A Study of XPro1595 in Patients with Early Alzheimer's Disease with Biomarkers of Inflammation
- Conditions
- Alzheimer DiseaseDementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental DisordersMild Cognitive Impairment
- Interventions
- Drug: Placebo
- Registration Number
- NCT05318976
- Lead Sponsor
- Inmune Bio, Inc.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 201
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.
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1.0 mg/kg XPro1595 XPro1595 1.0 mg/kg of XPro1595 will be administered via subcutaneous injection once a week for 23 weeks. 1.0 mg/kg Placebo Placebo 1.0 mg/kg of Placebo will be administered via subcutaneous injection once a week for 23 weeks.
- Primary Outcome Measures
Name Time Method Change in Early and Mild Alzheimer's Cognitive Composite (EMACC) 24 Weeks 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 early ADi
- Secondary Outcome Measures
Name Time Method Change in apparent fiber density (AFD) 24 Weeks 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 early ADiChange in Clinical Dementia Rating (CDR) 24 Weeks 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 early ADiChange in Everyday Cognition (E-Cog) 24 Weeks Change from Baseline to Week 24 in Everyday Cognition (E-Cog)
To evaluate the effect of XPro1595 compared with placebo on E-CogChange in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-MCI-ADL) 24 Weeks Change from Baseline to Week 24 in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-MCI-ADL)
To assess the effect of XPro1595 compared with placebo on ADL in patients with early ADi.Change in myelin content 24 Weeks 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 early ADi.Change in non-cognitive behavioral symptoms 24 Weeks 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 early ADiChange in gray matter integrity 24 Weeks 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 early ADiChange in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid) 24 Weeks 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).Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau) 24 Weeks 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)Change in brain structure neurodegeneration 24 Weeks Changes from Baseline to Week 24 in volumetric magnetic resonance imaging (MRI)
To assess the efficacy of XPro1595 compared with placebo on brain structure neurodegenerationNumber of participants who experience adverse events and serious adverse events Baseline up to 28 days post last dose 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.
Trial Locations
- Locations (1)
INmune Bio Investigational Site
🇬🇧Winchester, United Kingdom