PMN310 for Alzheimer's Disease

Recruiting at 21 trial locations

Overseen By Wendy Luca

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ProMis Neurosciences, Inc

Must be taking: Acetylcholinesterase inhibitors, Memantine

Must not be taking: Anti-amyloid treatments

Disqualifiers: Parkinson's, Huntington's, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 12

Duration: 48 weeks

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of PMN310, an experimental drug for individuals in the early stages of Alzheimer's disease. Participants will receive either PMN310 or a placebo through an IV infusion to observe the drug's effects on their condition. The trial seeks individuals with mild memory issues due to Alzheimer's who are not residing in a long-term care facility. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial allows patients to continue taking FDA-approved acetylcholinesterase inhibitors or memantine as long as the dose has been stable for at least 3 months before screening. However, if you are currently receiving anti-amyloid treatments, you must stop them at least 9 months before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that PMN310 is generally well-tolerated. In earlier studies, patients received monthly doses of PMN310, which reached effective levels in the body without causing major problems. Unlike some treatments that target amyloid plaque and raise safety concerns, PMN310 focuses on harmful proteins called toxic amyloid-beta oligomers, which are linked to Alzheimer's, to avoid these issues.

Animal studies have tested the treatment, and it successfully protected against the harmful effects of these proteins. While this is encouraging, these studies are still early steps in understanding PMN310's safety for humans. As this is a Phase 1 trial, the main goal is to learn more about its safety and how the body processes the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Most treatments for Alzheimer's disease, like donepezil and memantine, focus on managing symptoms rather than targeting the underlying cause. PMN310 is unique because it targets toxic amyloid-beta oligomers, which are believed to play a key role in the progression of Alzheimer's. Researchers are excited because PMN310's specificity could potentially slow down or halt the disease process, offering more than just symptomatic relief. This approach could represent a significant advancement in treating Alzheimer's by addressing the root of the problem.

What evidence suggests that PMN310 might be an effective treatment for Alzheimer's?

Research has shown that PMN310 is a promising treatment for Alzheimer's disease. It targets the harmful forms of amyloid-beta, a protein linked to Alzheimer's, without affecting the harmless forms. This approach could reduce harmful effects while avoiding unnecessary interactions. Early studies showed positive results regarding the drug's safety and patient tolerance. The U.S. FDA has given PMN310 a Fast Track designation, recognizing its potential to meet the urgent need for better Alzheimer's treatments. These findings suggest that PMN310 could effectively treat Alzheimer's by focusing on the most harmful proteins involved in the disease. Participants in this trial will receive one of three dosages of PMN310 or a placebo, administered as a 60-minute infusion. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with early Alzheimer's disease. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a particular stage or severity of Alzheimer's.

Inclusion Criteria

I am 50 or older and can see and hear well enough to do tests.

Patient and caregiver provide written informed consent

I've been on a stable dose of medication for Alzheimer's for at least 3 months.

Exclusion Criteria

Pregnant or breastfeeding

Living in a continuous care or long-term care nursing facility

Negative PET scan with any amyloid-targeting ligand within 6 months of Screening or during Screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PMN310 or placebo once every 28 days for a total of 12 infusions

48 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PMN310

Trial Overview The study is testing PMN310, which is given through IV infusions to see if it's safe and can help patients with early Alzheimer's. It will also compare results against a placebo group that receives no active drug.

How Is the Trial Designed?

Group I: Cohort 3 PMN310 1400 mg or placebo Experimental Treatment 2 Interventions

PMN310 1400 mg or placebo administered as a 60-minute infusion.

Group II: Cohort 2 PMN310 700 mg or placebo Experimental Treatment 2 Interventions

PMN310 700 mg or placebo administered as a 60-minute infusion.

Group III: Cohort 1 PMN310 350 mg or placebo Experimental Treatment 2 Interventions

PMN310 350 mg or placebo administered as a 60-minute infusion.

Who Is Running the Clinical Trial?

ProMis Neurosciences, Inc

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

Tacrolimus (FK506), an FDA-approved calcineurin inhibitor, can be safely delivered to APP/PS1 mice using time-release pellets, leading to normalization of calcineurin activity and significant reduction of Alzheimer's disease (AD) pathologies such as synapse loss and neuroinflammation.

The treatment with FK506 not only alleviated cognitive impairment and neuroinflammation but also preserved normal immune responses, suggesting it could be a promising early intervention for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term normalization of calcineurin activity in model mice rescues Pin1 and attenuates Alzheimer's phenotypes without blocking peripheral T cell IL-2 response. Stallings, NR., O'Neal, MA., Hu, J., et al.[2023]

In a 24-week open-label extension study involving 175 patients previously treated with placebo, those who switched to memantine showed significant improvements in functional, global, and cognitive assessments compared to their decline while on placebo.

The safety profile of memantine remained favorable, with a high completion rate of 78%, reinforcing its efficacy and safety for treating moderate to severe Alzheimer disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease. Reisberg, B., Doody, R., Stöffler, A., et al.[2022]

In a preliminary study of 16 patients with early Alzheimer's disease, the p38α kinase inhibitor neflamapimod showed potential to improve episodic memory function, with significant increases in memory scores observed at 28 and 84 days.

While there were no overall group effects on brain amyloid plaque load, a responder analysis indicated that some patients experienced a reduction in amyloid signal, suggesting a possible impact on β-amyloid production that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An exploratory clinical study of p38α kinase inhibition in Alzheimer's disease. Scheltens, P., Prins, N., Lammertsma, A., et al.[2022]

APP-C31, a peptide produced from the cleavage of amyloid precursor protein, enhances the aggregation and toxicity of amyloid-β40 (Aβ40) peptides, which are implicated in Alzheimer's disease pathology.

The study reveals that APP-C31 promotes the formation of large Aβ40 deposits in neurons, leading to increased cell damage and apoptosis, suggesting it could be a novel target for Alzheimer's disease treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APP-C31: An Intracellular Promoter of Both Metal-Free and Metal-Bound Amyloid-β40 Aggregation and Toxicity in Alzheimer's Disease. Nam, E., Lin, Y., Park, J., et al.[2023]

The study identified a novel PSEN1 variant (p.E318G) that is significantly associated with high levels of tau and phosphorylated tau in cerebrospinal fluid, indicating its potential role as a biomarker for Alzheimer's disease (AD).

Individuals carrying the p.E318G variant, especially those with the APOE-ε4 allele, face a significantly increased risk of developing AD, with a risk level comparable to that of APOE-ε4 homozygous individuals, highlighting the variant's importance in AD susceptibility and progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PSEN1, p.E318G variant increases the risk of Alzheimer's disease in APOE-ε4 carriers. Benitez, BA., Karch, CM., Cai, Y., et al.[2022]

In a study involving 41 Alzheimer disease patients, acupuncture alone showed a significant improvement in cognitive function (measured by MMSE) compared to a combination of acupuncture and music therapy.

While both treatments improved patient outcomes, acupuncture alone was found to be more effective than the combination therapy, suggesting that acupuncture may be a stronger intervention for enhancing therapeutic effects in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation on acupuncture combined with music for treatment of Alzheimer disease]. Liu, G., Yuan, LX.[2018]

Despite over 50 drug candidates passing phase II trials for Alzheimer's disease, none have successfully completed phase III trials, highlighting the challenges in developing effective treatments.

Current trends in Alzheimer's drug discovery include the development of disease-modifying agents that aim to slow disease progression, multitargeted drugs addressing multiple pathways, and the repositioning of existing medications for new therapeutic uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugs in Clinical Trials for Alzheimer's Disease: The Major Trends. Bachurin, SO., Bovina, EV., Ustyugov, AA.[2018]

Aβ1-40 oligomers stimulate the production of interleukin-6 (IL-6) in human microglial cells, indicating a link between amyloid beta accumulation and neuroinflammation in Alzheimer's disease.

The activation of p38 MAPK is crucial for the increase in IL-6 secretion, suggesting that targeting this pathway could be a potential therapeutic strategy to reduce neuroinflammation associated with Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

p38 MAPK Is a Major Regulator of Amyloid Beta-Induced IL-6 Expression in Human Microglia. Lin, H., Dixon, SG., Hu, W., et al.[2023]

Inhibiting microglial p38α in a mouse model of Alzheimer's disease did not lead to changes in behavior, inflammation levels, or overall amyloid plaque burden, suggesting that targeting this pathway may not have harmful effects in early-stage Alzheimer's.

The study found that while microglial p38α inhibition altered microglia-plaque interactions, it increased levels of soluble Aβ42, indicating a complex role of p38α in neuroinflammatory responses that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early chronic suppression of microglial p38α in a model of Alzheimer's disease does not significantly alter amyloid-associated neuropathology. Braun, DJ., Frazier, HN., Davis, VA., et al.[2023]

Citations

1. promisneurosciences.com promisneurosciences.com/news-media/press-releases/detail/246/promis-neurosciences-granted-fast-track-designation-by-u-s

ProMIS Neurosciences Granted Fast Track Designation by ... FDA designation highlights the potential of PMN310 to deliver a more targeted approach to treating Alzheimer's Disease.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06750432

PMN310 in Patients With Early Alzheimer's Disease ... This Phase 1b study aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of multiple IV infusions of PMN310 ...

3. neurologyadvisor.com neurologyadvisor.com/news/non-plaque-binding-therapy-fast-tracked-for-alzheimer-disease/

Non-Plaque Binding Therapy Fast Tracked for Alzheimer ... ProMIS Neurosciences presents positive data from PMN310 phase 1a clinical trial at the 17th Clinical Trials on Alzheimer's Disease Conference.

4. promisneurosciences.com promisneurosciences.com/news-media/press-releases/detail/251/promis-neurosciences-announces-second-quarter-2025

ProMIS Neurosciences Announces Second Quarter 2025 ... “In addition, our recent FDA Fast Track designation for PMN310 underscores the urgent need for safer, more effective Alzheimer's treatments.

5. biospace.com biospace.com/press-releases/promis-neurosciences-receives-dsmb-approval-to-advance-to-final-dose-escalation-cohort-in-phase-1b-alzheimers-trial-of-pmn310

ProMIS Neurosciences Receives DSMB Approval to ... The study has been designed with a sample size intended to provide sufficient power to provide meaningful insight into effects of PMN310 on ...

6. promisneurosciences.com promisneurosciences.com/news-media/press-releases/detail/252/promis-neurosciences-receives-dsmb-approval-to-advance-to

Press Releases “Unlike therapies directed at amyloid plaque, which continue to be associated with safety concerns, PMN310 is engineered to avoid plaque and ...

7. promisneurosciences.com promisneurosciences.com/news-media/press-releases/detail/232/promis-neurosciences-presents-positive-data-from-pmn310

Press Releases Results indicated PMN310 was generally well-tolerated and monthly dosing can provide CSF levels adequate for target engagement Initiation…

8. neurology.org neurology.org/doi/10.1212/WNL.0000000000204094

Protection against toxic amyloid-beta oligomers by ... The antibody PMN310 was shown to selectively bind toxic AßO and protect against their pathogenic activity in vitro. In two rodent models of AD, PMN310 protected ...

9. firstwordpharma.com firstwordpharma.com/story/5982670

ProMIS Neurosciences Granted Fast Track Designation by ... The ongoing PRECISE-AD Phase 1b trial is evaluating PMN310 in patients with early AD. The study is focused on characterizing safety, ...