A Study of XPro1595 in Patients With Early Alzheimer's Disease With Biomarkers of Inflammation (MINDFuL)

A Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients With Early Alzheimer's Disease With Biomarkers of Inflammation

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.

Study Overview

• Status: Completed
• Conditions: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Alzheimer Disease; Tauopathies; Mild Cognitive Impairment
• Intervention / Treatment: Drug: XPro1595; Drug: Placebo

Detailed Description

This trial is a randomized clinical study using XPro1595 to treat patients with Early Alzheimer's Disease with biomarkers of inflammation (ADi). Early ADi patients are defined as patients with Mild Alzheimer's Disease or Mild Cognitive Impairment (MCI) with a biomarker of inflammation.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • INmune Bio Investigational Site
    • Macquarie Park, New South Wales, Australia, 2113
      • INmune Bio Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5011
      • INmune Bio Investigational Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • INmune Bio Investigational Site
    • Carlton, Victoria, Australia, 3053
      • INmune Bio Investigational Site
    • Ivanhoe, Victoria, Australia, 3079
      • INmune Bio Investigational Site
    • Parkville, Victoria, Australia, 3050
      • INmune Bio Investigational Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • INmune Bio Investigational Site
• Canada
  • Kelowna, Canada, V1Y 1Z9
    • INmune Bio Investigational Site
  • Ottawa, Canada, K1Z 1G3
    • INmune Bio Investigational Site
  • Sherbrooke, Canada, J1L 0H8
    • INmune Bio Investigational Site
  • Toronto, Canada, M3B 2S7
    • INmune Bio Investigational Site
  • Toronto, Canada, M4G 3E8
    • INmune Bio Investigational Site
  • West Vancouver, Canada, V7T 1C5
    • INmune Bio Investigational Site
• Czechia
  • Brno, Czechia, 60200
    • INmune Bio Investigational Site
  • Pilsen, Czechia, 30100
    • INmune Bio Investigational Site
  • Prague, Czechia, 10000
    • INmune Bio Investigational Site
  • Prague, Czechia, 16000
    • INmune Bio Investigational Site
  • Rychnov nad Kněžnou, Czechia, 51601
    • INmune Bio Investigational Site
• France
  • Bron, France, 69500
    • INmune Bio Investigational Site
  • Nantes, France, 44800
    • INmune Bio Investigational Site
  • Toulouse, France, 31059
    • INmune Bio Investigational Site
• Germany
  • Berlin, Germany, 10629
    • INmune Bio Investigational Site
  • Chemnitz, Germany, 09111
    • INmune Bio Investigational Site
• Poland
  • Bialystok, Poland, 15-756
    • INmune Bio Investigational Site
  • Bydgoszcz, Poland, 85-133
    • INmune Bio Investigational Site
  • Wroclaw, Poland, 53-659
    • INmune Bio Investigational Site
• Spain
  • Barcelona, Spain, 08028
    • INmune Bio Investigational Site
  • Barcelona, Spain, 08222
    • INmune Bio Investigational Site
  • Córdoba, Spain, 14004
    • INmune Bio Investigational Site
  • Madrid, Spain, 28006
    • INmune Bio Investigational Site
  • Seville, Spain, 41009
    • INmune Bio Investigational Site
  • Valencia, Spain, 46017
    • INmune Bio Investigational Site
  • Valencia, Spain, 46026
    • INmune Bio Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B16 8LT
    • INmune Bio Investigational Site
  • Bristol, United Kingdom, BS32 4SY
    • INmune Bio Investigational Site
  • Guildford, United Kingdom, GU2 7YD
    • INmune Bio Investigational Site
  • London, United Kingdom, W1G 9JF
    • INmune Bio Investigational Site
  • Motherwell, United Kingdom, ML1 4UF
    • INmune Bio Investigational Site
  • Plymouth, United Kingdom, PL7 8BT
    • INmune Bio Investigational Site
  • Winchester, United Kingdom, S021 1HU
    • INmune Bio Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

The screening window for this trial is 45 days.

Inclusion Criteria:

To be eligible for study entry, patients must satisfy all of the following criteria:

• Adult patients 50 years to ≤ 85 years of age at the time of consent;
• Meets the diagnostic criteria of MCI of probable Alzheimer's disease (Jack et al. 2018; NIA-AA) or mild dementia as clinically described in McKhann, (2011) and corresponding to stages 3 or 4 of the revised AD staging system (Jack, 2018). (NIA-AA);
• Amyloid positive (documented in medical history or assessed during screening through blood test);
• Either currently or previously (in pre-AD condition) literate and capable of reading, writing, and communicating effectively with others;
• Residence in an assisted living is allowed as is personal assistances provided in the home, however at time of enrollment participant must be able to perform most ADL with minimal assistance, and participant must be permitted sufficient independence to allow assessment of change in ADL;
• Has a study partner for the duration of the trial who either lives in the same household or interacts with the patient at least 4 hours per day and on at least 4 days per week, who is knowledgeable about the patient's daytime and night-time behaviors and who can be available to attend all clinic visits in person at which caregiver assessments are performed.

Exclusion Criteria:

Patients will be excluded from the study if 1 or more of the following criteria are applicable:

• Have any contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (e.g., in-skull and cardiac devices other than those approved as safe for use in MRI scanners);
• Receives considerable help to carry out basic ADL living either in the home or as a resident in a nursing home or similar facility;
• Lifetime history of a major psychiatric disorder including schizophrenia and bipolar disorder. Major depressive disorder that has resulted in 2 or more hospitalizations in a lifetime. Major depressive episode during the past 5 years that is judged by the clinical team unlikely to have been part of Alzheimer's prodrome. History of suicidality.
• History of substance abuse within 12 months; use of cannabis or cannabis products within 6 months of consent;
• Enrolled in another clinical trial where patients receive treatment with an investigational drug or treatment device or have had previous treatment with any investigational medicinal product within 60 days or 5 half-lives (whichever is longer) prior to study drug treatment;
• A prior organ or stem cell transplant;
• Seated blood pressure of ≥ 165/105 mmHg at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.0 mg/kg XPro1595; 1.0 mg/kg of XPro1595 will be administered via subcutaneous injection once a week for 23 weeks.	Drug: XPro1595; XPro1595 will be delivered by subcutaneous injection once a week; Other Names: INB03/XPro™; XENP1595; DN-TNF
Placebo Comparator: 1.0 mg/kg Placebo; 1.0 mg/kg of Placebo will be administered via subcutaneous injection once a week for 23 weeks.	Drug: Placebo; Placebo will be delivered by subcutaneous injection once a week; Other Names: Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Early and Mild Alzheimer's Cognitive Composite (EMACC)	Change from Baseline to Week 24 in the Early and Mild Alzheimer's Cognitive Composite (EMACC), a z-score composite of six neuropsychological tests (International Shopping List Test-Immediate Recall; Digit Span Forward/Backward; Category Fluency; Letter Fluency [D-KEFS]; Trail Making Test A and B; Digit Symbol Coding). Each component is standardized to the pooled baseline mean (0) and SD (1), then averaged. Higher scores indicate better cognitive performance; a positive change from baseline indicates improvement.	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CDR-SB	Change from Baseline to Week 24 in the Clinical Dementia Rating - Sum of Boxes (CDR-SB), the sum of the six CDR domain box scores (each 0, 0.5, 1, 2, or 3); total range 0 to 18, with higher scores indicating greater impairment (worse outcome). A negative change favors XPro1595 (less decline).	24 Weeks
Change in Everyday Cognition (E-Cog)	Change from Baseline to Week 24 in the Everyday Cognition (E-Cog) total score, a 39-item informant-report questionnaire that asks the study partner to rate the participant's current performance on cognitively relevant everyday activities relative to 10 years prior (i.e., before illness onset). Activities span memory, language, visuospatial/perceptual abilities, planning, organization, and divided attention. Each item is rated on a 4-point scale from 1 (better or no change) to 4 (consistently much worse). The total score is the mean of all rated items and ranges from 1 to 4, with higher scores indicating greater decline since prior to illness onset.	24 Weeks
Change in Neuropsychiatric Inventory (NPI-12) Total Score at Week 24	Change from Baseline to Week 24 in the Neuropsychiatric Inventory, 12-domain version (NPI-12), a structured interview administered to the study partner (informant) assessing 12 neuropsychiatric domains (delusions; hallucinations; agitation/aggression; depression/dysphoria; anxiety; elation/euphoria; apathy/indifference; disinhibition; irritability/lability; aberrant motor behavior; nighttime behaviors; appetite/eating). Each domain is scored as frequency (1-4) × severity (1-3); the total score is the sum of domain scores and ranges from 0 to 144. Higher scores indicate greater neuropsychiatric burden (worse outcome); a negative change from baseline favors XPro1595. The total score is reported; domain or subfactor scores, where applicable, are interpreted only within the context of the full instrument.	24 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Goal Attainment Scale (GAS)	Goal Attainment Scaling (GAS): an individualized outcome in which each participant set a minimum of three personalized treatment goals at baseline. Attainment of each goal is rated on a 5-point scale (-2 = much worse than expected; -1 = baseline/somewhat worse; 0 = expected goal level; +1 = somewhat better; +2 = much better than expected). A participant's goal ratings are aggregated across goals into a standardized GAS T-score using the Kiresuk-Sherman formula (which accounts for the number of goals and their inter-correlation), scaled to a mean of 50 and a standard deviation of 10. The reported values are the standardized GAS T-score, not the individual -2 to +2 ratings; a T-score of 50 indicates goals were met on average, and higher T-scores indicate greater goal attainment (better outcome).	24 Weeks

Collaborators and Investigators

• Sponsor: Inmune Bio, Inc.
• Investigators: Study Director: Therese Blomberg, INmune Bio

Publications and helpful links

General Publications

• Chance SA, Clover L, Cousijn H, Currah L, Pettingill R, Esiri MM. Microanatomical correlates of cognitive ability and decline: normal ageing, MCI, and Alzheimer's disease. Cereb Cortex. 2011 Aug;21(8):1870-8. doi: 10.1093/cercor/bhq264. Epub 2011 Jan 14.
• Chou RC, Kane M, Ghimire S, Gautam S, Gui J. Treatment for Rheumatoid Arthritis and Risk of Alzheimer's Disease: A Nested Case-Control Analysis. CNS Drugs. 2016 Nov;30(11):1111-1120. doi: 10.1007/s40263-016-0374-z.
• Clark I, Atwood C, Bowen R, Paz-Filho G, Vissel B. Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease links numerous treatment rationales. Pharmacol Rev. 2012 Oct;64(4):1004-26. doi: 10.1124/pr.112.005850. Epub 2012 Sep 10.
• Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006 May 17;295(19):2275-85. doi: 10.1001/jama.295.19.2275.

Helpful Links

• Alzheimer's Association annual report releasing statistics regarding Alzheimer's disease

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Actual): May 12, 2025
• Study Completion (Actual): May 12, 2025

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Biomarker; Inflammation; TNF
• Additional Relevant MeSH Terms: Pathologic Processes; Cognition Disorders; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Alzheimer Disease; Mental Disorders; Inflammation; Dementia; Brain Diseases; Nervous System Diseases; Neurodegenerative Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Tauopathies; XENP 1595
• Other Study ID Numbers: XPro1595-AD-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No