Clinical trial NCT05321498: Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation
Official title: A Phase 2, Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients With Mild Cognitive Impairment (MCI) With Biomarkers of Inflammation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Mild Cognitive Impairment (MCI)
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Mental Disorders
Keywords: Inflammation
Biomarker
Tumor Necrosis Factor (TNF)
Lead sponsor: Inmune Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-11
Enrollment: 0
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: * (2:1) XPro1595 (1mg/kg), placebo
* Weekly subcutaneous injections
Primary purpose: TREATMENT

Brief summary: The goal of this Phase 2 MCI study is to determine whether 1.0 mg/kg XPro1595 is superior to placebo at improving measures of cognition, functioning and brain quality in individuals with MCI and biomarkers associated with neuroinflammation (APOE4) and to evaluate safety, tolerability, and efficacy of XPro1595.

Detailed description: This study is designed as a Phase 2, double-blind randomized, placebo-controlled study investigating the safety, tolerability, and efficacy of XPro1595 in patients with MCI. The planned dose is 1.0 mg/kg of XPro1595 and matching placebo.

Eligibility criteria: Inclusion Criteria:

Patients are eligible to be included in the study only if all the following criteria apply:

* Adult male and female patients ≥ 55 years to ≤ 80 years of age at the time of consent;
* Diagnosed with MCI of probable Alzheimer's disease (Albert 2011; National Institute on Aging - Alzheimer's Association \[NIA-AA\]). Patients who have received previous therapy for Alzheimer's disease may still be eligible;
* Amyloid positive (documented in medical history or assessed during screening through blood test);
* Literate and capable of reading, writing, and communicating effectively with others, based on the PI's assessment;
* Has a study partner willing to participate 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 informant assessments are performed.

Exclusion Criteria:

* 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 at the strength required for this study);
* 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: has answered "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation items 4 or 5, or any suicidal behavior within 6 months before Screening, at Screening, or at the Week 1 Visit, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening;
* 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

Primary outcomes:
measure: Change in Early and Mild Alzheimer's Cognitive Composite (EMACC)
timeFrame: 12 Weeks
Secondary outcomes:
measure: Change in Mean Computer-based Cognitive Assessment (Cogstate) Composite score from Screening to Week 12
timeFrame: 12 Weeks
measure: Change in myelin content
timeFrame: 12 Weeks
measure: Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid)
timeFrame: 12 Weeks
measure: Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)
timeFrame: 12 Weeks
measure: Change in Imaging (MRI) Neuroinflammation
timeFrame: 12 Weeks
measure: Change in imaging markers of brain quality
timeFrame: 12 Weeks
measure: Change in apparent fiber density (AFD)
timeFrame: 12 Weeks
measure: Change in non-cognitive behavioral symptoms
timeFrame: 12 Weeks
measure: Change in brain activity
timeFrame: 12 Weeks
measure: Change in speech and language
timeFrame: 12 Weeks
measure: Change in Alzheimer's Disease Cooperative Study - Mild Cognitive Impairment Activities of Daily Living (ADCS-MCI ADL)
timeFrame: 12 Weeks
measure: Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)
timeFrame: 12 Weeks
measure: Number of participants who experience adverse events and serious adverse events
timeFrame: Screening up to 28 days post last dose
Other outcomes:
measure: Change in Goal Attainment Scale (GAS)
timeFrame: 12 Weeks
measure: Change in measures of activity
timeFrame: 12 Weeks
measure: Evaluate predictability of patient response after placebo administration and potential influence of study partners on outcome evaluation using the Multidimensional Psychological Questionnaire (MPsQ) with a 5 point scale
timeFrame: 12 Weeks
Locations:
Study officials:
affiliation: INmune Bio
name: Tara Lehner
role: STUDY_DIRECTOR
References:
citation: Alvarez A, Cacabelos R, Sanpedro C, Garcia-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging. 2007 Apr;28(4):533-6. doi: 10.1016/j.neurobiolaging.2006.02.012. Epub 2006 Mar 29.
citation: 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.
citation: Buchhave P, Zetterberg H, Blennow K, Minthon L, Janciauskiene S, Hansson O. Soluble TNF receptors are associated with Abeta metabolism and conversion to dementia in subjects with mild cognitive impairment. Neurobiol Aging. 2010 Nov;31(11):1877-84. doi: 10.1016/j.neurobiolaging.2008.10.012. Epub 2008 Dec 13.
citation: 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.