Clinical trial NCT05318976: A Study of XPro1595 in Patients with Early Alzheimer's Disease with Biomarkers of Inflammation
Official title: A Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients with Early Alzheimer's Disease with Biomarkers of Inflammation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Mild Cognitive Impairment
Keywords: Inflammation
Biomarker
TNF
Lead sponsor: Inmune Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-08
Enrollment: 201
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Early and Mild Alzheimer's Cognitive Composite (EMACC)
timeFrame: 24 Weeks
Secondary outcomes:
measure: Change in Clinical Dementia Rating (CDR)
timeFrame: 24 Weeks
measure: Change in apparent fiber density (AFD)
timeFrame: 24 Weeks
measure: Change in Everyday Cognition (E-Cog)
timeFrame: 24 Weeks
measure: Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-MCI-ADL)
timeFrame: 24 Weeks
measure: Change in myelin content
timeFrame: 24 Weeks
measure: Change in non-cognitive behavioral symptoms
timeFrame: 24 Weeks
measure: Change in gray matter integrity
timeFrame: 24 Weeks
measure: Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid)
timeFrame: 24 Weeks
measure: Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)
timeFrame: 24 Weeks
measure: Change in brain structure neurodegeneration
timeFrame: 24 Weeks
measure: Number of participants who experience adverse events and serious adverse events
timeFrame: Baseline up to 28 days post last dose
Other outcomes:
measure: Change in Goal Attainment Scale (GAS)
timeFrame: 24 Weeks
Locations:
city: Darlinghurst
country: Australia
facility: INmune Bio Investigational Site
state: New South Wales
city: Macquarie Park
country: Australia
facility: INmune Bio Investigational Site
state: New South Wales
city: Adelaide
country: Australia
facility: INmune Bio Investigational Site
state: South Australia
city: Box Hill
country: Australia
facility: INmune Bio Investigational Site
state: Victoria
city: Carlton
country: Australia
facility: INmune Bio Investigational Site
state: Victoria
city: Ivanhoe
country: Australia
facility: INmune Bio Investigational Site
state: Victoria
city: Parkville
country: Australia
facility: INmune Bio Investigational Site
state: Victoria
city: Perth
country: Australia
facility: INmune Bio Investigational Site
state: Western Australia
city: Kelowna
country: Canada
facility: INmune Bio Investigational Site
city: Ottawa
country: Canada
facility: INmune Bio Investigational Site
city: Sherbrooke
country: Canada
facility: INmune Bio Investigational Site
city: Toronto
country: Canada
facility: INmune Bio Investigational Site
city: Toronto
country: Canada
facility: INmune Bio Investigational Site
city: West Vancouver
country: Canada
facility: INmune Bio Investigational Site
city: Brno
country: Czechia
facility: INmune Bio Investigational Site
city: Plzen
country: Czechia
facility: INmune Bio Investigational Site
city: Prague
country: Czechia
facility: INmune Bio Investigational Site
city: Praha
country: Czechia
facility: INmune Bio Investigational Site
city: Rychnov Nad Kněžnou
country: Czechia
facility: INmune Bio Investigational Site
city: Bron
country: France
facility: INmune Bio Investigational Site
city: Nantes
country: France
facility: INmune Bio Investigational Site
city: Toulouse
country: France
facility: INmune Bio Investigational Site
city: Berlin
country: Germany
facility: INmune Bio Investigational Site
city: Chemnitz
country: Germany
facility: INmune Bio Investigational Site
city: Białystok
country: Poland
facility: INmune Bio Investigational Site
city: Bydgoszcz
country: Poland
facility: INmune Bio Investigational Site
city: Wrocław
country: Poland
facility: INmune Bio Investigational Site
city: Barcelona
country: Spain
facility: INmune Bio Investigational Site
city: Barcelona
country: Spain
facility: INmune Bio Investigational Site
city: Córdoba
country: Spain
facility: INmune Bio Investigational Site
city: Madrid
country: Spain
facility: INmune Bio Investigational Site
city: Sevilla
country: Spain
facility: INmune Bio Investigational Site
city: Valencia
country: Spain
facility: INmune Bio Investigational Site
city: Valencia
country: Spain
facility: INmune Bio Investigational Site
city: Birmingham
country: United Kingdom
facility: INmune Bio Investigational Site
city: Bristol
country: United Kingdom
facility: INmune Bio Investigational Site
city: Guildford
country: United Kingdom
facility: INmune Bio Investigational Site
city: London
country: United Kingdom
facility: INmune Bio Investigational Site
city: Motherwell
country: United Kingdom
facility: INmune Bio Investigational Site
city: Plymouth
country: United Kingdom
facility: INmune Bio Investigational Site
city: Winchester
country: United Kingdom
facility: INmune Bio Investigational Site
Study officials:
affiliation: INmune Bio
name: Therese Blomberg
role: STUDY_DIRECTOR
References:
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: 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.
citation: 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.
citation: 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.