GSK1605786 ('786) Drug trial Phase 3

[Mark in Seattle]

Hello,

I have a meeting with my GI next week. He has suggested that I may consider trying a new drug trial run by GlaxoSmithKline. It is a phase 3 trial for a drug they've termed GSK1605786 (referred to commonly as 'GSK786'). I received some literature about it, noting that it was tested on Celiac patients and 50% of them showed short-term liver damage, while with non-Celiac Crohn's patients only 0.5% of them showed the short-term liver damage. Other than that, I don't know much about the drug. As I understand it, there is a 2/3 chance of getting the drug and 1/3 chance of getting placebo.

Here's a link talking briefly about the drug, and here's the relevant text from that link:

GlaxoSmithKline (GSK) and ChemoCentryx, Inc. announced that the first patient with Crohn's disease has initiated treatment in the initial pivotal induction study comparing Traficet-EN, now designated GSK1605786 ('786), to placebo. This marks the start of the Phase III clinical development programme for '786 for the treatment of this serious and chronic disease.
'786 is a non-biologic, orally bioavailable CCR9 antagonist. CCR9 is a chemokine receptor that plays a central role in the inappropriate inflammatory response thought to underlie Crohn's disease. By blocking CCR9, '786 selectively impairs the movement of activated T cells that are involved in causing inflammation of the digestive tract. Its mode of action is believed to reduce inflammation while preserving normal immune function.
The Phase III clinical development programme, that is anticipated to include another pivotal induction study and a pivotal maintenance study, in addition to other studies, will evaluate the efficacy and safety of '786 for inducing a response and remission (reduction or disappearance of symptoms) and maintaining remission in over 2,500 patients with moderately-to-severely active Crohn's disease.
Earlier trial data of '786 for Crohn's disease have been presented at recent congresses including DDW and UEGW, 2010.
Study design
The initial pivotal induction study is a randomised, double-blind, placebo-controlled study that will involve approximately 600 patients to evaluate 500mg of '786 once daily or twice daily compared to placebo in patients with moderately-to-severely active Crohn's disease. The primary and key secondary endpoints are the proportion of subjects achieving a treatment-induced clinical response based on the Crohn's Disease Activity Index (CDAI) and the proportion of subjects achieving clinical remission.

http://medicbest.com/mednews/crohn-s-news/news_2011-07-02-07-08-02-822.html

If anyone has any thoughts, recommendations, suggestions, questions I should consider or ask my doc, I'd appreciate it. I'm kind of leaning toward trying it. Otherwise he's recommending I consider Humira or Remicade.

 

[Shane NZ]

Hey Mark from Seattle

hows your guts doing!

Which drug did you decide to go with? Humira or the Traficet? How did it go? what would you do next time?

I have crohns and have had 3 operations over the last few years and have been on Methotrexate, but that is no longer keeping the crohns at bay. So am looking at which drug to take next.

Any info would be appreciated.

happy eating

Shane Barr NZ

 

[Mark in Seattle]

Hi Shane,

I'm still on prednisone. I did not qualify for the Traficet. I'm hesitant about Humira, just imagining I'll get a bad infection or cancer, etc.

For some reason I'm allergic to AZA & 6mp now.

Humira may be my next option. We'll see. Are you thinking of trying a biologic? Ever tried Aza/6mp?

 

[Shane NZ]

Cheers for your speedy reply Mark

Looks like i qualify for the Traficet at this stage. I had kinda decided on Humira as it appeared to be a bit more "mainstream", it has a lot more data and a longer record than the Traficet or Stelara which is the other trial i was looking at.

But now i am moving more toward Traficet as it looks like it has been developed more with Crohns in mind, and if it doesn't work for me then i can try Humira. Whereas if i try Humira first i don't have time to enroll in the trials as they will be closing here in a few months.

Big decisions! but not really a way to make a sensible decision as i see it - really depends on how each of our bodies handles and responds to the drugs.

Aza/6mp, which we call Azathioprine over here is what my Doc recommends to try after Humira if that doesn't work, but it's real tricky to get as the funding is capped.

Best of luck and sing out if i can help answer any questions you have

 

[Jake Boston]

Hi Mark,

Do you have the information on the GSK'786 and Celiac.

Thanks

 

[Shane NZ]

Hi Mark,

I have decided to go with the Tracficet GSK 786 trial. Start the qualification process on Wed (June 2012).

I have not used Aza/6mp (Azathioprine). Have also tried to stay away from Prednisone, on my Doc's advice. I think cos I have had 3 gut ops and maybe will need more, he seamed to think it would be better if I left the steroids alone.

If the 786 works it will be great (if I get into the trial!) otherwise I will go for the Stelara trial, and failing that i'll go Humira. And then Azathioprine would be my next step - hard for me to get that one where I live.

Still injecting 15mg Methotrexate once per week, and will continue that while on the trials.

Best thing I have done that works is cut down to bare min of food

2-4 Fortisip per day​

1 Scrambled egg​

200g of white fish lightly poached in white sauce​

Boring as but hey you can always spice it up with ... a bit of salt or pepper?

Also 2l of water every day!

Good luck working out whats best for you Mark.

 

[Tenacity]

Hi Mark,

I have decided to go with the Tracficet GSK 786 trial. Start the qualification process on Wed (June 2012).

I have not used Aza/6mp (Azathioprine). Have also tried to stay away from Prednisone, on my Doc's advice. I think cos I have had 3 gut ops and maybe will need more, he seamed to think it would be better if I left the steroids alone.

If the 786 works it will be great (if I get into the trial!) otherwise I will go for the Stelara trial, and failing that i'll go Humira. And then Azathioprine would be my next step - hard for me to get that one where I live.

Still injecting 15mg Methotrexate once per week, and will continue that while on the trials.

Best thing I have done that works is cut down to bare min of food

2-4 Fortisip per day​

1 Scrambled egg​

200g of white fish lightly poached in white sauce​

Boring as but hey you can always spice it up with ... a bit of salt or pepper?

Also 2l of water every day!

Good luck working out whats best for you Mark.

Great I hope it works out for you!

Please keep in touch with us and let us know how you do.

 

[jmcaptain]

Hi:
I have both Crohn's and sarcodosis (both auto-immune diseases). I was on Remicade for two years and Humira for the past three years.

I start testing this week to see if I qualify for the GSK1605786A trial. I am trying to read as much as I can about this trial drug but don't truly have an understanding of what side effects there may be other than the liver involvement for patients with celiac sprue. As I prepare for the drug trial testing, I have had to be off Humira for ten weeks so right now I am on Entocort (see below) and balsalazide disodium.

I did have reactions to both Remicade and to Humira but both worked well for me up until then. My doctor has told me that it matters a great deal what other drugs you have taken before you begin any biologic medicine as to what side effects these drugs might cause -- for example, patients who have been on azipriothine are more apt to have some of the serious side effects like lymphoma.

I have been on prednisone (and still have to take it if I have a flare); I also have been on Entocort, which is a steroid developed specifically for Crohn's -- it doesn't seem to be as immediately effective as prednisone but then again, it doesn't have the nasty side effects either. I also was on methotrexate (in various forms) for several years before I was on Remicade -- it didn't seem to help me much as I would just get sicker and sicker while I was taking it.

I would really like to hear from people who are taking part in the GSK1605786A trial so I know what to expect if I am chosen to participate.
Thanks.
Jackie

 

[Shane NZ]

Hey Jackie,

I have been on the GSK 786 trial for about 2mths now ... but don't know if I'm on Placebo or not! And if on the drug what dosage.

So far my health has stayed the same or maybe a bit worse, so probably worse if you take into account the placebo effect, as in you try something and you are all positive about it which helps your health.

Go ahead with any questions you have and I will do my best to answer them.

Drugs appears to have very little side effects, I have not noticed any, but hey there's a 30% chance I'm on Placebo or low dose. And side effects may not show up for sometime.

Best of luck, and ask away with your questions

Kind regards

Shane

 

[tichard]

Have you started the Clincal Trials?
y

Hi:
I have both Crohn's and sarcodosis (both auto-immune diseases). I was on Remicade for two years and Humira for the past three years.

I start testing this week to see if I qualify for the GSK1605786A trial. I am trying to read as much as I can about this trial drug but don't truly have an understanding of what side effects there may be other than the liver involvement for patients with celiac sprue. As I prepare for the drug trial testing, I have had to be off Humira for ten weeks so right now I am on Entocort (see below) and balsalazide disodium.

I did have reactions to both Remicade and to Humira but both worked well for me up until then. My doctor has told me that it matters a great deal what other drugs you have taken before you begin any biologic medicine as to what side effects these drugs might cause -- for example, patients who have been on azipriothine are more apt to have some of the serious side effects like lymphoma.

I have been on prednisone (and still have to take it if I have a flare); I also have been on Entocort, which is a steroid developed specifically for Crohn's -- it doesn't seem to be as immediately effective as prednisone but then again, it doesn't have the nasty side effects either. I also was on methotrexate (in various forms) for several years before I was on Remicade -- it didn't seem to help me much as I would just get sicker and sicker while I was taking it.

I would really like to hear from people who are taking part in the GSK1605786A trial so I know what to expect if I am chosen to participate.
Thanks.
Jackie

 

[Shane NZ]

Did the initial 3 mths trial which made no difference to my health, good or bad, I felt a bit worse at times as I was meant to be eating a more "normal" diet ... like eating actual food instead of just Fortisip/Ensure! With this 3 month trial we did not know whether I was getting Placebo or low dose or full dose. I sure was hoping it was Plaecbo after the first few weeks as it had no effect!

Now that that 3 mth trial is over and because I did not improve, I have started (on 16 Oct 2012) taking the open label full dosage twice daily. Not counting but I've taken 14 days worth now! No side effects that I'm aware of ... and don't want to get anyone's hopes up (including mine!) but I've only taken 2 Paracetamol since I started these new pills, which considering I was eating them and Tramadol like they were food up till then is hopefully much more than a coincidence.

Guts is still noisy ... but did I mention ... no pain!?

Make no mistake I still feel like I got crohns, tired, weak etc. Nausea seams to have gone though.

Be interesting to see blood results - going in tomorrow. Weight will also be interesting.

As you say side effects are different for everyone, but from where I currently sit I would recommend doing the trial. For me personally I did not find it an emotional roller coaster ... but it does have all the right elements if you're that way inclined! (Crohns goes up and down anyway, the placebo effect - worth a google, pain, testing, wondering etc)

Send me any questions you think I might be able to help with.

Best wishes

Shane

PS I take 15mg Methotrexate weekly/weakly! by injection.

 

[tichard]

Thank you Shane so much for your comments and please keep me updated. My only son who is nine was diagnosed with Crohn's in April of this year. He was doing well until about 9 weeks ago, came down with C-Diff that went into a Crohn's Flare, spent six days in the hosp. He is still weak and having sporadic cramping throughout the day. We started remicade while he was hospitalized. I am determined to be proactive about this disease and not have him live a life on remicade, in and out of hospitals and possible having his organs removed. The doctor already mentioned if the remicade does not work we might have to remove the colon. I am not waiting for that. I am researching all I can and will be trying some in or outside the country

 

[rollinstone]

Any more news on this? Hope you're doing well

 

[Shane NZ]

Yes going good, had no pain relief except a few panadol for occasional headache. Still taking MTX which makes my Wednesdsay! But guts is doing many times better than before I started the 'GSK 786'.

Happy to answer any direct questions, find it hard to answer "Hows it going?!"

But overall if you have crohns I would go check out this pill and see if it's Ok for you.

Best wishes

Shane

 

[rollinstone]

Glad your doing well, have you found out if you were in the placebos or real stuff? I guess my question is what were your Crohn's symptoms before, and what are they now? Glad you're feeling better.

 

[Shane NZ]

Hi Jackie

Crohns symptoms before were pain and weight loss, vomitting, diahorea, I looked green most of the time.
Had a foot of intestine out and some other resections, had a stoma bag for a while, 3 fairly horrific ops really.

Then was on MTX and all was going well after a couple of years after ops. Then the dam crohns started to return, hoped it was just the joins shrinking from the ops at first so had the joins stretched. While they were in there they took biopsies and pics, not good news, active crohns in plenty of places.

Progressively got worse to where I was taking 8 panadol and 8 tramadol a day and still hurting, plus weight loss etc, not much vomitting or diahorea that time as I now have my diet fairly sussed, but often can't eat enough to keep weight on... eat any more though and you get worse ... and then loose weight anyway. Have eaten about 1200 servings of Fortisip - take them real cold and you'll ususally refrain from vomitting!

Now that I'm on the real pills - no pain, no vomitting occasional diahorea (usually self induced from testing new foods)
Still get short on vit b, D, and iron, iron's a pain cos the pills upset my guts and then give me constipation. I eat liqorice for that, but if you eat toooo much .... dolp!

No info available as to what pills I was taking on the first trial, not available till after the trial ends in about 2-3 years. But I think from my biased angle and the blood results - it was placebo.

Once I started taking the pills there was an immediate change, when I forgot my pills on morning I felt I'll that night and thats when I counted all my pills and realised I had missed one dose.

Yes agree, feeling better is great!

Best wishes, you can do it, you can work out what will work best, just keep trying, put off surgery until it's completely necessary

regards Shane

 

[SJF]

It's interesting hear other peoples experience on this trial. My wife has been on it (with 75mg of 6MP daily) since Feb 2012. By May 2012 she was feeling better than she had since she was diagnosed in 2005. Before she started the trial she had several month run with Humira, but stopped due to the horrible side effects.

In January she moved to the open label after she started to feel unwell in December (we suspect she was on full placebo). She's quite sick still, but it did take a while for the '786 to kick in initially.

Her bloods since she started so far indicate the spikes of inflammation moving from full, to half, to placebo through the first part of the trial. So we're hoping in the next few weeks she'll begin to feel good again.

Sam.

 

[Shane NZ]

Good luck, be awesome once she starts feeling better! Make the most of the times when all is going well ... never sure when things turn pear shaped again.

Shane

 

[Moe.]

Seems promising. When is this slated to be on the market. 2016?

 

[Shane NZ]

Hi Moe, where did you hear 2016? or was that a guess?
My GI said his best guess was 2017 so similar time frame. It will depend on side effects and issues they discover from the testing.

So far the only recurring event I have is occasional headache, I used to get these before I started the drug! But the monitors appear interested in it, maybe they are seeing a trend I don't hear about.

Even if headaches are a side effect, I'd rather have a headache once every 10 days or so, than take 16 pills a day for gut pain.

What the longer term side effects are and whether the drug helps avoid recurring surgery are yet to be seen. I was headed back for surgery I guess unless Humira or the likes worked for me. So I'm happy as with GSK786, hope it works for years to come!

Cheers Shane

 

[Mark in Seattle]

Shane, Will they give you the drug as long as you want to take it? Like, will they give it to you for free for the next several years until they launch it?

 

[Shane NZ]

Hey Mark good to hear from you, many thanks for your original help. How you doing? Trying anything thats working or not working?

Nah I only get to take it for 25 months! Dam 3mths gone, not sure what I do after then, had plenty of fairly dodgy ideas from friends and relatives!​

Any ideas welcome. I'll lobby my local guys real hard if all is still going well after 18mths or so. For now I'm just keen to get some life done and then deal with the battle later if it's still working good. I forgot one dose and felt crap within 5hrs, didn't realize until my next dose. So it appears you need to keep taking it. Could have easily been something else that made me feel crap.

I still eat a retricted diet, drink almost nil alcohol, very few fruit or veges, not much bread. Lots of fish, chicken, steak, eggs, 2l water every day, licorice (for constipation as I take iron pills as needed) drink 2-3 fortisip each day, mashed potato from dry powder.​

Back at work, just did a 65 hr week, was a struggle but real cool to do it! Will try to keep it under 40hrs so that I'm not getting too buggered.

Many thanks again for your thoughts all those months ago when there was big decisions to be made and no info!

Best of luck with your guts!​

Kind regards

Shane

 

[Mark in Seattle]

Thanks Shane,

I'm glad it seems to be working well for you. I've been on prednisone for almost 2 years and Humira for about 6 months or so. The prednisone helps with my pain but the Humira does nothing for me. My doctor wants me to have a surgery real soon, stay on Humira, and try to get off prednisone.

I wish I would have qualified for the study for GSK786, as it sounds like some of you on this thread are doing well with it. I hate to have another surgery because this time I have pain in a different location which they haven't been able to get an image of, so I'm just nervous they'll cut too much of my guts out.

Hope it keeps working well. Maybe I can take it in a few years if it passes. Keep us apprised from time to time over the next 2 years if it still works for you.

Mark

 

[tommy1984]

hi guys i have just start the trail for gsk786 on tuesday, so far i havent noticed any signs that im on the full or half dose drug, how long did it take for you to notice and positive signs or syptoms realising it wasnt the placebo? many thanks tom

 

[Shane NZ]

Hi Tommy, when I was on the placebo/Pill trial I stayed sick, so I just kept hoping that I was on the Placebo.
Once I got onto the full dose of the actual pill I started to feel better after about 3 days ... didn't tell anyone as I wasn't real sure if I was just feelin better for a short time! Still feelin much better, keep over doing the work and effort thing though and still get really tired when I take MTX

best of luck

Shane

 

[tommy1984]

Hi shame, thanks for the reply, right ok so I'd guess I'm another unfortunate one then who's got the placebo drug as iv had it for week now but to no joy! Do u suffer a lot with exhaustion mate and mouth ulcers have u managed to pin point weather what types of food may cause this and is there any top tip you recommend, all the best Tom

 

[Shane NZ]

Tommy you may find it better in the long term to be on Placebo in the short term, you are more likely to then be offered open label full dose sooner ... in my dodgy opinion, so be happy!

Fatigue and mouth ulcers, yes and yes. Keep trying stuff and see what works for you, ideally write down some notes as you go otherwise it's real tricky to work out, and remember Crohns comes and goes even if you don't change anything. So it's important to try and retry foods that you think are good and bad.

If I'm feelin extra bad I'll eat white fish poached in milk, I limit my self to under 100grams and thats all I'll eat for that meal, say dinner, then for breakfast I'll have one Fortisip, then 1/2 a plain chicken sandwich for morning tea. You get the picture, eat very little, but regular. If all else fails I'll just have 3 Fortisip a day for a week or so till I feel a bit stable.

If I'm constipated I eat liqorice (try a few brands till you get the one for you - I like the "Black Knight" one) or maybe a few slices of canned peaches and juice.
If I get diarrhea I take an Iron pill.

I drink 2 litres of water almost every day.

I think for me the ulcers and fatique come about when my bowels are extra sluggish and I think I get reflux in my sleep which may promote the ulcers?

I try to eat less but make it as "good" a food as I can think of.

No beer, wine etc DAM!
Really dark chocolate sometimes seams OK.

Top Tip, umm ar well keep trying stuff! Try, try and try again, but don't be a complete idiot if all else fails try something else!
For me KEEP EATING through the good times and the bad ... but eat little and not too often! 5 tiny meals a day till you get a bit better, get bored by having the same things to eat at the same times of day and see how you feel, then once things settle a bit, start testing ONE different thing and see how you feel. Your body needs energy during the rough patches so it's important to keep eating.

Good luck, send me specific questions if you like, about how things go, whats working and whats not.

Try googling "Foods for Crohns" if you haven't already.

 

[Albie]

hi guys,
I also seem to be part of this elite group of GSK1605786A triallers! Have been on it for a week now. No change in symptoms yet (chronic diarrhoea, colic, bloating etc) but feel a bit sick in the gut after the morning dose so have a feeling I've got a least a part dose. Really interesting reading your experiences and will keep track of how you're doing and keep you posted on my progress too!
Cheers

 

[Albie]

hi guys,
I also seem to be part of this elite group of GSK1605786A triallers! Have been on it for a week now. No change in symptoms yet (chronic diarrhoea, colic, bloating etc) but feel a bit sick in the gut after the morning dose so have a feeling I've got a least a part dose. Really interesting reading your experiences and will keep track of how you're doing and keep you posted on my progress too!
Cheers

Ok - just checking back in! Five weeks into the trial, still no real change in symptoms :ymad:

 

[Shane NZ]

Dam! Sad to hear.

What are you eating?

Best wishes

 

[Denis Smith RN]

I am a Research Coordinator for this study. Just wanted to let you guys know that the 12 week trial now has no placebo arm. Participants are randomised to high or low dose. Following this there is a year long study, followed by 2 years open label.

If you are in New Zealand and wish to be considered please get in touch. If you are elsewhere, I can try to get hold of a local contact for you. Good luck.

 

[rollinstone]

any trials across the pond in aus?

 

[Mountaingem]

:hug:Mark, I have no advice, just best wishes, healing thoughts and hugs to send your way! If you are in a serious flare you may want to choose Remicade over Humira, as I didn't get any relief on Humira though YMMV. My doctor said some people just need the infusion over the shot, just something to keep in mind. :hang: