XPro1595 for Alzheimer's Disease

(MINDFuL Trial)

Recruiting at 39 trial locations

Overseen By INmune Bio

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Inmune Bio, Inc.

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The goal of this Phase 2 Alzheimer's study is to determine whether 1.0 mg/kg XPro1595 confers a benefit on cognition, function, and biomarkers of white matter and to further evaluate safety and tolerability. The objectives of this study are to determine the safety, tolerability, and efficacy of XPro1595 in patients with early ADi.

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.

What data supports the idea that XPro1595 for Alzheimer's Disease is an effective drug?

The available research does not provide any data supporting the effectiveness of XPro1595 for Alzheimer's Disease. The studies mentioned focus on other treatments like ganglioside GM1, dimebon, LY2599666, and memantine, but none of these studies include XPro1595. Therefore, there is no evidence from the provided information to suggest that XPro1595 is an effective treatment for Alzheimer's Disease. ^{1 2 3 4 5}

What safety data is available for XPro1595 in Alzheimer's treatment?

The provided research does not contain specific safety data for XPro1595, Pegipanermin, or XPro in the treatment of Alzheimer's disease. The studies mentioned focus on other treatments such as ELND005 and memantine. ^{5 6 7 8 9}

Is XPro1595 a promising drug for Alzheimer's Disease?

The information provided does not directly address the effectiveness of XPro1595 for Alzheimer's Disease. The articles focus on other drugs and treatments, so we can't determine if XPro1595 is promising based on this data. ^{10 11 12 13 14}

Research Team

Therese Blomberg

Principal Investigator

INmune Bio

Eligibility Criteria

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

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

Have any contraindications to MRI scanning

Treatment Details

Interventions

• Placebo ()
• XPro1595 (Anti-inflammatory)

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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 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]

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]

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 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]

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 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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled crossover study of ganglioside GM1 treatment for Alzheimer's disease. [2006]

3. England 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. [2016]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of LY2599666, a PEG-Linked Antigen Binding Fragment that Targets Soluble Monomer Amyloid-β. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. [2021]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinical experience of the use of memantal in patients with moderate and severe Alzheimer's disease]. [2018]

8. England 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). [2019]

9. United States pubmed.ncbi.nlm.nih.gov

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

10. England 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. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Nocebo in Alzheimer's disease; meta-analysis of placebo-controlled clinical trials. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. [2022]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Using Biomarkers to Predict Memantine Effects in Alzheimer's Disease: A Proposal and Proof-Of-Concept Demonstration. [2022]