AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

Post by NF52 »

Chicagogirl wrote: Wed Feb 22, 2023 8:47 am...If I have the required Amyloid, my hope is that my brain is healthy enough to go forward with this study. Based on reading all the posting on this drug including the adverse effects and talking to my physicians, I will sign the Informed Consent at VISIT 3
----
This information is based on my understanding of how the trial works. I am a participant, not a medical expert. You should question your Study Coordinator if you apply to be considered for participation in the trial to verify and then review the literature on adverse events with your physician.

Best wishes to all have been following this thread and thanks to those who are participating in this trial. You are all warriors in this quest. I will post more when I know more about my status. Until then.... Remain optimistic!
.
Nevada wrote: Chicagogirl: Great description of your screening for the AHEAD study. I am 2 years into the Ahead-3 arm of the study (visit 24)...
What motivates me to participate is my hope that Lecanemab/Leqembi will be a useful part of treatment for people with beta amyloid risk factors or early signs of dementia. I also feel well cared for by the study staff. I believe that early intervention and additional treatments perhaps in combination will be a key to finding an eventual cure.
Time for full disclosure: I too am in the AHEAD-45 trial, and yesterday received my 32nd infusion of what I believe is lecanemab and not a placebo. More on that in a bit. Chicagogirl and Nevada have known I am in this trial and have respected my decision not to share my participation up to this point. Deep thanks to them both! I hope they will let me intrude just this once on Chicago Girl's forum to share my own experience with lecanemab.

My reason for sharing this now is simple: It's time to demystify participation in clinical trials, especially for those of us who are fortunate to be cognitively healthy while at significantly higher than average risk based on ApoE4 and/or family history. And frankly, if it's okay for someone to share that they have pre-diabetes without having diabetes, or pre-cancerous colon polyps without having colon cancer, or coronary artery disease without a heart attack, it's time to be able to say "I have Preclinical Alzheimer's disease"--a disease that develops for up to 20 years before what we have been conditioned to think of as a specific diagnosis of an already obvious disease called "Alzheimer's" .

Note: Feel free to decide "TL/DR" (too long; didn't read) to the rest of this!

I have both ApoE 4/4 and Preclinical Alzheimer's disease, which I have had since at least 2017, at age 65, although I didn't know it until 2021, two years after the Generations trial ended. If hearing ApoE 4/4 is scary, "Preclinical Alzheimer's disease" is scary on steroids. That why we need to begin to say out loud, without apology: "You can have these disease biomarkers in spite of having done almost everything to prevent them. You still have a fully functioning brain and find joy, purpose and normal, everyday frustrations in your life. And you can decide to act, or not act, on this knowledge with MANY choices"

Blood tests for amyloid are here, and tau blood tests are in clinical trials. MANY people will at some point learn this about themselves--we have to start talking about it now. Preclinical Alzheimer's disease means someone has biomarkers of amyloid beta and/or phosphorylated tau (aka ptau 181 or tau 217) on either blood tests, PET scans or a spinal tap. Since 2005, the ADNI Trials [Alzheimer's Disease Neuroimaging Initiative] has benefited from thousands of volunteers at risk of AD, who agreed to have multiple imaging studies of their brains over time, without knowing the results of those tests and without taking any clinical trial drug. Data also comes from studies of mice with ApoE4 and other risk genes and drug trials in the last decade or so. Amyloid beta plaques (the gravestones of misfolded amyloid beta oligomers) and tau are strongly associated with, but not a certainty for a future diagnosis of Alzheimer's dementia--not vascular dementia, Lewy Body dementia, fronto-temporal dementia, or Parkinson's-related dementia. They are the NOT only road to AD by any means--but for some of us they are like the local interstate-- a fast way to new and unknown destinations.

As with all those other "pre-X" diseases, I have no way of knowing if I have a "use by" date coming up in the next 5 or 20 years. But my risk curve started rising steeply starting about age 65. [7 of the 10 siblings in my mother's family, and all of the 5 sisters, died of Alzheimer's and vascular dementia that started in their early to late 70's; my dad died at age 67 of cardiac arrest after a quadruple bypass.]

I spent many, many hours reading published research, watching presentations by those affiliated and non-affiliated with anti-amyloid research, both pro and con. I take the safety issues as seriously as anyone can take it--because I elected to join the study, putting myself potentially at risk and impacting my husband and family. I have personally discouraged two people with ApoE 4/4 from beginning screening for this trial; one due to severe claustrophobia in an MRI machine, which is required multiple times; the second due to known multiple microhemorrhages and CAA disease, which would almost certainly be disqualifying due to the published results from lecanemab's PHASE 2, CLARITY (CORE) and CLARITY's Open-Label Extension. However, I have seen no reports of deaths in AHEAD in people who all have normal cognition. That MAY mean that further inflammation and damage to blood vessels happens during MCI/mild AD which increases CAA and risk of macrohemorrhage. The final results of AHEAD will not come out until the last-to-join participant finishes their 4 years, probably in 2027 or early 2028.

So here's what being in this trial, and I suspect on lecanemab, has been like for me:
  • After having my weight, BP and temp taken, and my recent medical changes if any updated, my NP Coordinator approves the on-site pharmacist to start making my bespoke dosage of 10mg/kg of weight of either a placebo or lecanemab. No one at the study site knows what I am getting, nor does anyone reading my MRI or PET scan. I am simply getting a number on an IV bag of mostly saline. I settle in for about a 40-45 minute wait, depending on how many other people may also be in line for infusions for this or other trials in other private rooms. The Research Clinic is quiet, unlike any hospital I have ever seen. I joke that it's my spa treatment to sit in a comfy chair, read a great book on my Kindle while drinking coffee or water, listening to a Sirius XM channel of my choice piped in (iPads with Amazon Prime are also available), and have staff who see me every two weeks stop by to share stories of their kindergartner falling asleep on a 10-minute ride home, or their 92 year old dad who loves the family stew recipe, or my own grandkids' latest adventures.
  • I have veins that nurses love, so infusions are a quick jab and an attachment to a long cord that goes to a typical IV stand with the infusion bag that drips slowly into either my left or right arm--usually rotating biweekly. After 60 minutes, the bag beeps, the same nurse returns and adds a quick saline flush for 5 minutes, then removes the needle, puts on a tiny gauze pad and those colorful bandages that wrap around your arm. I read for another 25 minutes, to be sure I haven't had any immediate serious reactions, before they again take my BP, pulse, and temp. Then I head out for an easy hour drive back home. The whole process takes from about 8:50 AM when I leave my driveway to about 1:30 PM when I arrive home.
  • I had "symptoms", or side effects after some of the infusions in the first 7 months without ever feeling like I would have needed to take a day off from doing what I had planned. My symptoms were some of several known side effects, not "adverse events" of lecanemab, in that same way that nausea can be a side effect of antibiotics or feeling wired can be a side effect of prednisone. My side effects have included mild headaches combined sometimes with fatigue that calls out for a nap of an hour or so, and mild nausea and/or abdominal cramps-about what you might get after eating something that you knew you shouldn't. This always happened about an hour or two after waking up, so never interfered with going out later, with the exception of a day early on when I slept for 90 minutes in both morning and afternoon then felt fine.
  • There were also some nights early on with the opposite effect: being wide awake with lists of names, facts or the need to do the NYT crossword puzzle. Not insomnia, more a feeling that my brain seemed to be re-accessing old files. (I now really enjoy the test that starts: "Name words that start with letter ___"!)
  • I also had mild vertigo that was intermittent, never all day/every day. More the sensation of being "still on the boat" I would take one meclizine (the "old" Dramamine) and be fine. Several MRIs during those 6 months showed NO edema, and I was told that the this is a common symptom of lecanemab, but NOT a sign of edema or brain bleeds.
  • At about the 7 month mark, I had a longer episode of about 8 days of intermittent, mild vertigo and mild headache, with no other issues and notified the study site. They promptly cancelled my next infusion and scheduled me for an MRI. That MRI showed one "probable" spot of ARIA-H (Amyloid-Related Imaging Abnormality:micro-hemorrhage) that was less than <5 mm, or slightly less than the diameter of a regular pencil eraser and a dot on an MRI. It was not a stroke and I had no visual, motor, or language effects, nor did my ability to do anything changed. A week or so later I was walking 5 miles on the beach in Maine easily. In the CLARITY trial of people with MCI/mild AD, "isolated ARIA-H", without ARIA- E (edema) was seen in 7.8% of placebo participants and 8.9% of lecanemab participants. In other words, Nevada and I had an almost equal chance of having had a microbleed on either the placebo or on lecanemab.
    I missed one dose, which the Study Site Doctor told the main site would NOT be made up, and have been fine since. Now 14 months in, I have had several more MRIs, all with no signs of ARIA-E or additional microbleeds.
  • I do BETTER now that I did 15 months ago on several tests of "immediate, cued and delayed recall."
    Here's one example: Listen to someone read a list of 12 common grocery store items and then repeat as many as you can in any order. Now the list is repeated; again repeat as many as you can. Repeat two more times. Now remember those words for 20 minutes while your mind is busy on an Ipad task in which you are shown photos of a few dozen people with a name provided for a few seconds. Then you are asked to pick them from photos of people who look similar to them, and then to pick which of three names was theirs, with a first letter cue, if needed. Now repeat the grocery list. That's a test of your hippocampus--and if mine is shrinking from lecanemab, mine appears to have learned how to do more with less.
  • At the end of the calendar year, I got paid $50 for each clinic visit since starting the actual trial, not a huge amount for 5 hours biweekly, or 6 hrs when I have testing, or the MRI or PET scans--also an hour each way. And that money is also taxable, so I on net I get about $ 40. or 8 bucks an hour--not the reason anyone signs up for a clinical trial.
  • At "Week 62/ Visit 37" in AHEAD-speak, I have had a few more infusions more than "Nevada", who is on a monthly schedule with "intermediate amyloid" in AHEAD-3 (defined as 20-<40 centiloids on a PET scan). I am on a biweekly schedule until October 2023, when I too will move to a monthly schedule. My schedule is required to get the elevated (> 40 centiloids) level of amyloid plaques and associated toxic amyloid oligomers removed completely and to reduce both toxic tau and the recently identified toxic "neurofilament light" protein that wreaks havoc in neurons (it's written as Nfl--not NFL football!)
  • My monthly infusions will finish about November 2025. The decision to have a 4-year trial for those of us with normal cognition, versus the 18-month CLARITY trial of lecanemab for those with MCI/mild AD, is due to the different time frames for progression. People can stay at what is called "A+/CN" [Amyloid positive/cognitively normal] for years. Those with a diagnosis usually show slow but measurable change in MCI/mild AD over 18 months.
At about 1/3 through the trial, I feel more alert and have taken on new challenges--like planning a COVID-delayed trip with my husband to two countries with four flights, six cities, trains and buses and lots of great sights to add to my still-working memory.

I have, and always will, respect our absolute right, whether as individuals with normal cognition and risk of AD or as individuals living with cognitive impairments, to follow our values, beliefs and joy. This forum is a wonderful place to put that into action for each of us!

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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

Post by Nevada »

Nancy; Thank you for your eloquent and thoughtful description and discussion of the issues of participating in a clinical trial and especially being "pre-clinical Alzheimers." In this regard, I have been more open with friends and family regarding my risk factors. I have also done public policy volunteer work with the Alzheimer's association for the last 5 years and even recently been interviewed by the local CBS news station. As you indicated, AHEAD is a somewhat unique clinical research trial since its particiants are "healthy functioning" and not (yet) showing clinical signs of dementia. So, we are out there living our lives (perhaps with a little added intensity), traveling, caring for grandchildren, dodging Covid, volunteering, exercising, loving, etc. I work with the study coordinator to schedule appointments within specified "windows" around our active lives since living fully is my first priority. I hope that there will be an open label option at the end of the 4 1/2 year long primary study. In any case, I believe we are gaining useful knowledge about Alzheimer's Disease through such studies and am optimistic that this progress will make a difference in our lifetime. N
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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

Post by Chicagogirl »

NF52 wrote: Fri Feb 24, 2023 6:21 pm Time for full disclosure: I too am in the AHEAD-45 trial, and yesterday received my 37th infusion of what I believe is lecanemab and not a placebo.

My reason for sharing this now is simple: It's time to demystify participation in clinical trials, especially for those of us who are fortunate to be cognitively healthy while at significantly higher than average risk based on ApoE4 and/or family history. And frankly, if it's okay for someone to share that they have pre-diabetes without having diabetes, or pre-cancerous colon polyps without having colon cancer, or coronary artery disease without a heart attack, it's time to be able to say "I have Preclinical Alzheimer's disease"--a disease that develops for up to 20 years before what we have been conditioned to think of as a specific diagnosis of an already obvious disease called "Alzheimer's" .

Nancy
Nancy.... Thanks for your thoughtful and heartfelt description of your participation in this study. Your comment about demystifying participation in clinical trials hit home. I am active in an Adult Recreation Center (those 50 and above) and have told many individuals there that I am screening for the AHEAD trial and why. Their immediate reaction is "You don't have Alzheimer's, do you?". The more I revealed my status the more comfortable I became with it publicly.

I honestly hadn't thought about having Amyloid in the brain is actually considered Pre-clinical Alzheimer's. When I searched on the internet, I found there are actually 3 stages of Pre-clinical Alzheimer's. I imagine I will have this discussion when I receive my Amyloid Pet Scan results in 7-10 days.

Thanks so much for your compassion and insight in all the posts you have responded to. Bravo to you for your most recent post above!!!
;) 4/4 “Choose to be optimistic. It feels better.” Dalai Lama
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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

Post by Julie G »

At about 1/3 through the trial, I feel more alert and have taken on new challenges--like planning a COVID-delayed trip with my husband to two countries with four flights, six cities, trains and buses and lots of great sights to add to my still-working memory.

I have, and always will, respect our absolute right, whether as individuals with normal cognition and risk of AD or as individuals living with cognitive impairments, to follow our values, beliefs and joy. This forum is a wonderful place to put that into action for each of us!
Big hugs, Nancy. Huge thanks for generously sharing your experience. This more than explains your passion around this topic. You, and all of our members, who are participating in the lecanamab trials are very brave and true pioneers. I have great respect and admiration for you and wish you all the best. We are beyond blessed to have you on our team. -xo.
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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

Post by NF52 »

Julie G wrote: Sun Feb 26, 2023 12:31 pm Big hugs, Nancy. Huge thanks for generously sharing your experience. This more than explains your passion around this topic. You, and all of our members, who are participating in the lecanamab trials are very brave and true pioneers. I have great respect and admiration for you and wish you all the best. We are beyond blessed to have you on our team. -xo.
Thank you for your support, Julie. This forum was the first place I found “my people” and it continues to be a place of deep learning and community.
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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

Post by floramaria »

NF52 wrote: Fri Feb 24, 2023 6:21 pm My reason for sharing this now is simple: It's time to demystify participation in clinical trials, especially for those of us who are fortunate to be cognitively healthy while at significantly higher than average risk based on ApoE4 and/or family history.

So here's what being in this trial, and I suspect on lecanemab, has been like for me:
Hi Nancy. Thank you so much for sharing your experience in the lecanemab trial in detail. It is a riveting report and extremely helpful. How exciting that you are doing better on the tests of recall.
Heartfelt thanks to you and the other brave individuals who are moving research forward by participating in clinical trials. We all stand to benefit from your willingness to be part of the clinical trial of Lecanemab.
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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

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Wow! It feels as though the Berlin Wall of Alzheimer's Disease is falling! Not a perfect analogy by far, but my having looked across the bleak Berlin Wall DMZ at machine gunners in towers decades ago from tiny West Berlin comes to mind, inspiring me to be outspoken about my own E4/4 status and my screening blood tests, etc, anticipated at my first AHEAD trial appointment tomorrow. Thank you to brave and brilliant Nancy, as well as to Chicagogirl and Nevada and others who may be either on or considering this path of understanding and ultimately conquering AD. I love this apoe4.info forum community!
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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

Post by Chicagogirl »

Rainy wrote: Mon Feb 27, 2023 4:17 pm Wow! It feels as though the Berlin Wall of Alzheimer's Disease is falling! Not a perfect analogy by far, but my having looked across the bleak Berlin Wall DMZ at machine gunners in towers decades ago from tiny West Berlin comes to mind, inspiring me to be outspoken about my own E4/4 status and my screening blood tests, etc, anticipated at my first AHEAD trial appointment tomorrow. Thank you to brave and brilliant Nancy, as well as to Chicagogirl and Nevada and others who may be either on or considering this path of understanding and ultimately conquering AD. I love this apoe4.info forum community!
Rainy
Thanks so much for your post and your comment about being outspoken about your own E4/4 status. Hope your screening visit went well. I think as more participants post that they are in this trial, the easier it will be for all of us to feel like we are part of something.
;) 4/4 “Choose to be optimistic. It feels better.” Dalai Lama
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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

Post by Chicagogirl »

Interesting posting/video by the University of Penn Memory Center regarding this trial.

https://www.youtube.com/watch?v=Vv365toCTBc
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Re: AHEAD 3-45 STUDY CLINICAL TRIAL (LECANEMAB - BAN 2401)

Post by Chicagogirl »

MY JOURNEY IN THE TRIAL.......

VISIT 3 - (2-3 hours) RESULTS & CONSENT

My visit 3 occurred this week. I was informed (again) that I am APOE e4/e4 Homozygotes (two copies of the e4 gene). I originally learned this when I participated in the Generation's Study Clinical Trial in 2017. This genetic test does not mean you have Alzheimer's. But it is associated with a higher risk of developing Alzheimer's.

Eligibility for the A3 trial requires intermediate amyloid, defined as an Amyloid PET between 20 and 40 Centiloids.

Eligibility for the A45 trial requires elevated amyloid, defined as Amyloid PET over 40 Centiloids. If you are under 20 Centiloids, you are ineligible for the study (a good thing).

Found an explanation of Centiloids: "There has been a creation of a 100-point scale termed "Centiloid", with an average value of zero in "high certainty" amyloid negative subjects and an average of 100 in "typical Alzheimer's patients".

Intermediate or Elevated Amyloid is defined as Preclinical Alzheimer's in RESEARCH studies.

According to the Mayo Clinic:
"There are five stages associated with Alzheimer's disease: preclinical Alzheimer's disease, mild cognitive impairment due to Alzheimer's disease, mild dementia due to Alzheimer's disease, moderate dementia due to Alzheimer's disease and severe dementia due to Alzheimer's disease. Alzheimer's disease begins long before any symptoms become apparent.

This stage is called Preclinical Alzheimer's disease, and it's usually only identified as such in RESEARCH settings. You won't notice symptoms during this stage, nor will those around you.

This stage is also referred to as the "silent stage". By identifying this as preclinical, it identifies those who could have the opportunity for early intervention and treatment. Early intervention is believed to offer the best chance of therapeutic success. There is also diet and lifestyle changes which are discussed throughout this forum.

Since your APOE status doesn't change, I am still APOE e4/e4.

The Amyloid PET Scan said I have ELEVATED amyloid, defined as Amyloid PET over 40 Centiloids. I was hoping to have no amyloid or intermediate levels of amyloid.

Besides the infusions (every 2 weeks or 4 weeks, depending on which arm of the trial you are in) there will be 5 additional visits with your Study Partner over the next 4 years.

Since I have qualified for the AHEAD 45 study I will receive infusions every 2 weeks (dependent on my MRI being clear).

The first step in Visit 3 was further blood work, urine test and the dreaded memory tests (although not as many as the original screening).

I then received the results of my Amyloid PET scan, the APOE genetic test and counseling regarding my status.

I was provided with the consent for participation in the AHEAD-45 study, which must be signed before the baseline visit, which is the first infusion. You do not have to sign at Visit 3. They want you to thoroughly read it, ask any questions and then consent.

NEXT COMES:

VISIT 4 - (2-3 hours) MRI SCAN This scan reviews images of your brain to make sure it is healthy enough to continue in the study.

If approved for the study, after the MRI, you will then have a TAU PET SCAN and then will receive infusions based on which arm of the trial you are on. You will receive either the study drug or a placebo.

VISIT 5 - (2-3 hours) TAU PET SCAN This scans your brain to measure the amount of TAU in your brain using a radiotracer called MK-6240. TAU is second abnormal protein that builds up in the brain of people with Alzheimer's.

This information is based on my understanding on how the trial works. I am a participant, not a medical expert. You should question your Study Coordinator if you apply to be considered for participation in this trial to verify and then review the literature on adverse events with your physician.

Best wishes to all have been following this thread and thanks to those who are participating in this trial. You are warriors in this quest. I will post more when I know more. Until then..... Remain optimistic!
;) 4/4 “Choose to be optimistic. It feels better.” Dalai Lama
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