Fingolimod clinical trial update

[shoshin]

Since there was some interest the other day in the Fingolimod (FTY720, an oral pill that they're testing for MS; short overview at http://www.ncbi.nlm.nih.gov/pubmed/18457527) trial that I'm, I thought I'd start a new post. The trial is a phase III trial which means they're testing for the efficacy of the drug (does it actually do what the drug company wants it to; in this case they're primarily measuring number of relapses). Phase II trials are smaller and test mainly for safety. I forgot what phase I is. Anyway, if the phase III works, they'll apply for FDA approval. I get the impression they don't have to wait for this trial to be absolutely finished to apply. According to the paper they gave me, they're trying to enroll 1080 people worldwide in this study so it's pretty big.

I've never done a clinical trial and wasn't even thinking about it until the neuro suggested it.

The trial I'm in is for two years (plus you're supposed to go for a follow-up three months after it's over). There are three arms: 1.25 mg dose, 0.5 mg, or placebo. In some of the earlier trials they used a higher dose than 1.25, but apparently they decided that the 1.25 dose seemed to be working with less side effects so they're trying an even lower dose. I think in some of the other trials they did Fingolimod vs. Avonex, but not both at the same time (so you either got Fingolimod and a fake Avonex shot or Avonex and a sugar pill). You're not allowed to take any of the other DMDs with Fingolimod (I think they're worried about interactions like the way it seemed to turn out that only people who used Tsybari with another DMD got PML (progressive multifocal leukoencephalopathy) and died). I have heard some people have ethical concerns about them having a trial with a true placebo when there are meds that work that they could use instead of a placebo and not totally be withholding treatment. Right now I'm just hoping I got the real thing. Anyway, since 2/3 of the people get the real med, you've got a better shot than in most trials.

There are a lot of tests. According to the clinical coordinator, this is way more than they usually do in trials. Rena, you should go through the screening for this trial--you'd get most of your tests done. I had an eye exam with an OCT (optical coherence tomography) test, a dermatological exam, a pulmonary function test, a brain MRI, a chest HRCT (high resolution computer tomography), an ECG plus I had to wear a Holter-ECG monitor for 24 hours, and various blood and urine tests. There was also a brief neuro exam--I think mostly just to get an EDSS (Expanded Disability Status Scale) score--and some questionnaires. Plus three tests that are part of the MSFC (Multiple Sclerosis Functional Composite)--the speed you can you walk 25 feet in, a test with pegs and hand dexterity, and a crazy math test that you really have to focus on. A lot of these tests are to monitor safety issues (which when the neuro first brought this up with me had all been mild and were reversed when people went off the drug, but it's recently been in the news that two people on Fingolimod died from infection-related causes) and some are to monitor the progress of the disease. Most of the tests are repeated periodically through the trial. I have to go more often for tests right now, but after the three month mark, I'll only have to go every three months (still a lot).

Supposedly, at least on the 1.25 dose, most people get a decrease in pulse rate (about 14 bpm) within a few hours of initially taking the drug. My pulse went down, but not that much, so it's hard to say. When you first take the drug, you have to stay there for six hours so they can monitor your heart rate and blood pressure. So far nothing much has happened, but I'm not actually sure how long it would take to have an effect (I suppose maybe the researchers don't know, either). Wow, this post is getting long, but hopefully it gives you some idea about the whole process.

sho

[Lulu54]

Hi! You may not have noticed, but you posted on a very old thread from 2008.  You might want to copy your comments and post them on a new discussion - many people won't stop and read an old post like this.  

Good luck on the trial - I am excited that they are testing this for PPMS.  We still don't know much about Gilenya (fingoimod) and its use in other types of MS and hopefully the outcomes will be good.  

As for the diet - good for you to make any heath changes that will be positive - we all probably could do with less fat.  
best, Lulu


PS if you feel lonely, come back and hang out.  The place gets slow o n the weekends but really moves Monday - Friday.

[motherg7]

So glad to read your post!  I was diagnosed with PPMS in April and was lucky enough to get into the trial with fingolimod.  Started taking the drug/placebo August 10th.  I am convinced I'm on the 'real' drug.  I've also gone on a modified Swank MS diet of ultra low fat especially saturated fat.  Was eager to start physio, but broke my foot August 25th.  Obviously need to concentrate on balance.  I am regularly overwhelmed by how this has changed everything in my life.  The feelings of uselessness, guilt, idleness, frustration.  I guess I'm just glad to hear from someone who also has PPMS and is in the trial.  Less lonely somehow.  Thanks!

[shoshin]

Thanks for the supportive comments. It's good to know I'm not the only one with a little cognitive dissonance over these MS categories.

I don't think I'm going to get rid of my nagging doubts, but I guess the drug company has already spent a ton of money on the screening so I might as well stick it out and see if there's any effect.

sho

[essdipity]

You're doing the right thing. Not to worry about ethical considerations. You've been up front with your neuro about all your symptoms, including when they started and stopped (or didn't stop), to the best of your ability and memory. That's all you can do.

I believe he is right about categories of MS. Many just don't fit into that tight box. My own neuro still considers me to be RRMS, despite the fact that this last whatever has been non-stop since last September. Yet he says RR is the best fit. I'm leaving it at that and I hope you will too. Sometimes we plateau at a certain level of symptoms and that becomes a new baseline. Crappy but true.

I think you're a brave soul to do the trials. It's a relief to know that F. has been through all the parts to see if it is dangerous (we hope), yet still there's no final outcome. It's people like you who help the rest of us, and I thank you. Please let us know how everything goes on a frequent basis.

ess

[shoshin]

I changed my image to a pic of fingolimod in case anyone would like to see what it looks like. It's not a large pill.

Penn: Glad you found it interesting. There's so much MS research, it's hard to know what to try to keep up with, but this at least seems promising to turn into something useful in the near future.

Quix: Well, you managed to hit my ethical Achilles heel with your question.

There are a bunch of qualifications to be in the study. Some of them have to do with not having too advanced of MS and not having confounding health issues. For example, I had to be able to walk 500 meters (a little less than a third of a mile) unaided and have an EDSS (Expanded Disability Status Scale, see http://ms.about.com/od/multiplesclerosis101/a/ms_edss.htm) score of less than 5.5.

You also have to have been off any other DMD for at least three months. Not a problem for me since I have never been on one.

And you are supposed to have RRMS and have had a relapse within the past year. This is where it gets dicey. When I was dx'd I was convinced I had PPMS. My neuro thinks I have RRMS. I am still not sure if he knows something I don't know, he's just not paying enough attention, or I'm not a clear-cut case (the first time I saw him he said not everyone falls neatly into those boxes).

The first time I saw the MS neuro, he said since I had had symptoms for a long time (ten years) and they were still mild (he seemed to think this had some predictive power) and since I didn't have prominent, acute relapses or inflammation, he wasn't sure how much the DMDs would help me. Since I stubbornly (stupidly?) don't like taking medicine, this played into what I wanted to hear. At that time I was pretty stable and I figured I could live with things the way they were. Maybe I would work on diet and lifestyle issues.

When I went for my follow-up appt in March, the neuro started talking to me about this trial and asked when my last relapse was. I was stumped so he gave up.

However, I had been starting to feel worse shortly before the appointment and then had also come down with a bad cold. I told him that if it kept going like this maybe I did want to start a DMD in the future. He said if I thought I wanted to try a DMD I should do it now, since the earlier you take them, the more effective they are. So I walked out of that appt signed up for Copaxone.

I got home and thought, "What have I done?" The next day my legs felt decidedly worse and the whole trial idea kind of nagged at me. So I emailed the neuro and asked if this could be a relapse. I figured maybe I just hadn't noticed the relapses before when I thought I had peripheral neuropathy because I wasn't looking for them and they were never dramatic, acute changes.

We went round about this a bit, but the neuro said a relapse doesn't have to be some major thing--it's relative and people's experiences vary. So I asked if I could still get in the trial (that carrot of possible neural repair dangling in front of me) and he said yes.  

However, I guess I keep waiting for the remission to prove that this really is a relapse. It's been a little more than three months now and in fact, the way I feel is that I am getting a little bit worse each day. I'm not sure that's how a relapse is supposed to work. So now I'm not really sure if this really is a relapse or if it's actually some kind of slow decline.

I told the neuro I am having more trouble walking, etc., but he doesn't seem too concerned. I didn't really pursue it since as far as I can tell, he can't do anything about it anyway.

But I do feel a little bit like maybe I don't quite belong in this trial and I've gotten in under false pretenses. And I hope that since I'm just one little data point among many, I won't mess anything up too much.

On the other hand, if I really do have PPMS, I selfishly figure I'm better off with a 67% chance at something of unknown efficacy than 100% chance at something that probably won't work.

Sorry, this was probably a lot longer answer than you wanted, but this is a bit of sore point for me.

sho

[Quixotic1]

This was really, really interesting.  I'm so proud of you doing it!  And thank you for the in-depth view into the process.

What category of MS are they recruiting?  I am presuming RRMS, but, do they say?

And the trial is for a decent amount of time.  These studies that go one only for 4 months don't give a whole lot of information.

Fingers crossed that you are in the 2/3!!

Thanks!  Quix

[pennst8r]

Thanks for the info. I am not diagnosed, nor necessarily convinced my issue is MS. However, both of my sisters have MS, so I plan to pass the info on to them.

There is a woman in my agency w/ MS who has been in some clinical trials for her MS doc, who is reportedly quite reknown (spelling?) in the field. I do not see her often, as her office is not in or near my building. I will be seeing her on Tuesday for a meeting, so I may mention it to her as well.

Thanks again. Good luck with your trial!

Penn