Back to resultsAn Open-Label Extension of XPro1595 in Patients With Alzheimer's Disease
Primary Purpose
Alzheimer Disease, Dementia, Brain Diseases
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
XPro1595
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease focused on measuring Inflammation, Biomarker, Tumor Necrosis Factor (TNF)
Eligibility Criteria
Inclusion Criteria:
Patients are eligible to be included in the study only if all the following criteria apply:
- Participated and completed the full duration of the study intervention and all procedures at the End of Study (EOS) visit in a previous XPro1595 Phase 2 study.
- Concomitant medications for the management MCI/AD and/or behavior symptoms which were ongoing during the double-blind study should remain at a constant dose throughout this study.
- Patient must be willing and able to provide informed consent prior to any study procedures being performed. If the patient is not competent, a LAR (Legally Authorized Representative) must provide informed consent on their behalf, and the patient must provide assent.
- 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. This study partner should agree to monitor and report on concomitant medications, understand the study requirements, and assist the participant in meeting study requirements. Patients with study partners that do not meet this criterion but are determined by the investigator as able to provide an adequate assessment of the patient may also participate with prior approval from the sponsor.
- Male contraception - Agree to use a male condom with female partner use of an additional highly effective contraceptive method with a failure rate of < 1% per year.
- A female participant who is a woman of child-bearing potential (WOBCP) must have a negative highly sensitive pregnancy test (urine) as required by local regulations within 24 hours before the first dose of study intervention, see Section 7.3.6.
Exclusion Criteria:
- Any clinically significant abnormalities that in the opinion of the Investigator require further investigation or treatment or may interfere with study procedures and assessments or affect patient safety. These include but are not limited to, laboratory tests, electrocardiogram (ECG), physical examination, or vital signs at Screening or other medical conditions (e.g., cardiac, respiratory, gastrointestinal, psychiatric, renal disease) which are not adequately and stably controlled.
- Unable to comply with the study procedures and assessments.
Sites / Locations
- KaRa MINDSRecruiting
- Austin Health
- Australian Alzheimer's Research FoundationRecruiting
- Centricity Research
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental: 1.0 mg/kg XPro1595
Arm Description
Patients will receive XPro1595.
Outcomes
Primary Outcome Measures
Number of participants who experience adverse events and serious adverse events
Change from Baseline to Weeks 55, or 74 in the OLE Study
Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram (ECG) findings and other safety assessments will be recorded as adverse events if the findings meet the defined criteria for adverse events.
Secondary Outcome Measures
To evaluate the change in cognitive performance following administration of open-label XPro1595
Change from Baseline on the Early and Mild Alzheimer's Cognitive Composite (EMACC) (Jaeger 2017) made up of the following tests:
The Grocery 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 evaluate the change in cognition and global function following administration of open-label XPro1595
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study for the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)
To evaluate the change in non-cognitive behavioral symptoms following open-label administration of XPro1595
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study on the Neuropsychiatric Inventory (NPI-12) study partner items.
The NPI-12 total score is calculated by adding the scores of the domains (each domain score ranges from 0 to 12). The NPI-12 total score is based upon the first 10 items and ranges from (0 to 10) with higher scores indicating greater behavioral impairment.
To evaluate the change Change from Baseline on the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS- MCI- ADL)
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study on the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS- MCI- ADL)
The 23-item Alzheimer's Disease Cooperative Study - Mild Cognitive Impairment Activities of Daily Living (ADCS-MCI-ADL) Scale has good test-retest reliability, will be utilized to assess performance functioning in MCI patients (Galasko et al., 1997; Douglas Galasko et al., 2006; Pedrosa et al., 2010).
To evaluate the change on blood inflammatory and neurodegeneration biomarkers following open-label administration of XPro1595 (on blood inflammatory and neurodegeneration biomarker amyloid)
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 in the OLE study on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid).
To evaluate the change on blood inflammatory and neurodegeneration biomarkers following open-label administration of XPro1595 (on blood inflammatory and neurodegeneration biomarker pTau)
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 in the OLE study on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau).
To evaluate the change on imaging neuroinflammation following open-label administration of XPro1595
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 in the OLE study in Magnetic Resonance Imaging (MRI) neuroinflammation (White matter Free Water).
To evaluate the change on axonal integrity following open-label administration of XPro1595
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 or in the OLE study in MRI Apparent Fiber Density (AFD).
To evaluate the change in Everyday Cognition (ECog) following open-label administration of XPro1595
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study on Everyday Cognition (ECog).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05522387
Brief Title
An Open-Label Extension of XPro1595 in Patients With Alzheimer's Disease
Official Title
An Open Label Extension of XPro1595 in Patients With Alzheimer's Disease That Have Completed a Phase 1 or Phase 2 Study With XPro1595
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 21, 2023 (Actual)
Primary Completion Date
May 4, 2026 (Anticipated)
Study Completion Date
May 4, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Inmune Bio, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The goal of this Phase 2 Open Label study is to evaluate long-term safety, tolerability, and efficacy of XPro1595 on measures of cognition, function and brain quality in individuals with Alzheimer's Disease.
Detailed Description
This study is designed as a Phase 2, open label study investigating the safety, tolerability, and efficacy of XPro1595 in patients with Alzheimer's Disease (AD). The planned dose is 1.0 mg/kg of XPro1595 for all subjects that completed a previous Phase 1 or Phase 2 study with XPro1595.
Each enrolled patient will be treated with 1.0 mg/kg of XPro1595 as a subcutaneous injection once a week for 55 or 74 weeks, for a total exposure to XPro1595 of up to 78 weeks (18 months), depending on their previous study. Blood sampling for clinical lab analyses, physical exam findings, ECG and C-SSRS will be collected throughout the study to assess the safety and tolerability of XPro1595. Imaging endpoints (MRI), blood sampling for neuroinflammatory and neurodegenerative biomarkers, clinical ratings (CDR-SB, ADCS-MCI ADL, NPI-12) and cognitive performance assessed via the EMACC will be collected at screening and at Weeks 12, 24, 36, and 48. Depending on the parent study, some or all of these assessments may also be made at Weeks 55, 60 or 74.
All patients that completed 4 weeks of dosing and the week 5 PK draw in the Phase 1 PK Lead-In or completed the treatment period and End of Study (EOS) assessments in a Phase 2 study are eligible to enroll into the OLE study. All patients enrolled, including those treated with placebo in the parent study, will receive 1.0 mg/kg XPro1595. Randomized treatment will remain blinded until the parent study database is locked, the study is unblinded and results for their prior study are released.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders
Keywords
Inflammation, Biomarker, Tumor Necrosis Factor (TNF)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
An Open-Label Extension of XPro1595 in Patients with Alzheimer's Disease (AD) That Have Completed a Phase 2 Study with XPro1595
Masking
None (Open Label)
Allocation
N/A
Enrollment
261 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental: 1.0 mg/kg XPro1595
Arm Type
Experimental
Arm Description
Patients will receive XPro1595.
Intervention Type
Drug
Intervention Name(s)
XPro1595
Other Intervention Name(s)
INB03/XPro™, XENP1595, DN-TNF
Intervention Description
Each enrolled patient will be treated with 1.0 mg/kg of XPro1595 as a subcutaneous injection once a week for 55, or 74 weeks, for a total exposure to XPro1595 of up to 78 weeks (18 months), depending on their previous study.
Primary Outcome Measure Information:
Title
Number of participants who experience adverse events and serious adverse events
Description
Change from Baseline to Weeks 55, or 74 in the OLE Study
Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram (ECG) findings and other safety assessments will be recorded as adverse events if the findings meet the defined criteria for adverse events.
Time Frame
Weeks 55, or 74 in the OLE Study
Secondary Outcome Measure Information:
Title
To evaluate the change in cognitive performance following administration of open-label XPro1595
Description
Change from Baseline on the Early and Mild Alzheimer's Cognitive Composite (EMACC) (Jaeger 2017) made up of the following tests:
The Grocery 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)
Time Frame
Week 55 in the OLE Study
Title
To evaluate the change in cognition and global function following administration of open-label XPro1595
Description
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study for the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)
Time Frame
Week 55 in the OLE Study
Title
To evaluate the change in non-cognitive behavioral symptoms following open-label administration of XPro1595
Description
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study on the Neuropsychiatric Inventory (NPI-12) study partner items.
The NPI-12 total score is calculated by adding the scores of the domains (each domain score ranges from 0 to 12). The NPI-12 total score is based upon the first 10 items and ranges from (0 to 10) with higher scores indicating greater behavioral impairment.
Time Frame
Week 55 in the OLE Study
Title
To evaluate the change Change from Baseline on the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS- MCI- ADL)
Description
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study on the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS- MCI- ADL)
The 23-item Alzheimer's Disease Cooperative Study - Mild Cognitive Impairment Activities of Daily Living (ADCS-MCI-ADL) Scale has good test-retest reliability, will be utilized to assess performance functioning in MCI patients (Galasko et al., 1997; Douglas Galasko et al., 2006; Pedrosa et al., 2010).
Time Frame
Week 55 in the OLE Study
Title
To evaluate the change on blood inflammatory and neurodegeneration biomarkers following open-label administration of XPro1595 (on blood inflammatory and neurodegeneration biomarker amyloid)
Description
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 in the OLE study on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid).
Time Frame
Weeks 55, or 74 in the OLE Study
Title
To evaluate the change on blood inflammatory and neurodegeneration biomarkers following open-label administration of XPro1595 (on blood inflammatory and neurodegeneration biomarker pTau)
Description
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 in the OLE study on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau).
Time Frame
Weeks 55, or 74 in the OLE Study
Title
To evaluate the change on imaging neuroinflammation following open-label administration of XPro1595
Description
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 in the OLE study in Magnetic Resonance Imaging (MRI) neuroinflammation (White matter Free Water).
Time Frame
Weeks 55, or 74 in the OLE Study
Title
To evaluate the change on axonal integrity following open-label administration of XPro1595
Description
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 or in the OLE study in MRI Apparent Fiber Density (AFD).
Time Frame
Weeks 55, or 74 in the OLE Study
Title
To evaluate the change in Everyday Cognition (ECog) following open-label administration of XPro1595
Description
Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study on Everyday Cognition (ECog).
Time Frame
Week 55 in the OLE Study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
86 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients are eligible to be included in the study only if all the following criteria apply:
Participated and completed the full duration of the study intervention and all procedures at the End of Study (EOS) visit in a previous XPro1595 study.
Concomitant medications for the management of MCI/AD and/or behavior symptoms which were ongoing during the double-blind study should remain at a constant dose throughout this study.
Patient must be willing and able to provide informed consent prior to any study procedures being performed. If the patient is not competent, a LAR (Legally Authorized Representative) must provide informed consent on their behalf, and the patient must provide assent.
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. This study partner should agree to monitor and report on concomitant medications, understand the study requirements, and assist the participant in meeting study requirements. Patients with study partners that do not meet this criterion but are determined by the investigator as able to provide an adequate assessment of the patient may also participate with prior approval from the sponsor (However, this is not a requirement for patients coming from the AD-02 PK Lead-In Study).
All male subjects who are sexually active with a female of childbearing potential (FCBP) must agree to use a highly effective method of contraception during the treatment period and until 90 days after the last dose of treatment.
All females of childbearing potential (FCBP) must have a negative urine pregnancy test and agree to use a highly effective method of contraception during the treatment period and 30 days after the last dose of treatment.
Exclusion Criteria:
Any clinically significant abnormalities that in the opinion of the Investigator require further investigation or treatment or may interfere with study procedures and assessments or affect patient safety. These include but are not limited to, laboratory tests, electrocardiogram (ECG), physical examination, or vital signs at Screening or other medical conditions (e.g., cardiac, respiratory, gastrointestinal, psychiatric, renal disease) which are not adequately and stably controlled.
Unable to comply with the study procedures and assessments.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
INmune Bio, Inc.
Phone
(858)964-3720
Email
trials@inmunebio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tara Lehner
Organizational Affiliation
INmune Bio
Official's Role
Study Director
Facility Information:
Facility Name
KaRa MINDS
City
Macquarie Park
State/Province
New South Wales
ZIP/Postal Code
2113
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katrina Craft
Phone
02 8960 7788
Email
katarina.kraft@karaminds.com.au
Facility Name
Austin Health
City
Ivanhoe
State/Province
Victoria
ZIP/Postal Code
3079
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Margison
Phone
61 3 9496 2823
Email
Laura.margison@austin.org.au
Facility Name
Australian Alzheimer's Research Foundation
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isabella Sabbagh
Phone
61 8 938 96433
Email
Isabella.sabbagh@alzheimers.com.au
Facility Name
Centricity Research
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4G 3E8
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giovanni Marotta
Phone
(416)294-0724
Email
marottaresearch@centricityresearch.com
12. IPD Sharing Statement
Plan to Share IPD
No
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https://www.alz.org/alzheimers-dementia/facts-figures
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Alzheimer's Association annual report releasing statistics regarding Alzheimer's disease
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An Open-Label Extension of XPro1595 in Patients With Alzheimer's Disease
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