XPro1595 for Alzheimer's Disease

(MINDFuL Trial)

No longer recruiting at 45 trial locations

Overseen By INmune Bio

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Inmune Bio, Inc.

Must not be taking: Cannabis

Disqualifiers: Schizophrenia, Bipolar, Substance abuse, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 24

Duration: 23 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new drug, XPro1595, can improve thinking and daily function in individuals with early Alzheimer's Disease. Researchers will assess the safety and efficacy of this treatment by comparing it to a placebo (a substance with no active medicine). Participants will receive weekly injections for 23 weeks. Suitable candidates have mild cognitive impairment or early-stage Alzheimer's, can perform most daily activities with minimal assistance, and have someone available to assist them regularly. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have used cannabis in the last 6 months or have been in another clinical trial with investigational drugs within 60 days before starting this trial.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

A previous study found XPro1595 to be safe and well-tolerated. Even patients with higher risk factors did not experience major side effects like ARIA-E or ARIA-H, which are types of brain swelling or bleeding. Although scientific journals have not yet published safety data, an independent committee regularly reviewed safety information to ensure participants' well-being. This suggests that XPro1595 appears safe for humans, based on studies conducted so far. ^{1 2 3 4 5}

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

Most treatments for Alzheimer's disease focus on managing symptoms or altering neurotransmitter levels, such as donepezil or memantine. However, XPro1595 works differently by targeting inflammation in the brain, which is thought to be a key factor in the progression of Alzheimer's. This drug specifically inhibits a molecule called tumor necrosis factor (TNF), which is involved in inflammatory processes. Researchers are excited about XPro1595 because this approach could potentially slow down the disease progression rather than just alleviating symptoms, offering a new avenue for treating Alzheimer's effectively.

What evidence suggests that XPro1595 might be an effective treatment for Alzheimer's?

Research shows that XPro1595, a treatment studied in this trial for Alzheimer's Disease, may improve thinking and memory. Earlier studies demonstrated positive effects on mental abilities, mood-related symptoms, and biological signs of the disease. This suggests that reducing inflammation could help manage Alzheimer's symptoms. XPro1595 specifically targets and neutralizes a protein called soluble TNF, involved in inflammation, which might protect brain cells. Early results indicate it could benefit people of different ages and health conditions, offering hope for those with early Alzheimer's. Participants in this trial will receive either XPro1595 or a placebo to evaluate its effectiveness. ^{1 3 4 5 6}

Who Is on the Research Team?

Therese Blomberg

Principal Investigator

INmune Bio

Are You a Good Fit for This Trial?

This trial is for adults aged 60-85 with mild Alzheimer's Disease, confirmed by a biomarker test. Participants must be able to perform daily activities with minimal help and have a caregiver available. Those in other trials, with severe blood pressure issues, MRI contraindications, major psychiatric disorders or recent substance abuse are excluded.

Inclusion Criteria

I can read, write, and communicate effectively.

I am between 50 and 85 years old.

I have been diagnosed with early Alzheimer's disease.

Exclusion Criteria

Seated blood pressure of ≥ 165/105 mmHg at Screening

Have any contraindications to MRI scanning

I need a lot of help with daily activities like eating, dressing, and bathing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1.0 mg/kg XPro1595 or placebo via subcutaneous injection once a week

23 weeks

23 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• XPro1595

Trial Overview The study tests XPro1595 against a placebo in patients with mild Alzheimer's Disease. It aims to assess the drug's impact on cognitive functions and biological markers of inflammation when given as an injection under the skin.

How Is the Trial Designed?

Group I: 1.0 mg/kg XPro1595 Experimental Treatment 1 Intervention

1.0 mg/kg of XPro1595 will be administered via subcutaneous injection once a week for 23 weeks.

Group II: 1.0 mg/kg Placebo Placebo Group 1 Intervention

1.0 mg/kg of Placebo will be administered via subcutaneous injection once a week for 23 weeks.

Who Is Running the Clinical Trial?

Inmune Bio, Inc.

Lead Sponsor

Trials

7

Recruited

340+

Published Research Related to This Trial

In a study involving 8 participants, the use of acute memantine challenges showed promise in predicting individual clinical responses to memantine treatment in Alzheimer's disease.

Participants who were more sensitive to memantine in laboratory tests demonstrated significantly different clinical responses during a 24-week treatment period, suggesting that biomarkers could help tailor memantine therapy for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using Biomarkers to Predict Memantine Effects in Alzheimer's Disease: A Proposal and Proof-Of-Concept Demonstration. Swerdlow, NR., Kotz, JE., Joshi, YB., et al.[2022]

In a 54-week study involving 431 patients with Alzheimer's disease (AD), donepezil significantly delayed functional decline by an average of 5 months compared to placebo.

Patients treated with donepezil had a 38% lower risk of experiencing clinically evident functional loss over the year, indicating its efficacy in preserving daily functioning in AD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Mohs, RC., Doody, RS., Morris, JC., et al.[2022]

AD16, a new drug candidate for Alzheimer's disease, showed a favorable safety and tolerability profile in a study involving 62 healthy Chinese adults, with no serious adverse events reported.

The pharmacokinetics of AD16 indicated that its absorption rate is slowed by high-fat meals, but this does not affect the overall absorption, suggesting it can be effectively administered regardless of meal conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics and effects of diet on AD16, a novel neuroinflammatory inhibitor for Alzheimer's disease: a randomized phase 1 study. Peng, D., Xu, S., Zou, T., et al.[2023]

In a review of 20 randomized controlled trials involving 3049 patients with Alzheimer's Disease, 57.8% of those receiving a placebo reported at least one adverse event (AE), highlighting the significant impact of nocebo effects on treatment adherence.

Approximately 6.6% of patients discontinued placebo treatment due to AEs, indicating that nocebo reactions can adversely affect both patient adherence and the overall effectiveness of treatments in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nocebo in Alzheimer's disease; meta-analysis of placebo-controlled clinical trials. Zis, P., Mitsikostas, DD.[2022]

In a study of 166 patients with moderately severe to severe dementia, memantine treatment resulted in a significant improvement in clinical outcomes, with 73% of patients showing positive responses compared to 45% in the placebo group.

Memantine also led to a notable reduction in care dependence, with an average improvement of 3.1 points on the Behavioral Rating Scale compared to 1.1 points for placebo, indicating its efficacy in enhancing daily functioning without significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Winblad, B., Poritis, N.[2019]

Alzheimer's disease (AD) has many underlying biochemical pathways, making it challenging for single drugs to be effective; however, targeting amnestic mild cognitive impairment (aMCI) may require addressing fewer pathways, potentially allowing for more effective treatments.

Eight drugs have been identified that target various pathways related to both MCI and AD, and combinations of these drugs could offer a promising approach to prevent the progression from aMCI to AD, warranting further clinical trials to test their safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of Alzheimer's disease by treating mild cognitive impairment with combinations chosen from eight available drugs. Fessel, J.[2020]

In a review of 69 Alzheimer's disease clinical trials, study duration was found to be the most consistent predictor of cognitive decline in placebo-treated subjects, indicating that longer trials may lead to more observable changes.

Factors such as the number of investigational sites, frequency of evaluations, and the severity of dementia at baseline were inversely related to cognitive decline, suggesting that these elements should be carefully considered in the design of future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study design factors and patient demographics and their effect on the decline of placebo-treated subjects in randomized clinical trials in Alzheimer's disease. Gold, M.[2022]

In a study involving 183 patients with mild-to-moderate Alzheimer's disease, treatment with dimebon significantly improved cognitive function compared to placebo, as measured by the ADAS-cog scale, with a mean difference of -4.0 points at week 26 (p<0.0001).

Dimebon was found to be safe and well tolerated, with common side effects including dry mouth and depressed mood, but the overall rate of adverse events was similar between the dimebon and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. Doody, RS., Gavrilova, SI., Sano, M., et al.[2016]

In an 11-week study involving 181 patients with mild to moderate Alzheimer's disease, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 did not show significant improvement in cognitive function compared to placebo, as measured by the ADAS-Cog scale.

While there were some marginal improvements in neuropsychiatric symptoms after 8 weeks of treatment, the overall safety profile was similar between LY451395 and placebo, with most adverse events being mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Chappell, AS., Gonzales, C., Williams, J., et al.[2022]

In a phase 2 study involving 353 patients with mild to moderate Alzheimer's disease, the 250 mg dose of ELND005 showed acceptable safety but did not demonstrate significant clinical efficacy compared to placebo after 78 weeks.

While the primary efficacy outcomes were not significant, the treatment did lead to notable changes in biomarkers, such as increased scyllo-inositol levels and decreased Aβx-42 levels in cerebrospinal fluid, suggesting potential mechanisms for further investigation in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Salloway, S., Sperling, R., Keren, R., et al.[2021]

In a study involving 403 patients with mild to moderate Alzheimer's disease, memantine (20 mg/day) showed significant improvements in cognitive function and global status compared to placebo over 24 weeks.

The treatment was generally safe, with a slightly higher rate of discontinuations due to adverse events in the memantine group (9.5%) compared to placebo (5.0%), indicating that while memantine is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. Peskind, ER., Potkin, SG., Pomara, N., et al.[2022]

In a double-blind trial involving 12 patients with probable Alzheimer's disease, treatment with monosialoganglioside (GM1) for 6 weeks did not lead to significant improvements in cognitive test performance.

The study suggests that GM1, which is thought to enhance the effects of nerve growth factor, is not an effective treatment for cognitive decline in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled crossover study of ganglioside GM1 treatment for Alzheimer's disease. Flicker, C., Ferris, SH., Kalkstein, D., et al.[2006]

LY2599666, a monoclonal antibody targeting soluble amyloid-β, demonstrated effective pharmacokinetics and pharmacodynamics in healthy subjects, with a model predicting its ability to suppress Aβ levels in plasma after subcutaneous dosing.

In a small cohort of Alzheimer's patients, the drug was administered weekly for 12 weeks, showing potential for crossing the blood-brain barrier, which is crucial for targeting amyloid-β in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of LY2599666, a PEG-Linked Antigen Binding Fragment that Targets Soluble Monomer Amyloid-β. Li, L., Zhen, EY., Decker, RL., et al.[2020]

In a study involving 30 patients aged 55 to 84 with moderate to severe Alzheimer's disease, memantal (a generic form of memantine) demonstrated moderate positive effects on cognitive functions and daily activities over a 3-month treatment period.

The treatment was found to be safe, with no adverse effects reported, indicating that memantal is both effective and well-tolerated for managing symptoms of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience of the use of memantal in patients with moderate and severe Alzheimer's disease]. Gavrilova, SI., Kolykhalov, IV., Kulik, AS., et al.[2018]

Citations

1. inmunebio.com inmunebio.com/index.php/newsroom/2025-news/muneioeportseyindingsfromhase2urialo20250630043503

INmune Bio Reports Key Findings from Phase 2 MINDFuL ... “Our findings indicate that XPro™ may offer benefits to Alzheimer's patients across all age groups, regardless of comorbidities, additional ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05522387

An Open-Label Extension of XPro1595 in Patients With ... This study is designed as a Phase 2, open label study investigating the safety, tolerability, and efficacy of XPro1595 in patients with Alzheimer's Disease ...

3. medrxiv.org medrxiv.org/content/10.1101/2025.09.24.25336496v1.full-text

XPro1595, a Selective Soluble TNF Neutralizer, in Early ... XPro1595, a Selective Soluble TNF Neutralizer, in Early Alzheimer's Disease with Inflammation (ADi): Results from the Phase 2 MINDFuL Trial.

4. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/XPro1595_UPDATE_%28drug_in_development%29.pdf

XPro1595 Safety and efficacy will be determined when data from clinical trials become available. Neuroprotective Benefit: XPro1595 treatment improved cognitive function ...

5. psychiatrictimes.com psychiatrictimes.com/view/xpro1595-in-early-alzheimer-disease-with-inflammation-phase-2-mindful-trial-results-submitted-for-publication

XPro1595 in Early Alzheimer Disease With Inflammation XPro demonstrated consistent positive trends across cognitive, neuropsychiatric, and biological endpoints, which suggests that targeting ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05318976

NCT05318976 | A Study of XPro1595 in Patients With Early ... The objectives of this study are to determine the safety, tolerability, and efficacy of XPro1595 in patients with early ADi. Detailed Description. This trial is ...