The Multi-Study Phase Three trial of the malaria vaccine will involve 16,000 children and take place in 11 research centres in seven African countries.  It is aimed at testing the efficacy of the RTS,S vaccine for the treatment of malaria.  RTS,S h has 50 percent potency. 

Kintampo Health Research Centre and Agogo sites embarked on a joint Phase 2 study in 2006 to ascertain the Safety and Protective ability of the vaccine in children.  The two Phase 2 trials conducted by these sites involved 540 children aged five to 17 months. 

Eyes on Malaria spoke with Dr Seth Owusu-Agyei, Director of the Kintampo Health Research Centre, on the new developments:

What do the Phase 3 trials entail?
This phase is a pre-licensure one, meaning if the results are good enough, other independent bodies will be looking at the results and deciding whether or not the vaccine is good enough to be given internationally.

How many children are involved?
We plan to recruit 1,200 children.  The first group will involve those aged five months to 17 months.  They will be recruited in the first six months and be given three doses of the vaccine within a two-month period. They will be followed up for two years.  They will immediately be followed by 200 others, who will receive the vaccine between six weeks and 10 weeks of age and will be followed the same way.  At the end of the day, what we are interested in evaluating is how many clinical malaria episodes are averted.
 
We will then say that because the child took this malaria vaccine, the number of malaria attacks the child would have had has reduced.  The other thing we will be interested in looking at is this: Even if the child should go down with a malaria attack, how severe will the attack be? This vaccine has been shown to be able to reduce the severity of the malaria attack.  These are the two main outcomes we will be interested in.

Having the opportunity to access 1,200 children in this trial gives us the chance to look at more safety data.  If we are lucky to come up with results that show that this vaccine is able to protect the children half the time, I am pretty sure that it won’t be very difficult for the decision makers to take this up and integrate it into the routine vaccinations that are given to children.  If we get results that are not very convincing, however, we will need to do a lot more work in order to come up with a malaria vaccine.

Will children who have been involved in previous studies be considered?
No, the rules are that any child who has been involved in earlier trials of this malaria vaccine will not be eligible.

Some mothers say they are in the study because of the care you give to study participants. 
We try to provide the best care we can.  Immediately a child is screened, enrolled and receives the vaccine, the child is fully our responsibility. We have to ensure that anytime the child is unwell, we provide the necessary care.  This will involve transporting the child from wherever he/she lives to the health facility, giving a qualified clinician access to the child, going through the necessary laboratory processes and doing whatever it takes to treat that child and ensure that the illness is resolved.

How will you assess the previous studies?
Earlier studies carried out were designed to look at the safety of the vaccine.  I can categorically say that the results we generated showed that the vaccine is very safe.  The other parameter we were interested in was to look at the protective capabilities of the vaccine that also came out very strong.  We didn’t carry out this work in isolation. Other institutions were involved in the trials that are ongoing and the results that they generated confirmed what we generated in Kintampo.  So we scientists are convinced that the results we are going to come up with in this phase will go to augment what we have already and make it possible for this vaccine to be registered.

Research involves observing some form of ethics.
I think I will put all the groupings together and call them the regulatory committees. This will involve the ethics or the ethics committees that we deal with, the Food and Drugs Board and the Ghana Standards Board.  They all come together.  The ethics committees look at the content of the work we want to do. Your trial should show convincingly that what you are doing is for the good of the child and that the benefits far outweigh the risk that the child will have to go through. Only when they are convinced will they give us the go-ahead to use the child or embark on the trial. 

The ethics committees that we will deal with are within country—the Kintampo Health Research Centre Ethics Committee, then the Ghana Health Service Ethics committee.  Because we collaborate with Americans in these, we have the Western Institutional Review Board, which will also look at it from their perspective.  And because we collaborated with the London School of Hygiene and Tropical Medicine, they also have an ethics committee that will give approval before we carry on with the work. 

The role of the Food and Drugs Board is to also ensure that the vaccine to be used has all the required documentation and safety information, and that the manufacturing parameters are good enough to be used before importation into the country is allowed.  The Ghana Standards Board also come in by assessing the equipment used for the work. This means fridges in which the vaccines are stored, the weighing scales and all other equipment used passes through the Ghana Standards Board before we are allowed to use it.  We are happy to work with all these bodies because if we are at fault in any way, they will be there to help us get things right.

It is not only Ghana that has started Phase 3. Which are the other countries and at what point it is going to end?
There are 11 institutions that are involved in Africa, and these sites are in seven countries.  We have the Kintampo site and a site in Agogo that is also used by colleagues from the school of medical sciences and Kumasi centre for collaborative research work.  There is one site in Burkina Faso, two sites in Tanzania, three in Kenya and a site each in Mozambique,  Gabon and Malawi. 

Can you tell us something good about what you are doing to give us hope?
Malaria has always been the biggest health challenge for Africa.  We do have some control methods, including prompt and appropriate treatment, use of treated bednets, environmental controls such as indoor spraying and repellants.  They work to some extent but we all know what vaccines have down to eradicate other diseases.  If this vaccine works, it will reduce the health problems we have.  It is not the all-in-all vaccine because its potency has been shown to be about 50 percent, but if we should translate that into reducing the number of contacts that these children make with our health facilities every year, there will be lots of savings on drugs, health personnel time and several other indicators. 

If we took into consideration that children will progress from clinical malaria to severe forms and die, then about half the deaths that we have been registering in our communities will have been stopped. That is going to be exciting. I believe we will get the vaccine, I believe the results will be convincing enough for international bodies to make a decision. If that happens, Ghana stands to benefit a lot.

When the vaccine is licensed, is there a guarantee that there will be enough for Africa?
This is what we scientists have been fighting for. In all the discussions I have been involved in, the manufacturers of these vaccines and those providing funding—GlaxoSmithKline and the Path Malaria Vaccine Initiative—have made a commitment to make this vaccine available so that the mother who is making contact with any of our health institutions can get her child vaccinated free of charge. 
           
As scientists and investigators, we are extremely grateful for the support we have received from our sponsors and collaborators.  Because of this support, we are making good progress.  They should continue to support us so we can take this process to the logical conclusion.

Kintampo has been rated very high in terms of research. How did it get that way and how do you feel about it?
Getting Kintampo here has not been easy, and we are doing all we can to make sure that whatever we are doing is successful at the end of the day.  The level of commitment among  the scientists doing not only the malaria vaccine work but all other studies, including the Maternal Child Health Studies and Mental Health Studies is what has taken us to the level that we are. If the scientists continue the same way, the sky will be the limit for Kintampo.