Full Q&A Transcript: The Seattle Clinical Malaria Trials Center
- How do you see this research changing the way our organization works to prevent malaria?
Answer: Human challenge trials provide a rapid and safe clinical trial route to evaluate Candidate Vaccines and drugs intended to combat malaria. Our organization brings together all the medical and research infrastructure necessary to conduct these studies and obtain cutting edge insights that help us down select promising candidates for further development. Our organization works with partners in Seattle and globally to focus on products that have the most potential impact in the fight against malaria.
- How do you think your research will be impactful for people in sub-Saharan Africa?
Answer: Immunity to malaria and ongoing exposure to malaria are realities of living in malaria endemic regions. These factors complicate clinical trials conducted there, even though it is necessary to conduct such trials. Human challenge trials in Seattle remove some of those potential confounding factors since we can recruit and enroll participants who have never been exposed to malaria parasites. We are also working on trial designs that would recruit people who previously lived in Malaria endemic regions so that we can study their responses as well under these highly controlled conditions. The goal is that we could more successfully and more quickly identify promising drug and vaccine candidates so that they could go to the larger and more time-consuming studies in field settings in malaria endemic regions. Our intention is that the human challenge model will screen unsuccessful drugs and vaccines so partners in Africa and other endemic regions would spend more of their research time working with the most promising candidates.
- What are the goals for the MCTC in the next year? 5 years? And is there a way MPI can partner to help reach these goals?
Answer: We have One study that is actively enrolling in Seattle to evaluate a vaccine that is composed of attenuated parasites. This vaccine has already shown promise in previous clinical studies and we are working to refine our knowledge of this vaccine. In addition, we have several clinical trial concepts that are in development to better understand key aspects of immunity to malaria, which will help us work with partners to design better vaccines in the future.
Dr. Murphy’s lab is working on their own malaria vaccine concepts including one called prime and trap. This approach is intended to induce a long term protective immune response in the liver where the parasite resides after you are bitten by an infected mosquito. The Murphy Lab would very much like to progress one of their vaccine candidates to first in human studies in the next five years and we hope to be able to move that process forward at the Seattle MCTC.
- How has COVID-19 impacted trials at the MCTC?
Answer: In the initial part of the outbreak, much of our clinical trial activity for anything other than Covid was obviously shut down. Our research laboratories were fortunate to keep moving forward, as were those of partners nationally and globally. Because of this we have several vaccine candidates that are getting closer to clinical trials and those are some of the products that we are developing protocols for right now.
Covid had a bigger impact on malaria control globally and there are estimates and predictions that suggest that malaria will worsen in the near term because of efforts understandably being redirected to combat COVID-19. We hope that this is not a major setback for malaria control over the long haul, but it certainly highlights the need for ongoing prevention and a highly protective malaria vaccine.
- What translational benefits do you see from this work to other diseases or global health issues?
Answer: The controlled Human Malaria infection model is in many ways the envy of other human challenge models. We have decades of data showing that this is a safe clinical trial model and that the outcomes of these trials provide meaningful and actionable data about candidate drugs and vaccines. The malaria challenge model has encouraged development of other challenge models for other infectious pathogens. Human challenge studies have also been conducted in malaria endemic regions and this has resulted in capacity building of research infrastructure in many of those regions, which is highly desirable and a step in the right direction.
6. What stage of vaccine development and testing is the MCTC currently at? Is there a current project that is most promising?
Answer: Our center conducts phase 1 and phase 2 studies of vaccines and drugs. We are currently testing a vaccine manufactured by Sanaria, which is based on an attenuated whole organism vaccine that is given by direct venous injection. At the moment, this vaccine has the most clinical data of any product that we have worked with and represents a promising first-generation malaria vaccine.
7. If someone was considering becoming part of the MCTC is there anything you would want to say to them to encourage their participation?
Answer: We have more than 10 years of experience here in Seattle running human challenge studies. Challenge studies are safe, and the experience has been very meaningful to participants. There are always unknown risks about participating in clinical trials, but we provide the best and most complete information that we can to our participants and are not satisfied until their questions are answered. We have a tremendous and engaging team who would be happy to answer questions of prospective participants. Participants can find out information by going to our Seattle MCTC website, www.seattlemalaria.org, and click “Sign Up.”
8. Can you tell us what the general timeline / tasks of a study participant looks like?
Answer: When someone expresses interest in a clinical trial, usually they do so through an email or web form. The trial coordinator does a phone pre-screen to see if they might be eligible for a given trial. If they are a good candidate then we schedule an in-person screening visit to obtain informed consent, ask more questions, do a physical exam, and obtain blood to get some baseline labs. If all that information looks like the participant is eligible and the participant can commit to the clinical trial schedule, then they might be enrolled in the study.
When the study starts, the participants come in on each scheduled day. For a drug study for example we might give the drug, and then closely observe the participant over the next hours and days including sometimes having the participants stay in a hotel overnight where staff and other participants stay as well. This allows us to check in on participants on a frequent basis and often to collect repeated blood samples to be able to monitor the levels of the drug in the hours and days that follow administration.
Vaccine studies usually take place over a longer period because there are usually weeks to months between the doses given for vaccines. So, for example a participant might come in to receive the first dose, and then come back in the days that follow to give blood samples to monitor the right response of the immune system to the first dose, and then get another dose a few weeks or a month later, this might be repeated two or three times depending on the vaccine.
When we do malaria challenge, the participants come in perhaps a month after their last dose of vaccine or a few days before or after receiving a drug and they receive either mosquito bites or a small injection of preserved parasites that can cause an actual infection. In the days that follow we closely monitor the participants for signs of the infection in their blood using a sensitive PCR test and for symptoms that might indicate that they are developing a malaria blood stage infection.. Of course, if the vaccine or drug does its job then the participant does not have any sign of infection and the drug or vaccine dose is deemed to be a success. When someone does develop a blood stage infection then we inform them and treat them with FDA approved drugs that rapidly clear the parasites from their system. We follow up with the patients at additional visits to make sure that they continue to feel well and eventually we have a closeout visit that designates the end of the trial.
There can be relatively few visits let’s say five or six or there can be very intensive visits schedules with more than 30 or 40 visits during a clinical trial. For this reason, our participants must be very committed to the study and we have been very successful in recruiting such generous volunteers. Participants are also paid for their time as they progress through the trial. Except for a few days where the sampling is very intensive or in cases where people spend a few days in the hotel with the team, most participants are able to go about their daily business, go to work etc.
9. Are there ways to get involved or contribute to your work if you are not eligible or prefer not to be a study participant?
Answer: Social media is an excellent tool for recruiting participants and we would ask people who are interested in our work but cannot participate to perhaps follow us and spread the news about our recruiting efforts when we have active trials. It is also valuable for the public to be aware of the public health importance of malaria and other diseases like this and to advocate for support of these programs at the local, state, and federal levels (Click Sign Up at www.seattlemalaria.org).
10. What are the exciting next steps in research you plan to be taking?
Answer: The institutions in Seattle contributing to the generation of immunology results and world-class, and the analysis of this data is a high-dimensional computational challenge. That said, we have the expertise to interrogate these immune responses to find what may be most meaningful for future vaccine development. Dr. Kublin is exploring the T-cell receptors associated with protection, and Dr. Murphy would like to move forward with prime and trap Vaccines as noted above. Most exciting is seeing the enthusiasm of volunteer to either participate in our clinical trials or assist us in any other ways. It is a citizen driven scientific endeavor, and we are fortunate to be involved.
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