Local testing is part of larger trial

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

Kids and teens can help develop a vaccine against Lyme disease that's being studied in a clinical trial available in Syracuse.

My guest, Dr. Kristopher Paolino, is leading that study. He's an assistant professor of medicine and of microbiology and immunology at Upstate, and he specializes in Lyme and other tick-borne diseases. Welcome back to "The Informed Patient," Dr. Paolino.

Kristopher Paolino, MD: It's my pleasure.

Host Amber Smith: Tell us about this investigational vaccine, VLA15. I understand it's made by Pfizer.

Kristopher Paolino, MD: Actually, it's made by a company in Europe called Valneva, and Pfizer and Valneva joined in an agreement back in, I think, 2020 to help co-develop the vaccine and push it through the final stages of development.

Host Amber Smith: So is this a new medication?

Kristopher Paolino, MD: Technically it is. It is based off of the old Lyme vaccine that many people don't remember, that was FDA approved back in, I think it was the late '90s, early 2000s. It's got some subtle changes to the development of the vaccine that make it a little bit different, so technically it is a new vaccine.

Host Amber Smith: How is it designed to work?

Kristopher Paolino, MD: It's interesting. So most vaccines that we receive, we receive the vaccine, and then our body mounts an immune response, so that if we were to be infected or come in contact with an infection, the antibodies will attack those viruses or bacteria and help prevent the infection from developing. That's what we see with flu and COVID vaccines.

This is actually a very unique vaccine in the sense that it targets the outer surface protein A, which is expressed on the bacteria of the Lyme bacteria, inside the midgut of the tick. So what happens is you get the vaccine, you develop these antibodies, and then, say you're out walking around, and you go to the park, and you get bit by a tick.

Those antibodies in your blood will be taken up by the tick in the blood meal and inactivate, or prevent, the bacteria from spreading from the tick to you, so it's almost more of a transmission-blocking vaccine, so it's definitely unique in that sense.

Host Amber Smith: That is interesting. Now, has it been shown to be safe and effective already?

Kristopher Paolino, MD: Yep. So again, it's similar to the vaccine that we had back in the late '90s, which was shown to be effective and overall was felt to be very safe as well. This vaccine has already gone through Phase 1 and Phase 2 studies, and it's already in the midst of a larger, Phase 3 study that started back in August of 2020.

It has been shown to be safe, based on those earlier studies, and this major Phase 3 study is going to look to show effectiveness of how well it prevents people from getting Lyme disease.

It did show in the Phase 2 studies that it had a very strong immune response. So the hope is that when people get this vaccine, it will help prevent Lyme cases from developing if you're bitten by a tick.

Host Amber Smith: Now, why is it important to find people age 12 to 17 who are willing to be test subjects for this?

Kristopher Paolino, MD: Whenever we have a new vaccine that comes out, we always want to make sure that it's safe for all populations. So with the larger Phase 3 study, they are enrolling pediatric populations all the way up through adults.

This study, which is kind of an offshoot of that other study, even though it's a separate protocol altogether, is a Phase 3 study just looking at the safety in pediatric populations, so the study will be looking at 5- to 17-year-olds, and they'll break it down between two different groups.

There'll be five- and 11-year-olds in one group, and then 12- and 17-year-olds in the other group. And we're basically just going to be collecting data on any side effects, adverse reactions that anybody might come across, typically things like arm soreness, redness in the arm, fevers, fatigue, headaches, those kind of things, after vaccination.

Host Amber Smith: Does Lyme disease affect kids the same way that it does adults, potentially?

Kristopher Paolino, MD: It does. there may be some subtle differences. Lyme can affect anybody. There may be a slightly increased risk in children. There have been a few studies to indicate that age ranges between 5 and 9 have a higher peak in number of cases, but overall, anybody can get Lyme.

There may be some differences in how they present. So, younger children might have more irritability. They may be more likely to have fevers, potentially more likely to have joint pain or swelling because they may not identify the tick on them until very much later, when they develop the longer symptoms of late disseminated Lyme disease.

Host Amber Smith: So I wanted to ask you to go over what Lyme disease is and the damage it can do. You mentioned some of the, I guess, more common symptoms, the fevers and the joint pain. Are there other telltale signs that people should be on the lookout for?

Kristopher Paolino, MD: Sure. There are different stages, if you will, of Lyme disease.

So, there's early localized Lyme disease. That's the bullseye rash that everybody is aware of. So, within anywhere between three days and maybe 30 days of a tick bite, you can develop an expanding red rash. it doesn't always look like a target rash or a bullseye. It could be just a confluent red rash that develops from the tick bite and usually gets to the size of a softball, or much larger in some cases, that might be associated with flu-like symptoms, aches and pains, chills, fevers, headaches. Fevers can get quite high in some cases. And then as the infection kind of progresses, if somebody maybe doesn't have those symptoms or doesn't have the rash initially to recognize Lyme, they can go on to develop other manifestations.

Early disseminated cases would include things like heart involvement or Lyme carditis, where it can cause inflammation in the heart, can cause heart abnormalities in terms of how well your heart is able to conduct electrical activity. And people can get very slow heart rates that can be potentially life threatening.

Neurologic infections, or Lyme meningitis, otherwise known as neuroborreliosis, is another early disseminated, presentation. People can have really severe headaches. They might have problems with bright lights, neck stiffness, as well as all the other typical flu-like illness symptoms that people can develop.

And then there's also late disseminated infections where you can have Lyme arthritis, where you get that joint swelling, joint pain, typically in the knees, but really any joints can be involved in the cases of Lyme arthritis, and this is something that occurs several months, generally, after the initial tick bite.

Now, on top of that, there's also more of a long-term process that can happen, and the reasons for these symptoms are still kind of up in the air. Some people hypothesize that there's a persistent infection. Some others hypothesize that there's neurologic damage or joint damage or maybe autoimmune development.

There's a lot of different reasons floating around. There's a lot of data and science that's being done to try to identify that, but these patients can go on to have chronic fatigue, chronic headaches and migraines. They can have cognitive issues where they feel like they have brain fog. They might have chronic joint pains, numbness and tingling in their hands and their feet. There's a whole variety of symptoms that people can suffer from. So if we can prevent those people from getting Lyme in the first place, I think it'll help with a lot of the suffering that people deal with.

Host Amber Smith: Are you able to diagnose that someone has Lyme with a blood test?

Kristopher Paolino, MD: Yep. That's the way that we diagnose it.

I've talked about this issue in the past. Early in the case of Lyme, the tests are not super helpful. So if you have like a bullseye rash, I generally wouldn't recommend ordering a blood test in this region. I would just treat for Lyme disease because you may only have a positive test in maybe 20% to 40% of those cases because our bodies need time to develop the antibodies, rather than identified in these blood tests to make the diagnosis. The later you get in the infection, the more time your body has to develop the antibodies, so by the time somebody has late disseminated infection with joint pains and joint swelling, generally everybody's going to have a positive test at that point, so the longer you've had it, the more severe the disease, the more likely you're going to have an immune response. It's not 100%, but it's close to it.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith.

I'm talking with Dr. Kris Paolino. He's leading a study at Upstate Medical University of an investigational vaccine against Lyme disease, and he's recruiting people age 12 to 17 to participate. Anyone who is interested can learn more at 315-464-9869 or by sending an email to trials, that's [email protected]. Now, what type of people are you looking for in the trial? Ages, genders, races?

Kristopher Paolino, MD: Primarily, we are going to be looking at the 12- to 17-year-old group. We are not participating in the younger age group, so it's a smaller cohort of patients that we're going to be identifying and including. So 12- to 17-year-olds, any gender, any race, would be enrolled in the study.

Host Amber Smith: If someone has had Lyme disease before, are they disqualified from participating?

Kristopher Paolino, MD: This is a great question. This is a yes-and-no answer.

If you have had Lyme disease diagnosed, of any sort, in the past three months, you are not enrollable in this study, all right? Now if you had a bullseye rash four months ago, then you would be allowed in the study. The people that are definitively not included are people who have those later-onset manifestations of Lyme disease.

So if you've been diagnosed with Lyme carditis, the heart involvement, Lyme meningitis or Lyme arthritis, those are typically the Lyme manifestations that are not going to be enrollable.

Host Amber Smith: Are there other things that would disqualify someone from participating?

Kristopher Paolino, MD: I think anytime we're doing a vaccine study, we generally don't enroll people who have any immunodeficiencies, so people going through cancer therapy, people who have had transplants of any sort, people who are on long courses of steroids, we generally will not enroll those patients if we're going to be checking maybe the immune response down the road.

The other thing that's probably more important, just given the timing of the study, is anybody who's had a tick bite in the past four weeks,we won't be enrolling those individuals.

But if you had a tick bite, say, last year or six months ago, assuming you didn't develop one of those manifestations of Lyme I mentioned, you'd be enrollable in this study.

Host Amber Smith: And how many people are you looking to enroll? Because this is one of several sites, right?

Kristopher Paolino, MD: Correct, yeah, so they're looking to enroll globally, for the entire study, about 3,000 children between the ages of five and 17.

We are trying to enroll as many as possible. The goal is to try to get this study filled and done and completed as quickly as we can, so we can get that data, so that we can then have Pfizer go ahead with Valneva and try to get that FDA approval as soon as we can.

Host Amber Smith: Will every participant receive the vaccine?

Kristopher Paolino, MD: Another good question. The answer is no. This is a randomized, controlled study. Most studies that are like that are going to be in a one-to-one ratio, so for every person that comes in, one person will get the placebo (an inactive dose, used for comparison in testing), one person will get the vaccine. This study is a bit different because it's more of a three-to-one ratio.

So if four people come in for enrollment in this study, three of them may get the vaccine, one of them would get the placebo. So there's a good chance that you will get the vaccine, but we won't know who gets the vaccine until much, much later in the study.

Host Amber Smith: So at the end, after everything's completed, will the people find out whether they got the vaccine or the placebo?

Kristopher Paolino, MD: The protocol does not specify whether or not they're going to unblind people. My guess is that will be the case once the study is completed, but not until then. So people won't probably know if they received the vaccine or not until well after the study is completed and closed, just to try to avoid any bias in the study, in the data.

Host Amber Smith: What's involved at the visits?

Kristopher Paolino, MD: It's actually pretty straightforward. There'll be a screening visit that will bring people in, we'll discuss their medical history, tick exposures, things that I had already mentioned in terms of the inclusion/exclusion criteria. And then, if they are found to be eligible for enrollment, we would be able to do the vaccination.

Vaccinations are going to be on multiple different dates throughout the course of the study. So there's going to be the day zero injection, and then there'll be another injection at the two-month mark, a third injection at the six-month mark and then a fourth booster injection at the 18-month mark.

And at each of these injections, you'll receive a vaccination, but there are no blood draws as part of this study, so people won't be getting those typical tubes of blood taken for any additional testing. And we're primarily just going to be looking at any kind of side effects that people describe to the investigators.

And we'll be collecting that data through the use of an e-diary that people can download on their phone as an app, and they'll fill it out on a frequent basis for the purpose of the study.

Host Amber Smith: So they need to be willing to commit to 18 months, roughly, of time?

Kristopher Paolino, MD: Actually 24 months, so there'll be an additional phone visit at the 24-month mark, and I believe there's also a phone visit at the 12-month mark.

Host Amber Smith: Now, I understand the participants are volunteers, but do they receive any sort of compensation?

Kristopher Paolino, MD: Yep. As of right now, my understanding is that it will be a $100 compensation per visit in the clinic, and that will be for their time, their effort and participation overall.

Host Amber Smith: Being that these people are 12 to 17 years old, are they going to need their parents' permission in order to participate?

Kristopher Paolino, MD: We'll do a consent and assent process, so we need consent from both of the parents or legal guardians, as well as, assent, or consent, in a sense, to participate from the patient themselves.

Host Amber Smith: What happens if a study participant gets a tick bite or contracts Lyme disease during the trial?

Kristopher Paolino, MD: That will be something that we will collect and will identify, similar to monitoring for other side effects and other things. We'll want to know if somebody developed a tick bite, if they developed Lyme disease or other tick-borne diseases and will collect that data. But they'll be receiving care through their primary care providers.

Host Amber Smith: Do you think that the things you learn from this age group is going to apply to other age groups as well?

Kristopher Paolino, MD: It'll add to the data that's being developed. I think, from the prior studies in Phase 1 and Phase 2, we have a good base of data from those trials.

I think the big Phase 3 study that's already ongoing is going to be where we're going to see a lot of this data, and this additional study is just going to add to it.

Host Amber Smith: Well, Dr. Paolino, thank you so much for telling us about this.

Kristopher Paolino, MD: Thank you for having me.

Host Amber Smith: My guest has been Dr. Kristopher Paolino, an assistant professor of medicine and of microbiology and immunology at Upstate. And for more information about this study, call 315-464-9869 or send an email to [email protected].

I'm Amber Smith for Upstate's "HealthLink on Air."