Phase 3 Trial Started – Larazotide Acetate

Innovate Pharmaceuticals has started their Phase 3 trial for Larazotide Acetate or INN-202. This is exciting stuff!!

In looking at the clinical trials web site, the trial is available in Topeka, KS, Chesterfield, MI, Concord, NC, and Oklahoma City, OK.

The trial seems to run for 12 weeks with three testing arms – placebo, 0.5mg, and 0.25mg of the drug. The primary endpoint is reduction in CEDPro survey – which is a known survey of celiac related symptoms rated on a scale of 1 to 10. They ask about loose stool, fatigue, headache, etc. They don’t talk about any other end points, gluten challenges, etc.

I have e-mailed and called to try to get more information about this study. I’m still working on it but I wanted to get some of this information out there, so we can get this trial going!!!

Let’s look at bit at the Phase 2b results.

It seems there was a four week placebo run-in to the study. That means people were given placebo for a baseline to establish their symptom pattern. They say, ” ┬áplacebo run-in demonstrated substantial day to day variability in symptoms.” They further say, that, “GI symptoms were reported by more than 90% of patients, and over two-thirds of patients reported tiredness and headache.” So, everyone had GI symptoms and lots and lots had headaches. Larazotide acetate decreased these symptoms by 50% and decreased the anticipated number of days where the patient had abdominal distress by 30 days over 12 weeks. That’s a good decrease.

Because the symptoms varied each day, they can’t determine if this variability was determined by gluten exposure or IBS symptoms or something else. Which is fine, we sometimes feel the same way – eating gluten free sometimes we don’t know what or if anything got us.

Here’s where it gets a little shaky and they recognize the potential limitations of their study. They did not do a gluten challenge in their 2b study, but are comparing these results to previous gluten challenge studies. In doing their gluten challenges, they are basing the results on patient reported symptoms. In one study, 0.25mg and 4mg helped with gluten challenge symptoms while 0.5mg, and 1mg, 4mg, and 8mg did not. In another study, only 1mg helped with gluten challenge symptoms rather than the higher 4mg and 8mg. But it seems they know about this “inverse reaction” and it is common when things are not absorbed well. Inverse reaction is when you take a larger dose of medicine you would expect a bigger result, not smaller. I would have liked to see a single does do better – like the 1mg dose do better in the first study and the second study, but that doesn’t seem to be how this worked.

In the 2b study, the Larazotide Acetate did not increase or decrease the TTG IGA markers in the study participants. However, because there was no gluten challenge there is no way to tell if their drug is protective against damage to the small intestine. Specifically they say, ” efficacy during gluten challenge is suggestive of a mechanism of action relevant to celiac disease, the specificity of larazotide acetate for celiac disease and its utility in other conditions remains to be determined.” Because they are saying that larazotide acetate is a “tight junction” regulator it might be solving symptoms of IBS rather than truly protecting against damage to the small intestine from gluten ingestion.

As I’m reading the study, I found the most telling sentence in the conclusions section of the paper. The sentence says that larazotide acetate may ” represent an important therapeutic option for CeD patients with persistent symptoms although the overall efficacy and risk/benefit ratio of this therapy remain to be fully assessed.” So, the drug may help with symptoms but they are not sure if it actually protects the small intestine from damage with gluten ingestion.

This really begs the question – is a drug that would be taken every day that is not proven to protect the intestines against damage from gluten good enough for Celiac sufferers? In my mind, this needs to be proven a bit more for me to trust it. But that doesn’t mean that it won’t be useful. I just think there needs to be more to this one before I’m willing to seriously think of it as a cure or even something that I’d be interested in looking at.

I want a cure. A cure to me means that I can return to an unrestricted diet. Short of a cure, I want something that protects against cross contamination. Protects against cross contamination means that I still maintain a gluten free diet, but if I go to a friend’s house for dinner I don’t have to worry about whether or not they washed their hands after touching the bread before making my hamburger. Now, this is really the rub – how much is too much cross contamination? Is a crouton okay but a full piece of bread not? I guess that would be different for everyone and that is tricky. Where is the line? Anyway, that debate is for a different post.

Short of cross contamination protection, what would be the point? Symptom protection? My symptoms aren’t that severe, so I’m probably not on board with something just alleviating symptoms. That doesn’t mean this doesn’t have a place. I know that many, many people have severe symptoms from just being in the same room as gluten. This might be a great solution for them. But for me at this point, I want to see more data before I’m convinced.

PS – I have called and emailed about getting into this trial. After a week, I have not received an email response or a return phone call. So, I hope they are truly up and running.

Anyway this has been a long post. I hope it all makes sense. Let me know what you all think.

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