blp wrote:Hi folks. I completed screening for Generations 1 and began taking either CNP520 50 mg or Placebo just this week... One of the changes they pointed out to me that is that they are considering lowering the CNP520 dose from 50 mg per day to 50 mg per week or 6 mg per day. From the wording in the consent form this seems to be related to a review of the data done by the "(unblinded) Data Monitoring Committee (DMC)"... Does anyone else know more about this possible change to the Generations 1 protocol?
Welcome, blp!
I am also in the Generations 1 Study and have been for about 21 months. I still remember the feeling of accomplishment to finally have the "baseline day" arrive and go home with those 4 bottles of pills (whether they were CNP 520 or a placebo!) I think close to 10 people overall on the forum are in either the Generations 1 or Generations 2 study, and some more people have gone through some of the screening process.
As for your new consent, I probably will get a similar update in 3 weeks when I go for my next short appointment, but had heard some rumors about a possible change in dosage at some future point. While I can't tell you what the study researchers have planned yet, I have some ideas.
First, any change in consent has to be approved by each cooperating institution's (i.e. university or research center) Institutional Review Board, a process that can take months. I have probably signed 3 or 4 new consent forms since I started the screening process in January 2017, and know that the site I am on took months to approve adding CNP520 to the original CAD106 immunotherapy arm. So that stage of the process is one that places the health and informed consent of participants front and center.
Second: The way it was explained to me is that every large drug trial like this has an outside committee of people not affiliated with either the study sites, the drug company or anyone directly involved in working with the participants. They are the only ones during the trial who periodically look at "unblinded" data (the real results of people on the trial, using participant study numbers, not names). This is done at certain points to be sure that the drug is not causing any serious adverse events (SAEs) that would require the trial to be cancelled. This happened last fall with some other BACE-1 inhibitor trials using a different formulation than CNP520, when they discovered that some people during the first year on those two drugs had some abnormal liver enzyme results. After those trials were cancelled, the CNP520 Data Monitoring Committee did an unblinded review in January 2019 to check for any similar effects. They did not find any, but added additional first year monitoring for an extra level of scrutiny. I heard from my nurse practitioner that a later analysis also failed to find any harmful effects from CNP520.
Data monitoring groups can also look to see if drugs are showing enough difference from the placebo to justify continuing what are expensive, years-long trials. The other arm of Generations 1, using CAD106, started about a year earlier than CNP520 and went through that analysis last year (called a "futility analysis" since if a drug is half-way through its trial and shows no difference than a placebo it may be "futile" to continue.) It passed, by the way, so people on that "arm" of Generations 1 are now in their 2nd or 3rd year in some cases.
What I suspect might be a possible outcome of the Data Monitoring is that they have discovered that participants on CNP520 show the expected 80% or higher reduction of amyloid beta in the brain, since that is what was found on an earlier Stage 2 13-week trial using 2mg, 10 mg, 35mg. and 80 mg. dose formulations of CNP520l. People on the 2 mg. daily dose showed a 20-30% reduction in amyloid beta and on the 35 mg dose showed an average of about 62% reduction of amyloid beta.
https://www.novctrd.com/CtrdWeb/displaypdf.nov?trialresultid=15947
One option, that I have heard proposed, is that if anti-amyloid treatments are successful, they would be used in the future with an initial higher dose to greatly reduce the existing amyloid beta in the brain, and then reduced to a "maintenance" dose to keep production of toxic amyloid at a low level, while allowing other functions of the Amyloid Precursor Protein (APP) which the BACE-1 drug inhibits, to function at a higher level. (Full disclosure--this is third-hand information and probably Novartis and Generations 1 researchers would groan if they read my explanation.)
So think of it this way: they are keeping their options open to reduce the amount of CNP520 in your system, probably because they are still working out approvals for how and when they would do that. If I hear more in three weeks, I'll post an update (or send you a Private Message.) In the meantime, I want to thank you for being willing to have lots of blood drawn, lie still through those noisy MRIs and the much quieter PET scans, and take all those lovely tests (which confirm for me exactly what I have always known are my strengths and weaknesses!) I hope your study partner is as happy for you and patient with his/her time commitment as my husband.
If you want to find some easy ways to navigate this site, quote other users, and search for topics of interest, check out
"How-To" Get the most out of the ApoE4.info website
You have lots of good company on this forum, both in study participants and in those who know what a brand new world awaits when you discover your ApoE 4 status. Hugs from a friend in Virginia!
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