Hope this helps, J11:
I have looked on alzforum for the lecanemab article on September 10, though I was unable to find it. Might you supply a url?https://www.alzforum.org/therapeutics/lecanemab
... From what I remember there seemed to be some confusion about the enrollment from China into Clarity. They were continuing to enroll Chinese, even when the trial had apparently completed enrollment?
Haven't seen that, but of the 259 study sites (!) most appear to be in the US, with others in Canada, Australia, China, S. Korea, Japan, Germany, France, Russia (one site) Spain, Singapore, Sweden and the U.K. (Britain only). I assume they are looking to get data on diverse ethnicities and populations so that they can apply to the EU and countries other than the U.S. if the data looks good.
This April 2021 article in Neurology
reports on the participants as of June 2020:
BASELINE CHARACTERISTICS FOR CLARITY-AD: A PHASE 3 PLACEBO-CONTROLLED, DOUBLE-BLIND, PARALLEL-GROUP, 18-MONTH STUDY EVALUATING BAN2401 IN EARLY ALZHEIMER’S DISEASE (3021
As of a data cutoff of June 22, 2020, a total of 801 subjects were enrolled in CLARITY AD. The median age of subjects was 73 years (range: 50–89 years), with 83% of patients 65 years of age or older. Overall, 51% of subjects were female and 78% were Caucasian.
My understanding of the AHEAD trials of lecanemab is that in the US at least, all data is centralized and assessments are recorded for quality and uniformity of administration. Similarly, since CLARITY- AD specifies a positive Amyloid PET scan, with a specific cut-off for "elevated', and specific inclusion criteria, I would assume that the data should be fairly uniform in capture--but then I'm an optimist!...
I am interested in the titration schedule for the phase 3... Basically, patients are at full dose after ~2 months?
Yes; patients are at full dose after 2 months in both Phase 3 AHEAD 3 (intermediate amyloid and normal cognition) and Phase 3 AHEAD 45,(elevated amyloid and normal cognition).
One difference is how often they have to come in: AHEAD 3 participants have monthly infusions (drug or placebo) for the entire 216 weeks of the trial; AHEAD 45 partipants have biweekly (every 2 weeks) infusions for the first 96 weeks, to get the amyloid down fast, and then switch to monthly infusions until week 216. You can see the details in the Arms and Interventions section of the Clinicaltrials.gov: AHEAD3-45 Study
What I only recently realized was that lecanemab could possibly readout much sooner than I had thought...It certainly has me wondering whether at some not distant time in the future the trial could simply be stopped for success....
The CLARITY-AD trial reports this on https://clinicaltrials.gov/ct2/show/NCT03887455?type=Intr&cond=Alzheimer%27s+disease&titles=CLARITY-AD&draw=2&rank=1"
Estimated Primary Completion Date: September 8, 2022
Estimated Study Completion Date : August 29, 2024
Since they are fully enrolled as of about Spring 2021, it's likely that they will need at least a full 2 years to finish the 18-month study and the analyze results. Even "short" studies have enormous data collection and analysis requirements!
Yes, with the 3-45 Phase 3, I can see the logic in moving to the next generation of psychometric tests....What I am unsure about is how much clinical evidence might be expected to demonstrate this? Proving that anti-amyloids stop neurodegeneration at the early stage might take 5-10 years
"Proving" is tricky; having "a pre-determined statistically significant clinical benefit with an appropriate sample size" is assumed in the AHEAD trials, to require about 4 years--since a significant percentage (not a majority) of people with "elevated" amyloid in the AHEAD 45 are expected to show clinical decline over 4 years, even if they do not yet meet the requirement for a diagnosis of MCI or AD. The AHEAD-3 group is far less likely to show clinical decline over 4 years; the Primary outcome there is a change in Amyloid biomarker on PET and the secondary outcome is a change in Tau biomarker on PET. In effect, I assume if CLARITY-AD shows a benefit in those with MCI and AD and AHEAD-45 shows a clinical benefit in those with normal cognition, they would argue that safety and efficacy in removing amyloid and tau is an appropriate "secondary prevention" of clinical decline at the earliest signs of AD biomarkers.
Enough to chew on for now!