I think it’s safe to say that any new medication that can potentially treat CLOVES Syndrome is quite a groundbreaking concept right now. It gives us hope that we are making progress. And for the last few months, I’ve have the opportunity to participate in one of the drug trials available: The ARQ Trial, which aims to determine whether Miransertib (a drug that inhibits the biological pathway that both AKT and PIK3CA mutations affect) can treat patients with overgrowth syndromes associated with these mutations.
The main reason I created my blog is to share my experience living with CLOVES/a rare disease, the ups and downs, and new experiences along the way. So talking about my experience on this drug trial is something I would like to share just so others can learn about what a drug trial might look like and its impact on my experience with CLOVES.
Disclaimer 1: Enrollment into this ARQ drug trial has ended, and since there has not been any significant change in reducing the size of measured lesions in participants so far, the goal of the trial shifted to safety efficacy for participants. This means the goal is now to prevent affected lesions/symptoms from progressing rather than aiming to effectively reduce the size of any affected lesions. We are truly hoping that by the end of this trial, it will be FDA approved if it is found to be helpful in any capacity.
Disclaimer 2: This blog post is completely based on my own personal experience with this particular trial. This post is solely meant to share my own experience and is not intended to give medical advice.
My journey starting this trial began with my genetic testing, which I needed to get in order to enroll into the trial. This was needed so the study sponsor had documentation that I actually have the genetic mutation PIK3CA (see previous blog post on genetic testing experience). Once I received that confirmation, my doctor educated me on the two drug trials available: ARQ (Miransertib – an AKT inhibitor) and BYL (Alpelisib – PIK3CA inhibitor). She suggested that the ARQ trial would be a more appropriate study for me because there were less reported side effects than the other drug trial, and I have more lipomatous tissue, which this drug targets (all of which I agreed with). The BYL trial was not enrolling patients yet at the time anyway, whereas the ARQ one was currently taking enrollments (this was back in the summer of 2020). The ARQ trial had a study taking place in Cincinnati, which is closest to me than any other trial location, and it reimbursed for travel expenses as well, which is an added bonus.
So the initial steps were taken over the next few months including signing releases of information to have my medical records sent to my team to be reviewed by my hematologist on the trial, signing consents for the study, and (virtually) meeting with the study nurse and hematologist. The team at Cincinnati is incredibly flexible, understanding, and kind which makes this experience all the more better. They worked with me on finding a good date to start, and we decided to schedule the appointments on Mondays since they worked best for me with my work schedule.
I officially started in September 2020. The trial schedule is broken down in cycles, and each cycle is 28 days. On the first day of each cycle, I have a study visit, and initially I had an appointment every 2 weeks until November 2020 for testing and close monitoring after first starting the medication. After November, the appointments progressed to monthly until January 2021. After January, my appointments spaced out to every 2 months, and now since my September visit, they are every 3 months moving forward. This study is intended to last up to 4 years. At that 4 year mark, we are hoping that there is enough valuable data to have this drug approved by the FDA if it has shown to prevent progression of symptoms for its participants.
Initially, I had asked if I could get my lab work done locally to avoid traveling so often, which I’m sure is a question others would ask as well. However, the trial requires that I see my hematologist on the trial in person every time I get my bloodwork at the specific appointments scheduled so all appointments have to take place where the study is taking place. These types of studies tend to have relatively strict protocol (which is understandable).
I went to my first official appointment (the “screening visit”) on September 21, 2020 with my mom, which was mainly to meet the nurse and hematologist on the study, sign consents, and complete blood work and vitals. Thankfully, my incredibly supportive mom accompanies me to every appointment. The next day on September 22, I completed a full body MRI. All of this data was then sent to the study sponsor to determine if I would be a good fit for the trial (basically to see if any lab work was abnormal, which fortunately it wasn’t).
Two weeks later, I was started on Miransertib. The medication dosage is based on height and weight so it was determined that I would take 30mg (three 10mg pills). This medication is to be taken with water, and then I have to either wait 1 hour after taking it before I can eat something or fast for 2 hours prior to taking it. So I found the best time to take it was as soon as I woke up in the morning.
The medication is from their “investigational pharmacy.” My team provides me with enough medication at each visit to get me through until the next visit, and then I have to bring the empty bottles back with me to each appointment to turn in and be replaced with new medication. So none of this goes through my own pharmacy.
When I started the medication, I was provided with a study binder that has a medical log in it. Every day, I have to log exactly what date and time I took the medication, how many pills I took, and specify if it was “whole or with semi-liquid” (if someone can’t swallow it whole, it can be mixed into food). I have to bring this binder with me to each visit, at which point my study nurse collects it to record and provides me with a new log.
In addition to covering the appointments, medication, MRI’s, and medical photos (which I’ll explain below), the study does also cover lodging and reimburse for travel and meals, which is a huge help since we have to travel 10 hours round trip for the study!
During my first few appointments while on the medication, they took blood work and completed EKG’s at very specific time intervals throughout the day so they ended up being quite long days. I think I got 2 EKG’s and 3 blood draws throughout the course of 8 hours at those first few appointments. The last couple of appointments, I’ve only needed one blood draw and sometimes an EKG so the visits have been much shorter (about 2 hours). Now that the trial goal has shifted to a safety factor, I no longer will have these long days so all appointments will be around 2 hours or less.
The day I started my medication, they also had a medical photographer take photos of the parts of my body that are affected by CLOVES with measuring tape on the areas (my legs/feet and abdomen/back). The photos are taken every 6 months to monitor progress so they were taken again at my visit in March, which marked 6 months into the trial, and again at my last visit in September, which marked 1 year into the trial (which is crazy to think about!). The sponsor mainly wants one lesion they consider to be measurable, which will then be followed throughout my time on the study to determine if there is any noticeable difference. This lesion of mine turned out to be the lipomatous tissue on my upper left back, and they are watching my leg and foot for any potential change as well. In addition to the photos, I also get a full body MRI every 6 months to monitor any changes.
Now, there were some blips in the beginning of this trial, which we later found out weren’t related to the medication. For the first 2 weeks on the medication, I was doing well and didn’t really notice a change. However, by the third week, I was starting to feel quite lightheaded, which persisted throughout the week to the point where I did not feel comfortable driving. This weird feeling got to the point where I felt like I was going to pass out (but never did). Initially, I thought maybe it was for some other reason – maybe I was dehydrated or my body was fighting off a virus or I was just tired (fatigue is a side effect). But I was eating and drinking enough, sleeping well (if not, more), and had no other odd symptoms going on. I otherwise felt completely healthy.
After ruling out dehydration, COVID (yes, I got tested and an antibody test just in case), and getting my eyes checked out (I thought my vision was worsening, causing the fogginess, but my vision turned out fine), I started to really think this was a medication side effect since there was nothing else to blame it on. I just wasn’t sure initially because dizziness/lightheadedness is not listed in the side effects. However, this medication is very preliminary so there very well could be more side effects that we don’t know about.
At my appointment in early November, it was decided (via the study sponsor protocol) that I needed to hold the drug for some time (we have up to 21 days to do so in this case) to see if I felt better, and if not, potentially rule out the possibility that the medication has been causing this. The study trial has certain levels of severity for side effects to determine if the drug should be held or not. I do not know all of these levels, but I do know that since my lightheadedness was getting in the way of an activity of daily living (driving), the study guidelines are to hold the medication for up to 21 days to see if I feel better or not and then try to go back on it if able to, at a lower dose (this is all based on what I remember being told by my team – I am not versed in the details of the specific study guidelines).
After being off of the drug for 21 days, I didn’t seem to be getting better which made my study doctor think maybe this wasn’t a medication side effect (I actually felt worse towards the end of the hold). So I went back on the medication but at 20mg rather than the 30mg I started at. Of note, my doctor has been very vocal about giving me options – she gave me the opportunity several times to stop the medication if I wanted to, but it was my decision to continue it as I wanted to find out if there was any other way to explain my new symptom. I didn’t want to give up that early.
The same week I restarted my medication, my last attempt to try to explain my lightheaded problem was visiting a vestibular rehab clinic to see if there was something wrong with my inner ear. Lo and behold, after all the testing and ruling out other causes via a brain MRI and head CT (thankfully), it was determined that I have vestibulopathy “of some unknown etiology.” Despite more testing, my vestibular doctor was unable to find a cause for this, but it was not determined that it was the Miransertib. They did state that this phenomenon can happen in individuals my age and oftentimes are unable to find the cause, unfortunately. (I have been managing this through physical therapy and diet modifications).
Is there a tiny chance that this new medication may have irritated a vestibular nerve to cause this? Perhaps. My doctor on the trial thinks it is a small possibility but isn’t positive because this has not been reported in other participants. However, this medication is also still very new so we may not know all of the side effects it could cause. That is one risk we take going on these drug trials – we aren’t really sure what all can happen.
Regardless, I was at least able to remain on the medication. Because of this small setback, I remained on the lower dose of 20mg until my visit in late March, where I went back up to 30mg since I’ve been feeling well (managing my vestibulopathy and not noticing any new side effects/weird changes). So far, after being on the medication since October 2020 (minus the 3 weeks I held it), I have not noticed any change in my lipomatous tissue myself. It’s hard for me to tell any tiny difference since I don’t look at my back every day, but I did start taking my own photos so I can watch for any changes. Thankfully, I haven’t noticed much pain in my upper back recently, where I typically had pain before going on medication.
Anyway, that is where I am now. This is my first time experiencing a clinical drug trial so this is all new to me. It has certainly made me feel a mix of both excitement and anxiety. Excited because this is a new drug that can potentially manage CLOVES! Anxious because what if it doesn’t work out? Or what if it does help, but at the conclusion of the trial, it is not FDA approved so I will no longer be able to access it?
I have had all of these questions floating in my mind and all kinds of feelings about this trial, but in the end, I am just grateful that there is a trial and I am lucky enough to partake in it, whether it works out or not. The simple fact that there are potential treatments out there is exciting enough itself! And I am very grateful for my incredible team.
One thought I’ve been grappling with since the study goals changed and I haven’t noticed any difference after being on Miransertib for 1 year is – do I want to continue this or explore another trial if one opens up? Do I want to start another drug trial all over again? Start a brand new drug with different side effects? It’s a lot to think about.
If anyone reading this is part of a clinical drug trial, I have all the best hopes for you. For anyone thinking about starting a clinical drug trial, I hope that this helped paint somewhat of a picture of what it might be like, though each individual’s experience is different, and each clinical drug trial is different.
This is obviously a big decision for anyone to make based on their own unique situation and not something to take lightly. It’s something to discuss with your medical team and loved ones, so this post sharing my experience is not intended to sway anyone one way or another about deciding to start a trial. The only reason I wanted to share my experience thus far is because I would have wanted the same thing while I was considering this very trial – it is nice to be able to learn about other’s experiences to just gather more information. Hopefully, sharing my experience can help others understand the general experience of a clinical drug trial, think of certain questions to ask their team about the trial they’re considering, or process any feelings that may have surfaced.