Alba Announces Phase Iia Results

[ENF]

It's looking encouraging, but no date yet on when it will become approved and available.

Open Original Shared Link

[veggienft]

It's looking encouraging, but no date yet on when it will become approved and available.

Open Original Shared Link

Am I reading that wrong, or did the phase 2 trials essentially fail?

If so, it's too bad. I had a lot of hope.

On the other hand, the writeup makes it appear the trial made Alba realize they designed it incorrectly, and that Alba will return with the fix. In other words the phase 2 trial was not fully capable of testing the drug.

..

[elonwy]

Define "fail". It gave them a lot of data to work with. As far as drug release is concerned, it wasn't useful in that way, but considering the difficulty of detecting celiac and the multitude and variety of symptoms possible, I could see where a normal clinical trial would run into difficulty. The drug itself still shows promise though, and I think thats the important part.

[Kathinsearch]

Define "fail". It gave them a lot of data to work with. As far as drug release is concerned, it wasn't useful in that way, but considering the difficulty of detecting celiac and the multitude and variety of symptoms possible, I could see where a normal clinical trial would run into difficulty. The drug itself still shows promise though, and I think thats the important part.

Yes, you are correct.

"Alba's study, the first Phase IIa trial in celiac disease and the first to assess dosing requirements for larazotide acetate, was designed to evaluate the safety, tolerability and efficacy of multiple doses of larazotide acetate in celiac disease subjects during a 2 week gluten challenge. The randomized, double-blind, placebo-controlled clinical trial enrolled 86 patients who had a confirmed biopsy diagnosis for celiac disease and were in compliance with a gluten-free diet for at least six months prior to enrollment as demonstrated by a negative serology test of anti-transglutaminase (tTG). Patients were randomized into seven drug-treated and placebo groups and challenged three times a day with gluten or gluten placebo during a 14 day period. Four doses of the oral formulation of larazotide acetate, all less than 10 mg, were given prior to each gluten challenge. Study endpoints included intestinal permeability (IP), measured as lactulose-mannitol ratio (LAMA), as well as patient signs and symptoms and outcomes, measured by the Gastrointestinal Symptoms Rating Scale (GSRS; validated in several gastrointestinal diseases) and the Psychological General Well-Being Index (PGWBI).

Clinical Findings: * In the primary study outcome, the prevention of increase in LAMA ratio from Day 0 to Day 14, the treatment groups showed a dose dependent protection from increase in intestinal permeability as measured by LAMA ratio versus placebo, however the difference was not statistically significant * In the highest dose active treatment groups of 4 and 8 mg, the LAMA ratio did not increase after gluten exposure when compared with placebo * Post-hoc analysis of change in LAMA ratio from Day 7 to Day 21 showed dose dependent prevention of increase in LAMA across the 4 and 8 mg treatment groups * Changes in PGWBI scores and anti-tTG titers were not significant over the time course of this study * An unexpected enrollment effect resulted in a fall in intestinal permeability from Day 0 to Day 7 across all groups suggesting the need for a run-in period * Larazotide acetate conferred protection from gastrointestinal symptoms as measured by the GSRS as well as from expected signs and symptoms of gluten toxicity * Follow-up studies of longer duration are currently ongoing

Safety: * There was no difference in rate of adverse events between Placebo and Active Drug Groups (46% vs. 55%) * No Serious Adverse Events (SAEs) were reported * Headache was the most common AE (reported by 17/86 subjects), with no differences among the active drug group and the placebo group * Plasma levels of larazotide acetate were below the limits of quantification (0.5 ng/ml) in all groups at days 0, 7 and 14

"Although the primary study outcome was not statistically significant, a great deal was learned about the potential effects of larazotide acetate and the secondary outcome data is very positive. Further, important new information was gained about the best way to run a celiac disease clinical trial. This trial marks the beginning of a new era in celiac therapeutics where modalities beyond diet alone have the ability to improve the lives of our patients," stated Daniel Leffler, MD a gastroenterologist from Beth Israel Deaconess Medical Center.

"We are very encouraged by the clear trend in the reduction of intestinal permeability and the signs and symptoms of gluten exposure in patients with celiac disease. We have applied the knowledge gained in this Phase IIa clinical trial to a larger Phase IIb gluten challenge study which is currently ongoing. In addition, we have recently initiated a clinical trial in 106 active celiac disease patients. Alba is committed to developing and studying new treatment options for patients with celiac disease," stated Dr. Francisco Leon, Head of Clinical Research and Development at Alba. For more information about Alba's clinical trials, please visit the Open Original Shared Link web site and search for Alba Therapeutics."

I'm a lifelong celiac and decided to participate in these trials to help. I am encouraged by this drug! Everyone here who has been gluten-free for at least 6 months should consider participating in the trials, too.

[gfp]

I'm a lifelong celiac and decided to participate in these trials to help. I am encouraged by this drug! Everyone here who has been gluten-free for at least 6 months should consider participating in the trials, too.

Perhaps I misunderstood but they don't seem to want people who have been gluten-free... ???? Don't they require a positive biopsy as part of the trial???

[Darn210]

Perhaps I misunderstood but they don't seem to want people who have been gluten-free... ???? Don't they require a positive biopsy as part of the trial???

My understanding was they wanted Celiacs that were diagnosed through positive biopsy (by their own doctor's) and not through trial/elimination diets.

[Kathinsearch]

Perhaps I misunderstood but they don't seem to want people who have been gluten-free... ???? Don't they require a positive biopsy as part of the trial???

The trial I am on wanted me to document my last biopsy from 1999, which showed recovery from the 1st one done in the 80's. I also brought lab tests showing negative results from different periods of time over the past 10 years. This was to document that I have celiac disease but have recovered. I was lab tested by the researchers and found to be negative for gluten exposure and all other blood tests were fine so I got the Ok to start.

There are others on this trial who recently diagnosed by biopsy, who I believe are now on the diet during the study but I could have misunderstood the researcher on that. There are different parts of the different trials and each have Celiacs required to be on a gluten-free diet 6 months before. I believe the doctors are referring the newly diagnosed patients. I do know that there is a need on the trial for biopsy proven celiac disease'ers gluten-free for 6+ months. I was told last week that now anyone new coming in will have to be biopsied as part of the trial and that I was the last patient not required to do that. My 1999 biopsy came from University of Maryland lab and my doctors were Dr Fasano and Dr Stephen James, who is now head of NIH Digestive Diseases research. The reports discuss my earlier positive biopsy and clinical history and recivery. Pretty clear cut that I have celiac disease. I guess they now want the biopsy done as part of the research in conjunction with the lab tests.

Hope this helps.

[gfp]

The trial I am on wanted me to document my last biopsy from 1999, which showed recovery from the 1st one done in the 80's. I also brought lab tests showing negative results from different periods of time over the past 10 years. This was to document that I have celiac disease but have recovered. I was lab tested by the researchers and found to be negative for gluten exposure and all other blood tests were fine so I got the Ok to start.

There are others on this trial who recently diagnosed by biopsy, who I believe are now on the diet during the study but I could have misunderstood the researcher on that. There are different parts of the different trials and each have Celiacs required to be on a gluten-free diet 6 months before. I believe the doctors are referring the newly diagnosed patients. I do know that there is a need on the trial for biopsy proven celiac disease'ers gluten-free for 6+ months. I was told last week that now anyone new coming in will have to be biopsied as part of the trial and that I was the last patient not required to do that. My 1999 biopsy came from University of Maryland lab and my doctors were Dr Fasano and Dr Stephen James, who is now head of NIH Digestive Diseases research. The reports discuss my earlier positive biopsy and clinical history and recivery. Pretty clear cut that I have celiac disease. I guess they now want the biopsy done as part of the research in conjunction with the lab tests.

Hope this helps.

I'm still trying to work out who is who ....

Isn't Fasano a major shareholder or employed in Alba?

As I understand it the testing will attempt to show that arazotide acetate will allow celiacs to eat small amounts of gluten with minimal damage???

Open Original Shared Link

I would really like to know what share of the estimated $1 billion market Dr. Fasano has.

Is he in for 100 million or just a cool million? Just how independent are the papers he writes and the 'advice' he gives to bodies like the FDA?

I have to to say I find this paper particularly worrying: Open Original Shared Link

At (t-1), the percentage change in Vh/C_D was

9% (95% CI: 3%, 15%) in the placebo group(n=13),

-1% (-18%, 68%) in the 10-mg group (n=13), and

-20% (-22%,-13%) in the 50-mg group (n = 13).

One person had a relapse so serious on 10mg/d that he was removed from the trial.

10mg/day was declared SAFE.... regardless of the results ???? I suppose -1% Vh/C-D is better than -20% ??? but surely +9% is better (or am I just stupid)..

Of course, if you were marketing a drug that would allow people to eat this limit then letting them get sick first then selling them a drug when they no longer can find REAL gluten-free foods is a surefire money winner in the 1 BILLION $/year business?

Lets see where celiac disease research is ????

So from a $325 Million investment no one can find the money to do a clinical trial on the effect of a ZERO GLUTEN DIET on celiacs?

Perhaps they simply don't want to?

Perhaps it is time Dr. Fasano stood one one side of the fence or the other?

Of the 13 people on 10mg/d some had positive villi growth (indeed with so few and an average of -1% it is probable that a few actually gained little) however the of 13 taking the placebo non saw a (whatever Std Dev they used) of +68% ....

How RANDOMLY were these people selected?

How much gluten were everyone in the group already ingesting through CC or mistakes?

How much would it cost to actually do a study where people were actually monitored as to being gluten-free for a good 90 days prior to the trial and blood tests taken before, after 90 days 100% gluten-free and after 90 days on 10mg/d?

To do this the university of Maryland would create some staff study positions or working from home environment.

A NEW kitchen would be built.... only 100% gluten-free would enter the kitchen (raw vegetables, meats, fish etc. and for good measure no dairy or soy). The people on the trial would be allowed to eat ONLY from the kitchen.

Suddenly we have a BASELINE. We can revise the blood tests based on this study... i.e. what is the base for someone NOT eating gluten? How does this differ with different haplotypes (specifically DQ2 and DQ8) ....

[Kathinsearch]

I'm still trying to work out who is who ....

Isn't Fasano a major shareholder or employed in Alba?

As I understand it the testing will attempt to show that arazotide acetate will allow celiacs to eat small amounts of gluten with minimal damage???

Open Original Shared Link

I would really like to know what share of the estimated $1 billion market Dr. Fasano has.

Is he in for 100 million or just a cool million? Just how independent are the papers he writes and the 'advice' he gives to bodies like the FDA?

I have to to say I find this paper particularly worrying: Open Original Shared Link

One person had a relapse so serious on 10mg/d that he was removed from the trial.

10mg/day was declared SAFE.... regardless of the results ???? I suppose -1% Vh/C-D is better than -20% ??? but surely +9% is better (or am I just stupid)..

Of course, if you were marketing a drug that would allow people to eat this limit then letting them get sick first then selling them a drug when they no longer can find REAL gluten-free foods is a surefire money winner in the 1 BILLION $/year business?

Lets see where celiac disease research is ????

So from a $325 Million investment no one can find the money to do a clinical trial on the effect of a ZERO GLUTEN DIET on celiacs?

Perhaps they simply don't want to?

Perhaps it is time Dr. Fasano stood one one side of the fence or the other?

Of the 13 people on 10mg/d some had positive villi growth (indeed with so few and an average of -1% it is probable that a few actually gained little) however the of 13 taking the placebo non saw a (whatever Std Dev they used) of +68% ....

How RANDOMLY were these people selected?

How much gluten were everyone in the group already ingesting through CC or mistakes?

How much would it cost to actually do a study where people were actually monitored as to being gluten-free for a good 90 days prior to the trial and blood tests taken before, after 90 days 100% gluten-free and after 90 days on 10mg/d?

To do this the university of Maryland would create some staff study positions or working from home environment.

A NEW kitchen would be built.... only 100% gluten-free would enter the kitchen (raw vegetables, meats, fish etc. and for good measure no dairy or soy). The people on the trial would be allowed to eat ONLY from the kitchen.

Suddenly we have a BASELINE. We can revise the blood tests based on this study... i.e. what is the base for someone NOT eating gluten? How does this differ with different haplotypes (specifically DQ2 and DQ8) ....

Hey, look, if you have some kind of a beef with all this, why not voice it to Alba and Fasano? I have not seen Fasano since 1999 so I have no clue what you are complaining about. All I know is that I am in the study because I wanted to help in the efforts to get a means for Celiacs to eat gluten or become cured of the disease.

Here is an article by a Celiac who interviewed ALBA in january. She got more of the particulars on what the studies are for and what the outcomes could be. I suggest you read it and contact ALBA and Fasano yourself if you have technical and financial questions instead of spewing drama here that none of us can possibly answer to your liking.

January 16, 2008

A Celiac Pill: Alba Calls for Participants to Test Effectiveness of AT-1001

www.beyondricecakes.com/blog/2008/01/a-celiac-pill-a.html

PS: If Fasano earns money from a patent on a medication that helps Celiacs, then he deserves every cent he gets. Fasano has been a part of Celiac research for the ilatian government for many years and the USA was in the Dark Ages in comparison. He and a few others got Stephens and the NIH to finally look at putting money into real research here in the USA, so to me, he's a hero.

[Kathinsearch]

I'm still trying to work out who is who .... (snip)

By the way, University of Maryland had nothing to do with me getting involved in this study. I found out about the clinical trials in my local newspaper and contacted the in-charge of the trials in Hagerstown, MD, who placed the ad.