Media release

University of Auckland

10 March 2004


Meningococcal B vaccine Trial Results Continue to be Encouraging


Findings released today from the Meningococcal Vaccine Trials show further evidence that the vaccine is safe and vaccinated toddlers mount an immune response against New Zealand’s epidemic strain of meningococcal disease. These are encouraging results, according to principal investigator Professor Diana Lennon.

The trials, conducted by the University of Auckland in partnership with the Ministry of Health and Chiron Corporation of California are progressing well. New Zealand is still in the grip of a Meningococcal epidemic which has resulted in over 5000 cases and over 200 deaths since 1991. The results of the MeNZB™ vaccine were presented today at the WHO/UNICEF Workshop on the expanded programme on Immunisation in the Pacific in Auckland.

This arm of the continuing clinical trials involved 300 toddlers from all over Auckland who were aged between 16 to 24 months. They were each given three doses of vaccine at six weekly intervals. Their blood was tested at four to six weeks after each immunisation and shows a good antibody response. The vaccine was well tolerated with some side effects such as soreness at the vaccine site passing after a day or two for most toddlers.

The principal investigator of the trials, Professor Diana Lennon, who is Professor of Community Paediatrics at the University of Auckland, says she is pleased that the vaccine is proving to be safe and immunogenic in the people tested so far. “This vaccine offers the best hope for overcoming an epidemic which carries such a huge cost, especially with our babies and young people”, she said.

Results of clinical trials involving adults released last August indicated that the MeNZB™ vaccine was safe and likely to be protective from the strain of meningococcal disease that is causing New Zealand’s epidemic. The part of the trials involving toddlers is just one part of a long and rigorous evaluation looking at differing sectors of the New Zealand population. Trials involving adults, children aged 8 to 12 years of age, toddlers aged 16 to 24 months of age and babies aged 6 to 8 months of age have been completed while trials involving babies at 6 to 10 weeks of age began in January.

The recruitment of the volunteers for the children’s trials has been a long process, enlisting the support of Plunket, Maori and Pacific health providers, public health, school and community nurses and general practitioners. Pending regulatory approval, the national immunisation programme which will aim to vaccinate all New Zealanders aged 19 years and under is expected to begin in South Auckland in the middle of the year.


Ends

About Clinical trials

What is a clinical trial, why is this process necessary and what is the purpose?

• A clinical trial is a research study to answer specific questions about vaccines, new therapies or new ways of using known treatments. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people.
  

How is the vaccine’s immunogenicity being tested (i.e. have participants been exposed to meningococcal disease?)

• There are two ways in which this is being measured: both during the studies and during the roll-out (the roll-out refers to the stage when we hope to offer the vaccine to all people under 20 years of age nation-wide where the effect of the vaccine on the epidemic will be assessed).
• Participants are not being exposed to meningococcal disease (any more than the general population).
• During the studies, each participant has a blood test several weeks after vaccination. This blood test measures antibodies against the meningococcal bacteria. This is how we measure whether we expect the vaccine to work. This antibody test has previously been shown to be a good measure (or ‘correlate’) of effectiveness, in other international studies.
• During the roll-out, when the vaccine is given to the wider population, there will be ongoing evaluation of its effectiveness in preventing meningococcal disease. This will not involve blood tests but instead will look at rates of meningococcal disease before and after vaccination.

What are the key steps in the clinical trial process (e.g. timeline)?

• In any clinical trial process, including for vaccines, the first step is usually a phase I study, which involves testing the vaccine in a small group of healthy adults. This initial phase is to look at safety, determine a safe dosage and identify side-effects. For the NZ meningococcal B vaccine, this study began in May 2002 and has now been successfully completed. The safety and antibody information gained from this study informs the next studies
• The next step usually consists of a phase II study, which involves a larger group of people, to find out more antibody and safety information. In this case, there has been three phase II studies, involving school children, toddlers and infants, to ensure that the vaccine is safe and has good antibody results in all age groups. The early infant study is still continuing. The school children study began in October 2002 and the toddler study began in February 2003. The antibody and safety information from these studies informs the next phase.
• The next step is usually a phase III or IV trial, which involves giving the vaccine to a large number of people, either as a ‘randomised controlled trial’ or as an evaluation of the vaccine effectiveness. To reach this stage, this vaccine must have been already shown to be safe and have good antibody results. However, during this stage there is still monitoring to ensure that the vaccine is as safe as expected, and there will also be monitoring to assess how well it is working.
• In usual situations where a new medicine is being studied, this process can take up to 15 years or more. In New Zealand, we have an epidemic to battle, so we face the challenge of conducting this entire process in just a couple of years, while also meeting the same high standards in ensuring the safety and effectiveness of the vaccine.
• Other meningococcal B vaccines have been given in over 40 million doses, primarily in Latin America, with no serious unexpected reactions recorded.

How does the vaccine work?

• This vaccine, like most others, is given by injection. The principle by which this vaccine and other similar vaccines work is the same. Meningococcal disease is caused by meningococcal bacteria. This vaccine contains elements (‘antigens’) that are present in meningococcal bacteria. The body’s immune system responds to these antigens, so that the next time such antigens are encountered (such as exposure to real, live meningococcal bacteria) the immune system ‘remembers’ and recognises these bacteria, and mounts a swift response. This immune response is what protects immunised people against the disease.

Where is the vaccine made?

• A strain-specific trial vaccine has been produced by Chiron Corporation in collaboration with the Norwegian National Institute of Public Health (NIPH), which developed a similar vaccine for a group B meningococcal epidemic in Norway in the 1990’s. [Ministry of Health media Fact Sheet 4, ‘The Meningococcal Vaccine Strategy’]
• Chiron will produce the vaccine using the same technology used to produce the vaccine in Norway.

What is in the vaccine and what tests have been done on the vaccine prior to the clinical trials?

• The active components in the vaccine are parts of the meningococcal bacterium, broken up into small bits. These bits are primarily protein from the outer wall of the bacterium. There are no live meningococcal bacteria in the vaccine and it is not possible to catch the disease, or to become a carrier of the disease, from the vaccine.
• The vaccine undergoes physicochemical testing to ensure that it contains the ingredients that are detailed by the manufacturer and that there are no harmful ingredients. Also, a similar vaccine made using the same technology in Norway has been given in over 300,000 doses in Norway, most of these during controlled studies, with an excellent safety and effectiveness profile. Other meningococcal B vaccines have been given in over 40 million doses, primarily in Latin America, with no serious unexpected reactions recorded.

Why are parts of the trials being conducted only in South Auckland?

• The school children study involved part of South Auckland only. The intent was to choose an area that was well-defined geographically (for logistical reasons) that also represented the children who were at risk of meningococcal disease, both in terms of location and ethnicity.
• The other studies - adults, toddlers and infants - were conducted throughout Auckland.

How long will you continue to monitor trial participants?

• The participants are closely monitored after each vaccination for 30 minutes. After this we keep contact with participants over the next 7 days to check that they are well. There is also a 24-hour 0800 number that is available for families who have any concerns. If participants agree, their family doctor is informed of their involvement with the study, enabling the GP to report any possible long-term adverse events. There will also be an active surveillance system monitoring adverse events that result in admission to hospital during the roll-out (the phase in which the vaccine is offered to all children in the general community). An international safety monitoring board will be in place for the use of the vaccine in the roll-out.

What side effect would have been considered serious enough to suspend or stop the trial altogether?

• Any adverse events (i.e. participants becoming sick) are recorded, whether or not the problem seems to be related to the vaccine. Any serious adverse events, such as hospitalisation, are taken particularly seriously and are notified within 24 hours to Chiron and those overseeing the studies. A decision can then be made as to whether the problem is related to the vaccine, and then whether the study should be suspended. The regional ethics committee is also informed of all serious adverse events. There have been no serious problems thought to be related to the vaccine in the studies so far.

What happens after the clinical trials?

• The information obtained from the clinical trials will be presented to the New Zealand medicines licensing agency, Medsafe, which will examine the safety and antibody information and recommends whether the vaccine may be offered to the whole country. The strategy is to offer the vaccination to all those aged under 20, as this is the age group at highest risk.

Who makes the final decision on whether the vaccine will be used or not?

• The data obtained from the clinical trials will be submitted to Medsafe, which will recommend to the Minister of Health whether the immunisation programme should proceed and any limitations surrounding it. The Director-General of Health, acting on delegated Ministerial authority, will then make the decision on whether to proceed with the programme. Medsafe is an independent regulatory body and the Ministry cannot influence the licence parameters.
• Before the vaccine can be used in the clinical trials, the Standing Committee on Therapeutic Trials (SCOTT), as well as regional ethics committees, must evaluate and approve the vaccine production and the design of the study.
  

If the clinical trials prove the vaccine will be safe and effective, what happens?

• If the vaccine is recommended by Medsafe, through evaluation of the safety and antibody data obtained from the studies, the vaccine will be offered to under-20-year-olds throughout New Zealand in a staged ‘roll-out’.