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A Biomarker-directed Study of XPro1595 in Patients With Mild to Moderate Alzheimer's

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03943264
Recruitment Status : Recruiting
First Posted : May 9, 2019
Last Update Posted : June 13, 2019
Sponsor:
Collaborator:
Alzheimer's Association
Information provided by (Responsible Party):
Inmune Bio, Inc.

Brief Summary:
The purpose of this study is to evaluate safety and target engagement of XPro1595 in Alzheimer's patients with biomarkers of inflammation.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: XPro1595 Phase 1

Detailed Description:

The study is designed as a multicentre, phase 1b open-label study. The objectives of this study are to determine the safety, tolerability, and efficacy of XPro1595 in patients with mild to moderate Alzheimer's disease and elevated blood levels of the inflammatory biomarker high sensitivity c-reactive protein (hs-CRP).

XPro1595 is a second-generation inhibitor of tumor necrosis factor (TNF) that selectively neutralizes soluble TNF, an inflammatory factor implicated in Alzheimer's pathology.

A key element of this study is to identify Alzheimer's patients that are most likely to benefit from XPro1595 treatment. Enrollment is limited to patients with evidence of peripheral inflammation using elevated blood hs-CRP as a biomarker of neuroinflammation. hs-CRP is an inflammatory biomarker elevated in the blood of some Alzheimer's patients and elevated CRP has been shown to predict response to TNF inhibitors in multiple other diseases.

Alzheimer's patients with elevated blood hs-CRP will be enrolled in a 12-week study to determine the safety and the ability of XPro1595 to reduce neuroinflammation using a combination of invasive and non-invasive biomarkers of inflammation. The study will identify the dose of XPro1595 to be used in a larger Phase II disease modification study.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b Open-Label, Dose-Identification Study of XPro1595 in Patients With Mild to Moderate Alzheimer's Disease With Elevated High Sensitivity C-reactive Protein in Blood
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 0.3 mg/kg XPro1595
0.3 mg/kg of XPro1595 will be administered via subcutaneous injection once a week for 12 weeks.
Drug: XPro1595
XPro1595 will be delivered by subcutaneous injection once a week
Other Name: INB03, DN-TNF, XENP345

Experimental: 1.0 mg/kg XPro1595
1.0 mg/kg of XPro1595 will be administered via subcutaneous injection once a week for 12 weeks.
Drug: XPro1595
XPro1595 will be delivered by subcutaneous injection once a week
Other Name: INB03, DN-TNF, XENP345

Experimental: 3.0 mg/kg XPro1595
3.0 mg/kg of XPro1595 will be administered via subcutaneous injection once a week for 12 weeks.
Drug: XPro1595
XPro1595 will be delivered by subcutaneous injection once a week
Other Name: INB03, DN-TNF, XENP345




Primary Outcome Measures :
  1. The number of patients with a treatment-emergent adverse event throughout 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    Adverse events will be assessed by clinical and laboratory measures

  2. The percentage of patients with a treatment-emergent adverse event throughout 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    Adverse events will be assessed by clinical and laboratory measures


Secondary Outcome Measures :
  1. Changes from baseline in high sensitivity C-reactive protein in the blood and cerebral spinal fluid following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    To compare changes in high sensitivity C-reactive protein

  2. Changes from baseline in inflammatory cytokines in the blood and cerebral following 12 weeks of treatment with XPro1595 spinal fluid [ Time Frame: 12 weeks ]
    To compare changes in Inflammatory cytokines; including but not limited to tumor necrosis factor, interleukin-1, and interleukin-6

  3. Changes from baseline in blood and cerebral spinal fluid levels of amyloid beta following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    To compare changes in amyloid in cerebral spinal fluid

  4. Changes from baseline in cerebral spinal fluid levels of tau following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    To compare changes in tau in cerebral spinal fluid

  5. Change from baseline in FreeWater content (edema) using magnetic resonance imaging following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    To compare changes in FreeWater content as a proxy of neuroinflammation following 12 weeks of treatment with XPro1595

  6. Change from baseline in the Mini-Mental State Examination (MMSE) following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    The Mini-Mental State Examination (MMSE) provides a comprehensive measure of cognitive function. The maximum possible score is 30 and patients scoring below 23 are classified as having cognitive impairment as follows, mild (19 to 23), moderate (10 to 18), severe (below 9).

  7. Change from baseline in the Digit Symbol Substitution Test (DSST) following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    The Digit Symbol Substitution Test (DSST) is a cognitive test that consists of digit-symbol pairs. The patient records the corresponding symbol to each presented digit in 90 seconds. The total number of correct symbols is counted to provide a score between 0 and 133. Higher scores indicate better cognitive functioning.

  8. Change from baseline in the Verbal Fluency Test following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    In the Verbal Fluency Test, patients are given a letter and asked to name as many words as they can that begin with that letter in 60 seconds. The number of correct responses is counted. A higher number of responses indicates better cognitive functioning.

  9. Change from baseline in the Neuropsychiatric Inventory (NPI) following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    Neuropsychiatric Inventory (NPI) is a measure of frequency and severity of common psychiatric symptoms related to dementia using a 12-question measure. For each question, a score is given for frequency, severity and caregiver distress. Total scores range from 0 to 144. A higher score means greater neuropsychiatric disturbance.

  10. Change from baseline in the Bristol Activities of Daily Living Scale (BALDS) following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    Bristol Activities of Daily Living Scale (BADLS) is a questionnaire that measures the impact of Alzheimer's disease on daily activities using a 20-item questionnaire. Total scores range from 0 to 60. A higher score indicates a greater disturbance in daily living.

  11. Change from baseline in the Memory-Enhanced Retrospective Evaluation of Treatment Observer Reported Global Impression of Improvement (MERET OBSRO-C) following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    Memory-Enhanced Retrospective Evaluation of Treatment Observer Reported Global Impression of Improvement (MERET OBSRO-C) evaluates caregivers' self-reports of treatment efficacy with self-prompted memory aids regarding their clinical experiences obtained prior to treatment initiation.

  12. Evaluate changes in the Memory-Enhanced Retrospective Evaluation of Change from baseline Global Impression of Improvement (MERET PGI-C) following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    Memory-Enhanced Retrospective Evaluation of Treatment Patient Global Impression of Improvement (MERET PGI-C) evaluates patients self-reports of treatment efficacy with self-prompted memory aids regarding their clinical experience obtained prior to treatment initiation. Patient's global impression of (PGI-I) ratings will be obtained using a web-based interface prior to and following playback of impromptu patient recordings obtained prior to the start of treatment (MERET).


Other Outcome Measures:
  1. Change from baseline in Breath volatile organic compounds (BVOCs) following 12 weeks of treatment with XPro1595 [ Time Frame: 12 weeks ]
    Breath volatile organic compounds (BVOCs) is a non-invasive method of measuring biological processes in exhaled breath that can be used to inform on disease and treatment-related states.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 50 to 80 (inclusive) at screening;
  • Weight range within 40 kg to 100 kg (inclusive);
  • Diagnosed with probable AD defined by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria;
  • Confirmed positive amyloid detection;
  • Mild to moderate AD (Mini-Mental State Examination score of 13 to 24);
  • Has hsCRP levels ≥ 2 mg/L;
  • All female patients must be post-menopausal and all male subjects must be on acceptable contraception during the treatment period.
  • Consents to having lumbar punctures;
  • Consents to apolipoprotein E (ApoE) genotyping if no previous results are available;
  • Provide written informed consent prior to any study procedures being performed.
  • Has a caregiver who either lives in the same household or interacts with the patient at least 4 hours per day and at least 4 days per week, who is knowledgeable about the participant's daytime and night-time behaviors and who can be available to attend all clinic visits in person. Patients with caregivers 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.

Exclusion Criteria:

  • Patients taking cholinesterase inhibitors, memantine, or antidepressant medication for less than 90 days;
  • Have taken within the last 90 days; corticosteroids or other immunosuppressive drugs, thalidomide or other TNF active drugs, minocycline;
  • Enrolled in another clinical trial where patients receive treatment with investigational drug or device or have received treatment on another AD clinical trial within the last 90 days
  • Unable to tolerate lumbar puncture or taking medicine where lumbar punctures are contraindicated (anti-coagulants besides daily 100 mg of aspirin);
  • A prior organ or stem cell transplant;
  • A major adverse cardiac event within 6 months before screening;
  • Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ that have been resected with no evidence of metastatic disease for 3 years;
  • Jaundice, active hepatitis, or known hepatobiliary disease (except asymptomatic cholelithiasis);
  • Positive screening assessment for viral hepatitis B surface antigen or hepatitis C virus (HCV) antibody and positive HCV ribonucleic acid or human immunodeficiency virus, or a history of illicit drug injecting;
  • Seated blood pressure of ≥ 165/105 mmHg at screening;
  • Body mass index ≥ 35 kg/m2 at screening;
  • Unable to comply with the study procedures and assessments;
  • Known hypersensitivity to investigational product or its excipients;
  • Any other disease, a physical or psychological condition that the investigator or sponsor believes may contraindicate the use of the XPro1595 or affect the interpretation of study results or render the patient at high risk from treatment complications;
  • Any investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03943264


Contacts
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Contact: CJ Barnum, PhD +61 8 6555 9500 trials@inmunebio.com

Locations
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Australia, New South Wales
KaRa MINDS Recruiting
Macquarie Park, New South Wales, Australia, 2113
Principal Investigator: Rosalyn Lai, MD         
Australia, South Australia
Central Adelaide Local Health Network Not yet recruiting
Woodville, South Australia, Australia, 5011
Principal Investigator: Cathy Short, MD         
Australia, Victoria
Austin Health Not yet recruiting
Heidelberg Heights, Victoria, Australia, 3081
Principal Investigator: Michael Woodward, MD         
Alfred Heath Not yet recruiting
Melbourne, Victoria, Australia, 3004
Principal Investigator: Terrence O'Brien, MD         
Australia, Western Australia
The Australian Alzheimer's Research Foundation Not yet recruiting
Nedlands, Western Australia, Australia, 6009
Principal Investigator: Roger Clarnette, MD         
Sponsors and Collaborators
Inmune Bio, Inc.
Alzheimer's Association
Investigators
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Principal Investigator: Terrence O'Brien, MD The Alfred

Additional Information:
Publications of Results:
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Responsible Party: Inmune Bio, Inc.
ClinicalTrials.gov Identifier: NCT03943264     History of Changes
Other Study ID Numbers: XPRO1595-AD
18PTC-R-592167 ( Other Grant/Funding Number: Alzheimer's Association )
First Posted: May 9, 2019    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Inmune Bio, Inc.:
inflammation
Biomarker
TNF
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders