Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation

NCT05321498 | Withdrawn Phase 2 DMC

• 1 other identifier: XPro1595-AD-03
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

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)

Outcome Measures

Primary Outcomes (1)

• Change in Early and Mild Alzheimer's Cognitive Composite (EMACC)

  Change from Baseline to Week 12 in the Early and Mild Alzheimer's Cognitive Composite (EMACC) (Jaeger 2017) made up of the following tests: * International Shopping List Test- Immediate recall (Word List Learning Test-Immediate recall) * Trail Making Test Part A and B * Digit Symbol Coding Test * Digit Span Forward and Backward * Category Fluency Test (DKEFS) * Letter Fluency Test (DKEFS) To assess the efficacy of XPro1595 compared with placebo on cognitive performance in patients with MCI

  12 Weeks

Secondary Outcomes (13)

• Change in Mean Computer-based Cognitive Assessment (Cogstate) Composite score from Screening to Week 12

  12 Weeks

• Change in myelin content

  12 Weeks

• Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid)

  12 Weeks

• Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)

  12 Weeks

• Change in Imaging (MRI) Neuroinflammation

  12 Weeks

Other Outcomes (3)

• Change in Goal Attainment Scale (GAS)

  12 Weeks

• Change in measures of activity

  12 Weeks

• 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

  12 Weeks

Study Arms (2)

1.0 mg/kg XPro1595

EXPERIMENTAL

1.0 mg/kg XPro1595 will be administered via subcutaneous injection once a week for 12 weeks.

Drug: XPro1595

1.0 mg/kg Placebo

PLACEBO COMPARATOR

1.0 mg/kg of Placebo will be administered via subcutaneous injection once a week for 12 weeks.

Drug: Placebo

Interventions

XPro1595 DRUG

XPro1595 will be delivered by subcutaneous injection once a week.

Also known as: INB03/XPro™, XENP1595, Dominant-negative Tumor Necrosis Factor (DN-TNF)

1.0 mg/kg XPro1595

Placebo DRUG

Placebo will be delivered by subcutaneous injection once a week

Also known as: Matching Placebo

1.0 mg/kg Placebo

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Inmune Bio, Inc.: lead

Related Publications (4)

• 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.

  PMID: 16569464 BACKGROUND

• 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.

  PMID: 16705109 BACKGROUND

• 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.

  PMID: 19070941 BACKGROUND

• 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.

  PMID: 21239393 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Mental Disorders; Inflammation

Interventions

XENP 1595

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tara Lehner

  INmune Bio

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * (2:1) XPro1595 (1mg/kg), placebo * Weekly subcutaneous injections

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: April 11, 2022
• Study Start: June 1, 2023
• Primary Completion: October 26, 2023
• Study Completion: October 26, 2023
• Last Updated: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share