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: Recruiting
• 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 with a biomarker of inflammation.

• Study Type: Interventional
• Enrollment (Estimated): 201
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: INmune Bio; Phone Number: (858)964-3720; Email: trials@inmunebio.com

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Completed
      • INmune Bio Investigational Site
    • Macquarie Park, New South Wales, Australia, 2113
      • Recruiting
      • INmune Bio Investigational Site
      • Contact: INmune Bio, Inc.
  • South Australia
    • Adelaide, South Australia, Australia, 5011
      • Recruiting
      • INmune Bio Investigational Site
      • Contact: INmune Bio, Inc.
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Recruiting
      • INmune Bio Investigational Site
      • Contact: INmune Bio, Inc.
    • Carlton, Victoria, Australia, 3053
      • Recruiting
      • INmune Bio Investigational Site
      • Contact: INmune Bio, Inc.
    • Ivanhoe, Victoria, Australia, 3079
      • Recruiting
      • INmune Bio Investigational Site
      • Contact: INmune Bio, Inc.
    • Parkville, Victoria, Australia, 3050
      • Recruiting
      • INmune Bio Investigational Site
      • Contact: INmune Bio, Inc.
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Recruiting
      • INmune Bio Investigational Site
      • Contact: INmune Bio, Inc.
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Z 1G3
      • Not yet recruiting
      • INmune Bio Investigational Site
      • Contact: INmune Bio, Inc.
    • Toronto, Ontario, Canada, M4G 3E8
      • Not yet recruiting
      • INmune Bio Investigational Site
      • Contact: INmune Bio, Inc.
• Poland
  • Białystok, Poland, 15-756
    • Recruiting
    • INmune Bio Investigational Site
    • Contact: INmune Bio, Inc
• United Kingdom
  • Birmingham, United Kingdom, B16 8LT
    • Recruiting
    • INmune Bio Investigational Site
    • Contact: INmune Bio, Inc
  • Bristol, United Kingdom, BS32 4SY
    • Recruiting
    • INmune Bio Investigational Site
    • Contact: INmune Bio, Inc.
  • Guildford, United Kingdom, GU2 7YD
    • Recruiting
    • INmune Bio Investigational Site
    • Contact: INmune Bio, Inc.
  • London, United Kingdom, W1G 9JF
    • Recruiting
    • INmune Bio Investigational Site
    • Contact: INmune Bio, Inc.
  • Motherwell, United Kingdom, ML1 4UF
    • Recruiting
    • INmune Bio Investigational Site
    • Contact: INmune Bio, Inc
  • Plymouth, United Kingdom, PL7 8BT
    • Recruiting
    • INmune Bio Investigational Site
    • Contact: INmune Bio, Inc.
  • Winchester, United Kingdom, S021 1HU
    • Recruiting
    • INmune Bio Investigational Site
    • Contact: INmune Bio, Inc.

Participation Criteria

Eligibility Criteria

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

Description

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; NIAAA) or mild dementia as clinically described in McKhann, (2011) and corresponding to stages 3 or 4 of the revised AD staging system (Jack, 2018);
• 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 received treatment on another AD clinical trial within the last 60 days from Day 1;
• 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 in the Early and Mild Alzheimer's cognitive composite (EMACC) from Baseline to Week 24 in the following assessments: International Shopping List Test-Immediate recall (Word List learning Test); Digit Span Forward and Backward; Category Fluency Test (DKEFS); Letter Fluency Test (DKEFS); Trail Making Test Parts A and B; Digit Symbol Coding Test To assess the efficacy of XPro1595 compared with placebo on cognitive performance in patients with mild AD	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who experience adverse events and serious adverse events	Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram findings and other safety assessments will be recorded as adverse events if the findings meet the defined criteria for adverse events.	Baseline up to 28 days post last dose
Change in Clinical Dementia Rating (CDR)	Change from Baseline to Week 24 in Clinical Dementia Rating Scale (CDR) The CDR scale is a clinician-rated dementia staging system that tracks the progression of cognitive impairment in 6 categories (memory, orientation, judgement, and problem solving, community affairs, home and hobbies, and personal care). Each category is scored on a 5-point scale in which None = 0, Questionable = 0.5, Mild = 1, Moderate = 2, and Severe = 3. The global CDR score is established by clinical scoring rules and has values of 0 (no dementia), 0.5, (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is obtained by adding the ratings in each of the 6 categories and ranges from 0 to 18 with higher scores indicative of greater impairment. To assess the effect of XPro1595 compared with placebo on cognition and global function in patients with mild AD	24 Weeks
Change in apparent fiber density (AFD)	Change from Baseline to Week 24 in apparent fiber density (AFD) To assess the efficacy of XPro1595 compared with placebo on axonal integrity in patients with mild AD	24 Weeks
Change in Everyday Cognition (E-Cog)	Change from Baseline to Week 24 in Everyday Cognition (E-Cog) To evaluate the effect of XPro1595 compared with placebo on E-Cog	24 Weeks
Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)	Change from Baseline to Week 24 in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) To assess the effect of XPro1595 compared with placebo on ADL in patients with mild AD.	24 Weeks
Change in myelin content	Change from Baseline to Week 24 in free-water-corrected tissue Radial diffusivity and 1 of the following i) MRI-specific myelin contrast: ii) a magnetization transfer ratio (MTR) iii) an inhomogeneous magnetization transfer (MT) or iv) an myelin water fraction (MWF) map To assess the efficacy of XPro1595 compared with placebo on myelin in patients with mild AD.	24 Weeks
Change in non-cognitive behavioral symptoms	Change from Baseline to Week 24 in (Neuropsychiatric Inventory [NPI] caregiver items) To assess the effect of XPro1595 compared with placebo on noncognitive behavioral symptoms in patients with mild AD	24 Weeks
Change in gray matter integrity	Change from Baseline to Week 24 in Cortical Disarray Measurement (CDM®) To assess the efficacy of XPro1595 compared with placebo on gray matter integrity in patients with mild AD	24 Weeks
Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid)	Number of participants with a reduction in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration amyloid) from Baseline to Week 24. To assess the efficacy of XPro1595 compared with placebo on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid).	24 Weeks
Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)	Change from Baseline to Week 24 in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau) To assess the efficacy of XPro1595 compared with placebo on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)	24 Weeks
Change in brain structure neurodegeneration	Changes from Baseline to Week 24 in volumetric magnetic resonance imaging (MRI) To assess the efficacy of XPro1595 compared with placebo on brain structure neurodegeneration	24 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Goal Attainment Scale (GAS)	Change in individual goals based on the Goal Attainment Scale (GAS) The achievement of each goal is rated on a 5-point attainment scale (-2, -1, 0, +1, +2) to allow standardized scoring of personalized outcomes. A participant's overall goal attainment is quantified using a formula that takes into account the number of goals that have been set, and the extent to which they are correlated with each other. For each identified goal area, the caregiver will be asked to give a detailed description of the patient's current (baseline) status and goal status, which will be recorded at the -1 and 0 levels on the 5-point scale, respectively. The remaining levels of the scale will then be set: somewhat better than the goal (+1), much better than the goal (+2), and much worse than the goal (-2). To evaluate the effect of XPro1595 compared with placebo on goal attainment scores	24 Weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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. Erratum In: JAMA. 2006 Jun 7;295(21):2482.
• 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.

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 (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

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): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Inflammation; TNF
• Additional Relevant MeSH Terms: Pathologic Processes; Dementia; Cognition Disorders; Inflammation; Mental Disorders; Nervous System Diseases; Alzheimer Disease; Cognitive Dysfunction; Brain Diseases; Neurodegenerative Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Tauopathies
• 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