BCG Challenge Study of a Novel TB Vaccine (TB045)

What is the purpose of this trial?

Tuberculosis (also known as TB) is a disease caused by a bacterium (Mycobacterium tuberculosis). TB disease remains one of the top fifteen causes of death worldwide. BCG (Bacille Calmette-Guérin) is the only vaccine currently licenced for use against TB, but it is not always protective.

A new vaccine has been developed, which is called ID93/GLA-SE. It has recently undergone clinical trials to show that it can be given safely to healthy people. However, it is not easy to determine which TB vaccines will work well and which will not. In vaccine studies against other diseases, such as influenza and malaria, it is possible to experimentally infect volunteers with the disease in question to see if the vaccine being studied is effective. This is called a “challenge” and is possible where the disease being studied is self-limiting or where safe, effective and short treatment regimens exist. This is not the case with TB, which requires a minimum of 6 months of treatment with multiple medications.

We have developed a ‘challenge model’, where inhaled BCG vaccine is given as an infectious agent, to act as a mimic for TB infection. The BCG vaccine contains bacteria which are still alive but, because they are weakened, they do not cause disease in healthy individuals. As the BCG and TB bacteria are similar, studying how the body’s immune system responds to and “fights off” BCG can give us important information about how well this new TB vaccine might work. The purpose of this study is to understand more about the body’s immune response to the new vaccine and to show the safety of using an inhaled BCG “challenge” to study new vaccines.

FAQ

What is the novel TB vaccine (ID93/GLA-SE)?

This novel vaccine has been developed in collaboration with the University of Seattle, USA. The vaccine is made from proteins which are found in or on TB bacteria. The vaccine does not contain any TB bacteria, and there is no risk of getting TB from it.

Is the novel TB vaccine (ID93/GLA-SE) safe?

The vaccine has been tested to find a safe dose and ensure that there were no significant side effects in seven trials in the USA, South Africa and South Korea. There were no serious side effects seen in these studies, some volunteers did have some mild symptoms and these are explained below and in the volunteer information sheet.

We will continue to collect information from volunteers in this study about anything that they experience after having the vaccination.

What is BCG?

BCG is a strain of the bacterium that causes infection in cattle. BCG is a live vaccine, meaning the bacteria in the vaccine are still alive but are weakened so that they do not cause TB disease.

Is the BCG aerosol “challenge” safe?

BCG is one of the most widely used vaccines in the world. Several billion people have been given the vaccine over the past 100 years and no serious side effects have been seen in healthy people. BCG is usually given as an injection under the skin and is not licensed as an aerosol inhalation. It has been given as an aerosol in three previous trials in the 1960s and 70s as well as in our group’s trial (TB041, TB043 and TB044).

The TB041 study has now finished with no safety concerns. TB043 and TB044 studies are ongoing and we are continuing to collect safety data, but there have been no safety concerns to date.

What does the trial involve?

Overall, the study will recruit 48 people into 2 groups. Depending upon which group they are in volunteers will be in the trial for 2 to 6 months and will have between 7 and 14 visits in total (see Figure 1).

The first group will contain 24 volunteers who will receive two doses of new (ID93/GLA-SE) vaccine and 8 weeks later an inhaled BCG challenge. Volunteers in the first group will have two visits to be given the vaccine and 4 other short visits to collect data and check for symptoms before having a BCG “challenge”. The second group will receive an inhaled BCG “challenge” only and no doses of the new vaccine.

The inhaled BCG “challenge” is given at one visit, and all volunteers will have a bronchoscopy 14 days later. There will also be four short follow up visits after the “challenge” to collect data and check symptoms.

For full details of all visits, please read the participant information sheet.

Figure 1. Trial timeline to show study visits

Is there any reimbursement for the trial?

Participants are reimbursed up to £1465 for their time, travel and inconvenience. Full details of the reimbursement can be found in the participant information sheet.

What are the advantages of taking part?

You will not necessarily gain any direct benefit from the study, however, during pre-study assessment you will get information about your general health including results from a medical examination, blood tests, urine tests, chest x-ray and lung function measurement. You may also get information about your health from the bronchoscopy.

However, these assessments are not carried out for diagnostic purposes and should not be considered a substitute for a doctor’s visit.

Information gained from this study may aid in the development of a more effective vaccination programme to prevent TB worldwide.

 Are there any risks from taking part in the trial?

The main risks and side effects of the proposed trial procedures are listed here.

Blood samples: drawing blood may cause slight pain and occasionally bruising

• ID93/GLA-SE vaccination: In the seven studies which have been completed to date on humans, the most common symptoms which people have experienced are; pain at the site of the vaccination, flu-like symptoms, headache and tiredness. These generally got better within 48 hours. There were no serious or life-threatening symptoms in any of these studies. Other common generalised symptoms expected with vaccination are low grade fever, nausea, reduced appetite and muscle pains.

• Aerosol inhalation of BCG: Inhalation is a safe route for giving medicines. To date 105 volunteers have inhaled the BCG across our TB041, TB043 and TB044 studies, with all side effects seen lasting a short duration only. Potential local side effects could include sore throat, tickly throat, shortness of breath, wheezing, chest pain, chest tightness, dry cough or cough with phlegm. Side effects could occur within the first few days of BCG infection and/or a week or two later. A doctor will be available throughout the “challenge” and the clinic room is equipped with oxygen and medications to treat any other symptoms.

• Bronchoscopy: This is a widely used routine medical procedure for diagnosing and treating illnesses of the lungs and airways and in research studies involving healthy volunteers. It will be performed in a dedicated NHS bronchoscopy unit at the Oxford University Hospitals NHS Foundation Trust by a consultant respiratory physician, who will discuss the risks with you before the procedure. For more information about this, please refer to the participant information sheet.

You will be monitored in clinic following both vaccination (if applicable) and aerosol BCG “challenge” for any reaction.

If you experience unexpected events or become concerned during the study you can call the emergency contact number given to you at enrolment. A qualified study doctor is available at all times on this number.

Please refer to the participant information sheet for full details of procedures and potential risks.

What will happen if I don't want to carry on with the study?

Participation is voluntary and you are free to withdraw at any time. If you withdraw we would not usually perform any more research procedures, although occasionally we might need to offer you a follow up visit, for example, to check a blood result.

With your permission, we would like to store the samples that we had already collected but if you did not want this we would discard them. If you choose to withdraw from the study, your standard medical care will not be affected.

For more details about the trial, see the participant information sheet

If you are interested in taking part, please click here to apply via the pre-screening questionnaire

If you have any other questions about participating then don’t hesitate to contact the trial team by email at vaccinetrials@ndm.ox.ac.uk