My local JDRF chapter is setting up a "Research Information Committee" to help spread the word about type-1 diabetes research, and I was asked to be a member. We had our first meeting a few days ago, and one of the other members mentioned the following human trial was just getting started:
Xoma Starts a Phase-II Human Trial
Xoma is starting a phase-II clinical trial of their "Xoma 052" drug.
The study is placebo controlled and double blind, and the primary end-point is C-peptide levels (so good design). It is being done in Zurich and I'm not sure how many people will be enrolled. Only people who have had type-1 diabetes for 2 years or longer will be enrolled. So this is not a honeymoon study: quite the opposite; honeymoon diabetics are excluded.
There are already two separate phase-I clinical trials underway to see if Xoma 052 improves type-2 diabetes. (I assume that is why they could go directly to phase-II trials in type-1 diabetes: the basic safety was already established.) Xoma inc. is also doing animal research to see if this drug can be used for many other inflammation related diseases, such as rheumatoid arthritis and gout.
This clinical trial is being funded by JDRF.
Xoma 052 is a monoclonal antibody which is a broad anti-inflammatory, and works by blocking the IL-1 inflammation pathway. Xoma is in the business of developing monoclonal antibodies which are then marketed by much larger companies. They already have a couple of drugs on the market.
Discussion
Earlier this year (and in 2008) there was some excitement about inflammation based treatments as cures for type-1 diabetes. The idea as that the body's autoimmune response triggered inflammation and it was the inflammation which actually killed the beta cells. So lowering inflammation could cure or prevent type-1 diabetes. This is a minority opinion, to be sure. Most researchers believe that inflammation is a side effect of the beta cells being destroyed, not a cause of their destruction. This trial is the third one, that I know of, based on the idea that anti-inflammatories can cure type-1 diabetes.
One of the best things about this research, is that they expect results next year, and as a phase-II trial, it should be big enough, so that the results should be pretty clear as to the basic success of the drug. We should have a basic "thumbs up / thumbs down" result by the end of 2010. Another good thing, from my point of view, is that this is not a honeymoon only treatment or trial.
Personally, I'm a little dubious about the whole "anti-inflammation as a cure" path. But I'm also very data-driven, and we now have 3 different studies going on to try to cure type-1 using this path. If any one of those studies gives successful results, then all my doubts will be erased. :-)
Xoma's press release:
http://www.xoma.com/company/news-events/press-releases/index.cfm?releaseID=421746
Clinical trials record for this research:
http://www.clinicaltrials.gov/ct2/show/NCT00998699
Clinical trials records for Xoma's other diabetes research:
http://www.clinicaltrials.gov/ct2/results?term=xoma+diabetes
Previous blog entry on inflammation (including some general discussion):
http://cureresearch4type1diabetes.blogspot.com/2009/04/two-new-trials-to-test-kineret-anakinra.html
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.
Showing posts with label start. Show all posts
Showing posts with label start. Show all posts
Wednesday, November 18, 2009
Saturday, June 20, 2009
News from MacroGenics on Teplizumab
Two pieces of news from MacroGenics:
First, their phase-II human trial of teplizumab (called PROTEGE) is fully enrolled.
Second, they are starting a follow on phase-III study called PROTEGE ENCORE.
Teplizumab is a "humanized monoclonal antibody" which targets the CD3 part of the immune system in order to lower (or stop) the body's autoimmune response. This drug tries to prevent type-1, or lessen it's severity, by "turning down" the immune system's attack on the body's own pancreas cells. This basic approach has resulted in treatments (but not cures) for other autoimmune diseases. It does carry the risk that the body's immune system will not properly attack a real threat.
Fully enrolling a study (especially one this large: 530 people) is important because the major reason that studies are delayed, is trouble enrolling people in them. Especially a study like this where only "honeymoon" diabetics can participate, getting 530 often takes longer than planned. But once it is fully enrolled, that source of delay is removed.
The new study is a sign that MacroGenics is looking to productize this drug. The new study is focused on "clinical responses". That's research-speak to mean "does it help patients" or "do real people benefit in a useful way from this treatment". This is the kind of trial you do just prior to putting it on the market. The new study is 400 people and is scheduled from June 2009 to June 2012.
There is also a third PROTEGE trial which is ongoing, called PROTEGE Extension, which follows patients from the PROTEGE trial for an extended length of time.
If you view the path to a cure as a race, then with this announcement MacroGenics has pulled even with ToleRx which also has a CD3 targeted humanized monoclonal antibody in phase-III human trials. (That's the DEFEND trial of Otelixizumab.) It is interesting, to me at least, to see the dance of small companies and big companies. The PROTEGE trial is sponsored by MacroGenics. The PROTEGE Extended trial by MacroGenics / Eli Lilly, and the PROTEGE Encore trial by Eli Lilly, so you can see how Eli Lilly taking over the Teplizumab treatment from MacroGenics. Similarly, ToleRx has a partnership with GlaxoSmithKline for their Otelixizumab treatment.
(Note: MacroGenics/Eli Lilly calls PROTEGE a "phase-II/III trial", and the Encore trial a phase-III. But I considered PROTEGE a phase-II and Encore a phase-III.)
You can read more about it here:
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#MacroGenics
(although I really need to update this)
Read the press release here:
http://sev.prnewswire.com/health-care-hospitals/20090616/PH3265516062009-1.html
The web page home of this trial is here:
http://www.protegediabetes.org/
Here are the US Clinical Trial entries for all three studies:
http://www.clinicaltrials.gov/ct2/show/NCT00385697 (Protege)
http://www.clinicaltrials.gov/ct2/show/NCT00870818 (Extension)
http://www.clinicaltrials.gov/ct2/show/NCT00920582 (Encore)
Joshua Levy
First, their phase-II human trial of teplizumab (called PROTEGE) is fully enrolled.
Second, they are starting a follow on phase-III study called PROTEGE ENCORE.
Teplizumab is a "humanized monoclonal antibody" which targets the CD3 part of the immune system in order to lower (or stop) the body's autoimmune response. This drug tries to prevent type-1, or lessen it's severity, by "turning down" the immune system's attack on the body's own pancreas cells. This basic approach has resulted in treatments (but not cures) for other autoimmune diseases. It does carry the risk that the body's immune system will not properly attack a real threat.
Fully enrolling a study (especially one this large: 530 people) is important because the major reason that studies are delayed, is trouble enrolling people in them. Especially a study like this where only "honeymoon" diabetics can participate, getting 530 often takes longer than planned. But once it is fully enrolled, that source of delay is removed.
The new study is a sign that MacroGenics is looking to productize this drug. The new study is focused on "clinical responses". That's research-speak to mean "does it help patients" or "do real people benefit in a useful way from this treatment". This is the kind of trial you do just prior to putting it on the market. The new study is 400 people and is scheduled from June 2009 to June 2012.
There is also a third PROTEGE trial which is ongoing, called PROTEGE Extension, which follows patients from the PROTEGE trial for an extended length of time.
If you view the path to a cure as a race, then with this announcement MacroGenics has pulled even with ToleRx which also has a CD3 targeted humanized monoclonal antibody in phase-III human trials. (That's the DEFEND trial of Otelixizumab.) It is interesting, to me at least, to see the dance of small companies and big companies. The PROTEGE trial is sponsored by MacroGenics. The PROTEGE Extended trial by MacroGenics / Eli Lilly, and the PROTEGE Encore trial by Eli Lilly, so you can see how Eli Lilly taking over the Teplizumab treatment from MacroGenics. Similarly, ToleRx has a partnership with GlaxoSmithKline for their Otelixizumab treatment.
(Note: MacroGenics/Eli Lilly calls PROTEGE a "phase-II/III trial", and the Encore trial a phase-III. But I considered PROTEGE a phase-II and Encore a phase-III.)
You can read more about it here:
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#MacroGenics
(although I really need to update this)
Read the press release here:
http://sev.prnewswire.com/health-care-hospitals/20090616/PH3265516062009-1.html
The web page home of this trial is here:
http://www.protegediabetes.org/
Here are the US Clinical Trial entries for all three studies:
http://www.clinicaltrials.gov/ct2/show/NCT00385697 (Protege)
http://www.clinicaltrials.gov/ct2/show/NCT00870818 (Extension)
http://www.clinicaltrials.gov/ct2/show/NCT00920582 (Encore)
Joshua Levy
Thursday, February 5, 2009
Diamyd Starts Phase-II Trial Aimed at Established Type-1 Diabetics
Diamyd has announced NIDDK is starting a clinical trial to study a combination of their GAD65 immunesupressive together with two drugs designed to stimulate the body's own beta cell growth and insulin generation.
You can read the press release here:
http://www.diamyd.com/docs/PressClip.aspx?PageID=4&ClipID=486
the headline is:
Diamyd's product is an immunesupressive that specifically targets GAD, which is one of the markers for type-1 diabetes. This treatment is currently in two large phase-III trials for honeymoon (recent onset) type-1 diabetics, one in the US and one in the EU. Data from phase-I and phase-II trials, also on honeymooners, show that treated patients use less insulin than untreated patients. Some quite a bit less, and some did not need to use insulin at all for short periods of time. So this is all good news for honeymoon diabetics.
This phase-II human trial takes the same basic treatment and combines it with drugs already approved for type-2 diabetics in an attempt to cure (or improve) non-honeymoon diabetics.
The Study that is Starting Now
They want to enroll 164 people, starting Feburary 2009.
There is no information on how long it will last, or when results will be available.
It is Randomized, Double-Blind, and Placebo Controlled.
One interesting wrinkle is that it is only open to honeymoon diabetics, even thought the treatment is clearly focused on non-honeymooners. I think this is because GAD65 has only been tested on honeymoon diabetics, and is not yet approved for the mass market, so limiting these tests to honeymooners only will speed things along (no extra safety testing for a new population). Anyway the press release makes clear that they are trying to regenerate the body's own ability to make new beta cells (and thus more insulin), and that it is designed for non-honeymooners.
Here is how Diamyd describes it:
This new Phase II study will be the first to combine regenerative agents and Diamyd®. The regenerative agents to be evaluated are lansoprazole and sitagliptin, which are both marketed drugs in the US. The study, to be led by Professor David Harlan at NIDDK, aims to enroll 82 adult patients. "We are excited to start this study to investigate if combining Diamyd® with potentially regenerative stimuli can meaningfully improve treatment of established type 1 diabetes", says Professor Harlan, chief of the Diabetes Branch at NIDDK and professor of medicine at the Uniformed Services University of the Health Sciences.
Notes: NIDDK is part of NIH: the National Institues of Health, part of the federal [USA] government. Also, I think the 82 people listed above is the number who will get the treatment. Another 82 will get placebos, for a total of 164.
You can read more about it at the US Government's Clinical Trials site: http://www.clinicaltrials.gov/ct2/show/NCT00837759
Why is this Important?
In my mind, this clinical trial is very important for two reasons:
First is the tactical reason: Because Diamyd's drug is already undergoing phase-III trials, it could be approved for general use (with a prescription) in 3 or 4 years. The other drugs used in this trial have been generally available for several years. So in just 3 or 4 years we will have results of this phase-II trial and general availability of all the drugs needed. So if this trial is successful, you could actually get the treatment as an "off label" use, if your doctor was willing to write the prescriptions.
Second is the strategic reason: There are several drugs in phase-III and phase-II clinical trials which are targeted at honeymoon type-1 diabetics and which work by stopping the immune attack and "saving" some insulin production. This trial is the first attempt that I know of to take a honeymoon only cure, and make it work on non-honeymooners. But if it works, the same idea could be applied to ToleRx's treatment, Andromedia's treatment, MacroGenic's treatment, Rituximab, Thymoglobulin, Abatacept, etc. That gives us all a lot more chances for a cure using treatments which are already well into the approval process.
Also, one of the controversies in type-1 cure research today is this: does the body naturally regenerate beta cells (and thus insulin production) or not? If the body does, then every honeymoon only cure will become a cure for everyone, if you just wait for the body to regrow it's own beta cells. However if the body does not, then those cures will only work for honeymooners. However, if this clinical trial is successful in finding a path that works with non-honeymooners, then the whole question of regeneration of beta cells is not important: if they naturally regenerate: great. If not, this experiment (if successful) shows how they can be regrown anyway. Type-1 can be cured in either case.
This is big news. This is good news.
You can read the press release here:
http://www.diamyd.com/docs/PressClip.aspx?PageID=4&ClipID=486
the headline is:
DIAMYD® COMBINATION TRIAL AIMED AT REGENERATING INSULIN-PRODUCING CAPACITY IN ESTABLISHED TYPE 1 DIABETES GETS APPROVAL FROM FDA
BackgroundDiamyd's product is an immunesupressive that specifically targets GAD, which is one of the markers for type-1 diabetes. This treatment is currently in two large phase-III trials for honeymoon (recent onset) type-1 diabetics, one in the US and one in the EU. Data from phase-I and phase-II trials, also on honeymooners, show that treated patients use less insulin than untreated patients. Some quite a bit less, and some did not need to use insulin at all for short periods of time. So this is all good news for honeymoon diabetics.
This phase-II human trial takes the same basic treatment and combines it with drugs already approved for type-2 diabetics in an attempt to cure (or improve) non-honeymoon diabetics.
The Study that is Starting Now
They want to enroll 164 people, starting Feburary 2009.
There is no information on how long it will last, or when results will be available.
It is Randomized, Double-Blind, and Placebo Controlled.
One interesting wrinkle is that it is only open to honeymoon diabetics, even thought the treatment is clearly focused on non-honeymooners. I think this is because GAD65 has only been tested on honeymoon diabetics, and is not yet approved for the mass market, so limiting these tests to honeymooners only will speed things along (no extra safety testing for a new population). Anyway the press release makes clear that they are trying to regenerate the body's own ability to make new beta cells (and thus more insulin), and that it is designed for non-honeymooners.
Here is how Diamyd describes it:
This new Phase II study will be the first to combine regenerative agents and Diamyd®. The regenerative agents to be evaluated are lansoprazole and sitagliptin, which are both marketed drugs in the US. The study, to be led by Professor David Harlan at NIDDK, aims to enroll 82 adult patients. "We are excited to start this study to investigate if combining Diamyd® with potentially regenerative stimuli can meaningfully improve treatment of established type 1 diabetes", says Professor Harlan, chief of the Diabetes Branch at NIDDK and professor of medicine at the Uniformed Services University of the Health Sciences.
Notes: NIDDK is part of NIH: the National Institues of Health, part of the federal [USA] government. Also, I think the 82 people listed above is the number who will get the treatment. Another 82 will get placebos, for a total of 164.
You can read more about it at the US Government's Clinical Trials site: http://www.clinicaltrials.gov/ct2/show/NCT00837759
Why is this Important?
In my mind, this clinical trial is very important for two reasons:
First is the tactical reason: Because Diamyd's drug is already undergoing phase-III trials, it could be approved for general use (with a prescription) in 3 or 4 years. The other drugs used in this trial have been generally available for several years. So in just 3 or 4 years we will have results of this phase-II trial and general availability of all the drugs needed. So if this trial is successful, you could actually get the treatment as an "off label" use, if your doctor was willing to write the prescriptions.
Second is the strategic reason: There are several drugs in phase-III and phase-II clinical trials which are targeted at honeymoon type-1 diabetics and which work by stopping the immune attack and "saving" some insulin production. This trial is the first attempt that I know of to take a honeymoon only cure, and make it work on non-honeymooners. But if it works, the same idea could be applied to ToleRx's treatment, Andromedia's treatment, MacroGenic's treatment, Rituximab, Thymoglobulin, Abatacept, etc. That gives us all a lot more chances for a cure using treatments which are already well into the approval process.
Also, one of the controversies in type-1 cure research today is this: does the body naturally regenerate beta cells (and thus insulin production) or not? If the body does, then every honeymoon only cure will become a cure for everyone, if you just wait for the body to regrow it's own beta cells. However if the body does not, then those cures will only work for honeymooners. However, if this clinical trial is successful in finding a path that works with non-honeymooners, then the whole question of regeneration of beta cells is not important: if they naturally regenerate: great. If not, this experiment (if successful) shows how they can be regrown anyway. Type-1 can be cured in either case.
This is big news. This is good news.
Monday, December 1, 2008
New Phase-I Clinical Trial: IL-2 and sirolimus
This trial is open to people diagnosed between 3 months and 4 years ago, so it's not a classic "honeymoon only" study, but it is limited. Patients will be given two drugs over a three month period. The hope is to preserve some beta cells. This is a classic phase-I trial, looking only at safety in a small number of patients.
US Government Clinical Trials Record: http://clinicaltrials.gov/ct2/show/NCT00525889 (NCT00525889)
Immune Tolerance Network Trial Record: http://www.immunetolerance.org/studies/a-phase-i-trial-il-2-and-sirolimus-recent-onset-type-1-diabetes-mellitus (ITN018AI)
Info for patients: http://www.benaroyaresearch.org/files/webfm/diabetes/web_il2_rapa_intervention.doc
General info on Sirolimus: http://en.wikipedia.org/wiki/Rapamycin
General info on IL-2: http://en.wikipedia.org/wiki/Interleukin_2
This study is being done in Seattle Washington, and is sponsored by NIAID.
Joshua
US Government Clinical Trials Record: http://clinicaltrials.gov/ct2/show/NCT00525889 (NCT00525889)
Immune Tolerance Network Trial Record: http://www.immunetolerance.org/studies/a-phase-i-trial-il-2-and-sirolimus-recent-onset-type-1-diabetes-mellitus (ITN018AI)
Info for patients: http://www.benaroyaresearch.org/files/webfm/diabetes/web_il2_rapa_intervention.
General info on Sirolimus: http://en.wikipedia.org/wiki/Rapamycin
General info on IL-2: http://en.wikipedia.org/wiki/Interleukin_2
| Estimated Enrollment: | 10 |
| Study Start Date: | August 2007 |
| Estimated Study Completion Date: | January 2012 |
| Estimated Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
This study is being done in Seattle Washington, and is sponsored by NIAID.
Joshua
Friday, June 6, 2008
New Phase III Trial Starts: Otelixizumab from Tolerx
Good news! A new Phase III trial has started to test a honeymoon cure for type-1 diabetes!
You can read about it (from a technical point of view) here:
DEFEND Trial
Basically, this is a CD3 targeting drug, very similar toTeplizumab by MacroGenics. It is only being tested on honeymoon phase diabetics, but remember my hopeful comments on honeymoon cures becoming cures for everyone. This drug has been in phase II trials for a while, as has Teplizumab.
Press Release Reporting this (see the last paragraph)
You can read about it (from a technical point of view) here:
DEFEND Trial
Basically, this is a CD3 targeting drug, very similar toTeplizumab by MacroGenics. It is only being tested on honeymoon phase diabetics, but remember my hopeful comments on honeymoon cures becoming cures for everyone. This drug has been in phase II trials for a while, as has Teplizumab.
Press Release Reporting this (see the last paragraph)
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