Prothena ASCENT trial/ PRX012

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Veero
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Prothena ASCENT trial/ PRX012

Post by Veero »

Hi there
I have just signed up days ago for becoming a guinea pig (at a Wellington FL location) and am in the very early stages of getting screened. With luck they won’t find any amyloid in me so there’s a long way to go before I start the drug.

Because I can back out at any time, I figured to check on here on this study in the meantime and any juicy details of good/bad and gossip and so forth on the background of the drug. I did a search on this site and not much came up on it yet. Anyone have any experience hearing from people that are currently in the study receiving it?
Last edited by Veero on Tue Jul 18, 2023 3:16 pm, edited 1 time in total.
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Re: Prothena ASCENT trial/ PRX012

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Veero wrote: Mon Jul 17, 2023 9:13 am Hi there
I have just signed up days ago for becoming a guinea pig (at a Wellington FL location) and am in the very early stages of getting screened. With luck they won’t find any amyloid in me so there’s a long way to go before I start the drug.

Because I can back out at any time, I figured to check on here on this study in the meantime and any juicy details of good/bad and gossip and so forth on the background of the drug. I did a search on this site and not much came up on it yet. Anyone have any experience hearing from people that are currently in the study receiving it?
Hi Veero,

I belatedly noticed your post and want to applaud you for being a "guinea pig"--hopefully treated more like visiting royalty, since clinical trials could not find solutions for diseases without people like you. I wasn't familiar with PRX012, so did some sleuthing. According to the site AlzForum, which is aimed at scientists:
Approximately 50 healthy controls and AD patients will receive a single subcutaneous injection at up to six dose levels, to determine safety, tolerability, immunogenicity, and pharmacokinetics. In April 2023, the company announced they were partnering with a U.S. national drug store chain to accelerate enrollment in an ongoing multiple-ascending-dose study (press release). Top-line data is expected in 2023....Preclinical data showed PRX012 bound Aβ protofibrils with 20-fold higher affinity than lecanemab, and cleared pyroglutamate-modified Aβ42 from brain tissue with three to eight times the potency of donanemab
https://www.alzforum.org/therapeutics/prx012

My layperson translation is that PRX012 is looking to improve the strength of very recent anti-amyloid drugs like donanemb and lecanemab, which are beginning to get FDA approval based on some clinical benefit--but also some risks. One way they are doing that is through a subcutaneous injection, i.e. a shot, probably in your stomach fat, not in your arm like a vaccine. Injections in current studies of other anti-amyloid drugs like donanemab and lecanemab show far lower risks of fluid (edema) or small or large brain bleeds, because the drug reaches your brain at a slower rate, but eventually in the same amount.

In the case of PRX012, they have evidence from mouse studies and other lab work (which is where every human trial starts) that this drug shows a much higher binding to a kind of amyloid beta that is thought to be extra-toxic to our brains, called oligomers and protofibrils. It seems to both prevent them "clumping" into plaques and improves clearing out accumulated plaques.

One of the very novel ways they are seeking people for this early Phase 1 trial of safety and "target engagement, i.e. does the drug do what we think it does in real people, is by partnering with Walgreens to get the word out, especially in areas that may not be near major research centers.
Walgreens and Prothena Partner to Increase Access and Enrollment in Alzheimer’s Disease Clinical Trial

I did notice that the inclusion criteria for this trial includes a clinical diagnosis of Mild Cognitive Impairment or Mild-Stage Alzheimer's, so you will likely have some "fun" cognitive tests as well as those blood tests or PET scan.

Please let us know how it goes. As someone who is currently in the AHEAD-45 trial for people with "elevated amyloid" on a PET scan, the PET scan was a breeze; the MRI was like a NYC construction site and the experience has been one of great support from my trial site.

Nancy
4/4 and still an optimist!
Veero
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Re: Prothena ASCENT trial/ PRX012

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Thanks for taking the time to look into it.
It is apparently given subcutaneously into the upper arm.

I was told that if amyloid on blood was negative/low they would still check it on PET to double check that I didn’t have it there. If I don’t have sufficient amyloid seen on PET then I might be put into a tau medication screening. They also implied that getting the PETs done was the bottleneck in getting patients through the screening process. The local radiology service I guess just doesn’t have bandwidth.

I am not impaired but do have some mild memory lapses but it may just be menopause. My MME was 30 but the test seems so insensitive. I definitely don’t think I qualify for being mid-stage at all and not sure if I qualify for MCI either, so since I immediately got slated into the study I suspect the more subjective qualifiers are less important than more objective radiology results. Either that or they were greedy for my sweet e4e4.
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Re: Prothena ASCENT trial/ PRX012

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Veero wrote: Wed Jul 26, 2023 9:18 pm Thanks for taking the time to look into it.
It is apparently given subcutaneously into the upper arm.

I was told that if amyloid on blood was negative/low they would still check it on PET to double check that I didn’t have it there. If I don’t have sufficient amyloid seen on PET then I might be put into a tau medication screening. They also implied that getting the PETs done was the bottleneck in getting patients through the screening process. The local radiology service I guess just doesn’t have bandwidth.

I am not impaired but do have some mild memory lapses but it may just be menopause. My MME was 30 but the test seems so insensitive. I definitely don’t think I qualify for being mid-stage at all and not sure if I qualify for MCI either, so since I immediately got slated into the study I suspect the more subjective qualifiers are less important than more objective radiology results. Either that or they were greedy for my sweet e4e4.
Thanks for the extra information. I should have read more closely, since they are looking for “healthy controls” also in the quote from AlzForum. You are likely one of those and incredibly important!

I am a “cognitively unimpaired” person with elevated amyloid in the AHEAD prevention of AD trial of lecanemab. (Not always “healthy”since they don’t mind if I have a sinus infection, etc.), but hopefully a phrase I like: “cognitively resilient”.

PET availability is a real issue in screening for clinical trials currently and even more so for recent approval of lecanemab.

The FDA may approve an improved, combined amyloid/tau blood test called PrecivityAD2 this year. You probably had the amyloid-only PrecivityAD test for this trial, which is about 85% accurate in predicting a positive Amyloid PET. Used in a trial with about 500 referrals to memory clinics in Sweden, and combined with APOE4 status, the new version had 95% sensitivity in predicting positive amyloid PET scans. Within a few years or less, PET scans may be used for a few clinical trials, but the blood test may be sufficient for most, and for use with patients considering anti-amyloid therapy who meet the criteria for MCI/mild AD and are not “healthy controls”.
And a shot in the arm sounds much better!!
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Re: Prothena ASCENT trial/ PRX012

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Veero wrote: Mon Jul 17, 2023 9:13 am Hi there
I have just signed up days ago for becoming a guinea pig (at a Wellington FL location) and am in the very early stages of getting screened. With luck they won’t find any amyloid in me so there’s a long way to go before I start the drug.

Because I can back out at any time, I figured to check on here on this study in the meantime and any juicy details of good/bad and gossip and so forth on the background of the drug. I did a search on this site and not much came up on it yet. Anyone have any experience hearing from people that are currently in the study receiving it?
Veero
So nice of you to post your involvement with this trial. I've just started to read about it, and it sounds interesting, especially for those who don't want to go through infusions.

I'm enrolled in the AHEAD 3-45 STUDY clinical trial viewtopic.php?t=8195 and look forward to reading about your journey in yours. Happy Trails!
;) 4/4 “Choose to be optimistic. It feels better.” Dalai Lama
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Re: Prothena ASCENT trial/ PRX012

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For those interested here is their website....

https://ascent-ad.com/
;) 4/4 “Choose to be optimistic. It feels better.” Dalai Lama
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Re: Prothena ASCENT trial/ PRX012

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Has anyone participated this trial?

My mom is currently in it.
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Re: Prothena ASCENT trial/ PRX012

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MasonsMama wrote: Sat May 18, 2024 2:54 pm Has anyone participated this trial?

My mom is currently in it.
Welcome to the forum!

We haven't had anyone posting about being in the Ascent Trial or knowing someone who is, so thank you for being the first. Your mom is one of a fairly small cohort (<100 people) in a Phase 1 trial of PRX012, an injectable ("subcutaneous") anti-amyloid drug made by Prothena, a biotech company based in Dublin, Ireland. ASCENT shows clinical trial sites for what may be an anticipated expansion of their Phase 1 trial at many sites in Florida and a smaller number in other states, but is not currently searchable on clinicaltrials.gov.

I hope you and your mom are finding the experience of being in a clinical trial one that provides information, support, and most important of all, a sense of trust in the study organizers and staff. Anyone participating in a clinical trial is helping to answer crucial questions about how Alzheimer's develops and progresses in people of many different ages and backgrounds. [I'm in the AHEAD-45 trial for people with an elevated amyloid PET scan and no cognitive impairment and am on either lecanemab or a placebo.]

I'm assuming your mom is someone who has been diagnosed with either Mild Cognitive Impairment (MCI) or mild-stage Alzheimer's dementia, which is a requirement for the. Both MCI and mild AD have been the focus of intense interest in anti-amyloid trials, with results suggesting that providing treatment in these early stages may significantly slow changes in functional daily living skills and behaviors and in thinking skills.

PRZ012 may prove to be a very powerful anti-aamyloid drug, if it is both safe and clinically effective, judging from this February 2024 article in AlzForum:
At the April 2023 AD/PD conference in Gothenburg, additional preclinical data showed PRX012 bound Aβ protofibrils with 20-fold higher affinity than lecanemab, and cleared pyroglutamate-modified Aβ42 from brain tissue with three to eight times the potency of donanemab.
https://www.alzforum.org/therapeutics/prx012

In case you're not familiar with the terms researchers use to describe clinical trials in humans (not mice!) here's a helpful section from the National Institutes of Health about Phase 1 and other phases of clinical trials:(NIH)
https://www.nih.gov/health-information/ ... mmon-terms
Phases of Clinical Trials

Clinical trials are conducted in “phases.” The trials at each phase have a different purpose and help researchers answer different questions.

Phase I trials — An experimental drug or treatment in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
Phase II trials — The experimental drug or treatment is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
Phase III trials — The experimental drug or treatment is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments.
Phase IV trials — After a drug is licensed and approved by the FDA researchers track its safety, seeking more information about its risks, benefits, and optimal use.
By definition, a Phase 1 trial is looking to prove a hypothesis that a drug or other intervention is both safe at one or more doses and has a specific pharmacological effect. While Phase 1 studies may also include cognitive or daily living assessments, they typically don't have enough participants to determine clinical effectiveness.

Here's the latest January 2024 Prothena Update
PRX012, a wholly-owned potential best-in-class, next-generation subcutaneous antibody for the treatment of AD that targets a key epitope at the N-terminus of amyloid beta (Aβ) with high binding potency. The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for PRX012 for the treatment of AD.
Encouraging amyloid reduction seen following six months of treatment at 70mg and ARIA-E rate consistent with placebo
Data supports once-monthly subcutaneous treatment and dose escalation in multiple-ascending dose cohorts (200mg and up to 400mg)
Ongoing Phase 1 trial continues as planned and expect to update in 2024
More detailed results on ASCENT may be presented, if available, at either the July Alzheimer's Association conference in Philadelphia or the October CTAD (Clinical Trials of Alzheimer's Disease) conference in Madrid.

In case you are interested in other topics related to ApoE4 and haven't had a chance to browse our forum, I encourage you to check out our Welcome page and the Primer, written by Stavia, a practicing M.D. with ApoE4/4.

The How-To Guide shows how to quote members (use the " icon in the upper right of any post) so they get an email notification of your post. It also shows how to use the Search function for topics, and how to subscribe to topics of interest.

I hope you keep us posted on your mom's participation in the ASCENT trial, and know that she is one of many strong people showing that it is possible to live well, and with purpose with a diagnosis of Alzheimer's disease.

Warmly,
Nancy (Support Team Member)
4/4 and still an optimist!
Veero
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Re: Prothena ASCENT trial/ PRX012

Post by Veero »

It turns out my blood amyloid was positive but the PET was too low for the minimum for the study so they didn’t take me.
[/quote]

Veero
So nice of you to post your involvement with this trial. I've just started to read about it, and it sounds interesting, especially for those who don't want to go through infusions.

I'm enrolled in the AHEAD 3-45 STUDY clinical trial viewtopic.php?t=8195 and look forward to reading about your journey in yours. Happy Trails!
[/quote]
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