Give written informed consent
* Allow the Investigator to register volunteer details with a confidential database (The - Over-volunteering Protection Service) to prevent concurrent entry into clinical studies/trials
* Able and willing (in the Investigator's opinion) to comply with all the trial requirements

Exclusion Criteria:

* Previously resident for more than 12 months concurrently in a tropical climate where significant non-tuberculous mycobacterial exposure is likely
* Participation in another research trial involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the trial period
* Prior vaccination with BCG or any candidate TB vaccine
* Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial challenge date
* Clinically significant history of skin disorder, allergy, atopy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
* Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents
* History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial agent, sedative drugs, or any local or general anaesthetic agents
* Pregnancy, lactation or intention to become pregnant during trial period Any respiratory disease, including asthma
* Current smoker
* Clinically significant abnormality on screening chest radiograph
* Clinically significant abnormality of spirometry
* Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy
* Current use of any medication taken through the nasal or inhaled route including cocaine or other recreational drugs
* Clinical, radiological, or laboratory evidence of current active TB disease
* Past treatment for TB disease
* Any clinically significant abnormality of screening blood or urine tests
* Positive HBsAg, HCV or HIV antibodies
* Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the volunteer at risk, affect the volunteer's ability to participate in the trial or impair interpretation of the trial data

Primary outcomes:
measure: Adverse Events (AE)
timeFrame: Up to day 168
Secondary outcomes:
measure: Quantification of BCG
timeFrame: At day 14
Other outcomes:
measure: Identification of cellular markers of immunity
timeFrame: Up to day 168
measure: Evaluation of aerosol BCG challenge vs intradermal BCG challenge
timeFrame: Up to day 168
Locations:
city: Oxford
country: United Kingdom
facility: Centre for Clinical Vaccinology and Tropical Medicine , University of Oxford
state: Oxfordshire
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals- John Warin Ward, University of Oxford
state: Oxfordshire
city: Birmingham
country: United Kingdom
facility: NIHR Wellcome Trust Clinical Research Facility, University of Birmingham
state: West Midlands
Study officials:
affiliation: University of Oxford
name: Professor Helen McShane
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Birmingham
name: Professor Paul Moss
role: PRINCIPAL_INVESTIGATOR
References: