Julie G wrote: ↑Wed Dec 28, 2022 7:03 am
Huge thanks to you both for trying to figure this out as it gets to the heart of protecting E4s who participate in the study.
TheresaB wrote: ↑Sun Jan 01, 2023 7:15 pm
More to the story on emphasizing the need to protect us 4s, from this article published in Science on Dec 30, 2022
Revised clinical trial form for Alzheimer’s antibody warned of fatal brain bleeds
Excerpts from the article:
...Taking the antibody alongside blood clot medications, the Japanese biotech company Eisai cautioned, increases the risk of possibly fatal brain hemorrhages....
The question posed in the article about Eisai's communication to trial participants and its transparency about the risks of its product echoes some findings of the Congressional investigation into Biogen and the FDA's approval of aducanumab/aduhelm...
In response to Julie's comment, as a member of the Alzheimer's Clinical Trial Consortium (ACTC) Research Participant Advisory Board, I have asked for specific information about the MRI sequences used in both the CLARITY core study (completed) and its Open-Label Extension (OLE) (ongoing) for people with MCI/Mild AD and for the AHEAD trials (ongoing) in people with normal cognition and intermediate or elevated amyloid. I have been advised that an MD will reply by early next week.
I fully agree with Dr. Karlawish's comment in the article that any approval of lecanemab should carry a black box warning for those taking anticoagulants, and should require both careful monitoring and reporting of events as well as requirements for providers to have experience in administering these drugs for the foreseeable future.
However, I believe that the title itself:
Taking the antibody alongside blood clot medications, the Japanese biotech company Eisai cautioned, increases the risk of possibly fatal brain hemorrhages is evidence of prompt transparency in communication, and is consistent with what I've experienced as a clinical trial participant.
Consent forms are updated as new information is assessed by the outside safety and data monitoring group while the trial is running. Updating consents is a key safety feature for clinical trial participants.
As one such participant, I signed several updated consent forms, each of which was approved by the study site's Institutional Review Board. IRBs act independently, so an updated consent may take weeks to reach each participant, and is shared at an individual visit, not over the phone or by email.
Each time the Nurse Practitioner/Coordinator explained in detail the changes to me, and I indicated that I understood those changes and signed that I consented to continue in the study. I haven't seen the CLARITY consent form, but have been able to see the updated AHEAD consent form, which reflects a lower observed risk of macrohemorrhage at that earlier stage of disease. This isn't a screen shot, but
it is accurate from the June 27, 2022 AHEAD revision. [Note that no deaths have been reported in AHEAD, nor has it been running long enough to have reported more than screening demographics at CTAD] The forum uses this warning graphic on several points, not just macrohemorrhages :
Warning!.png
Cerebral macrohemorrhages and superficial siderosis...Areas of large bleeds in the brain (known as macrohemorrhages) and areas of bleeding on the surface of the brain (known as superficial siderosis) were also seen in participants with AD who were treated with [lecanemab]. They may both be associated with symptoms and may not require treatment. The risk of these types of bleeding abnormalities at the dose and frequency used in this study is low (less than 1 in 100 people).
MRI scans will be done at regular intervals to check for bleeding abnormalities.
If you take medications which prevent blood clots from forming, you may continue with these medications, but you and the study doctor should discuss the risk of bleeding.
We all make our risk assessments of whether a <1% risk is acceptable in anything. The observed risk was 0.6% in those treated with lecanamb and 0.4% in the placebo arm of CLARITY before the OLE, so the provided estimated risk appears to be both accurate and transparent to AHEAD participants.
The FDA has not yet ruled on the request for accelerated approval for lecanemab for MCI/early AD, so I think it's too early to say that it echoes the findings regarding the FDA approval of aducanumab.