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Alzheimer DiseasePhase 2NCT05522387

An Open-Label Extension of XPro1595 in Patients With Alzheimer's Disease

A Phase 2 study testing XPro1595 in people with Alzheimer Disease and Dementia, run by Inmune Bio, Inc. at 4 sites in Australia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 55 to 86 years
Conditions the study is for
Alzheimer Disease, Dementia, Brain Diseases
What is being tested?
XPro1595
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
4 sitesAustralia
Study dates
21 Feb 2023to 5 Jul 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 86 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

4 sites in 1 country.

Australia4 sites

  • Neuro Trials Victoria Pty Ltd T/A NeuroCentrix

    Carlton, Victoria, 3053

  • Austin Health

    Ivanhoe, Victoria, 3079

  • KaRa MINDS

    Macquarie Park, New South Wales, 2113

  • Australian Alzheimer's Research Foundation

    Perth, Western Australia, 6009

Other trials in Australia

About this study

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

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.

Read the 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.

Being tested
XPro1595
Keywords
Inflammation, Biomarker, Tumor Necrosis Factor (TNF)
Medical subject headings
Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Neurodegenerative Diseases, Neurocognitive Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • XPro1595Drug

    Also called INB03/XPro™, XENP1595, DN-TNF

    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.

Study groups in NCT05522387
Study groupRoleWhat they receive
Experimental: 1.0 mg/kg XPro1595ExperimentalPatients will receive XPro1595.
Receives: Drug: XPro1595

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Weeks 55, or 74 in the OLE Study

Secondary outcomes (9)

  1. 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)

    Measured: Week 55 in the OLE Study

  2. 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)

    Measured: Week 55 in the OLE Study

  3. 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.

    Measured: Week 55 in the OLE Study

  4. 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).

    Measured: Week 55 in the OLE Study

  5. 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).

    Measured: Weeks 55, or 74 in the OLE Study

  6. 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).

    Measured: Weeks 55, or 74 in the OLE Study

  7. 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).

    Measured: Weeks 55, or 74 in the OLE Study

  8. 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).

    Measured: Weeks 55, or 74 in the OLE Study

  9. 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).

    Measured: Week 55 in the OLE Study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2022
  2. Study start21 Feb 2023
  3. Primary completion5 Jun 2024
  4. Study completion5 Jul 2024

Why it stopped: Sponsor resource allocation

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
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)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05522387
Sponsor's protocol ID
XPro1595-AD-OLE
Status last verified
Feb 2026
First submitted
18 Aug 2022
Last updated
27 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 16705109

  • 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.

    PubMed 21239393

  • 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.

    PubMed 27470609

  • 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.

    PubMed 22966039

  • 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.

    PubMed 16569464

  • 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.

    PubMed 19070941

  • Branders S, Bernard G and Pereira A. Leveraging historical data for high-dimensional regression adjustment, a machine learning approach. PSI annual conference, Amsterdam, 3 to 6 June 2018.

  • Arnason et al., Neurology. 53, 457-465 (1999)

  • Bradshaw MJ, Mobley BC, Zwerner JP, Sriram S. Autopsy-proven demyelination associated with infliximab treatment. Neurol Neuroimmunol Neuroinflamm. 2016 Jan 27;3(2):e205. doi: 10.1212/NXI.0000000000000205. eCollection 2016 Apr. No abstract available.

    PubMed 26894207

  • Dickson DW. The pathogenesis of senile plaques. J Neuropathol Exp Neurol. 1997 Apr;56(4):321-39. doi: 10.1097/00005072-199704000-00001.

    PubMed 9100663

  • Draft FDA Guidance for Industry: Adjusting for covariates in randomized clinical trials for drugs and biologics. Revision 1 May 2021 Biostatistics (https://www.fda.gov/media/148910/download).

  • Finsterwalder S, Vlegels N, Gesierich B, Araque Caballero MA, Weaver NA, Franzmeier N, Georgakis MK, Konieczny MJ, Koek HL; Dominantly Inherited Alzheimer Network (DIAN); Karch CM, Graff-Radford NR, Salloway S, Oh H, Allegri RF, Chhatwal JP; DELCODE study group; Jessen F, Duzel E, Dobisch L, Metzger C, Peters O, Incesoy EI, Priller J, Spruth EJ, Schneider A, Fliessbach K, Buerger K, Janowitz D, Teipel SJ, Kilimann I, Laske C, Buchmann M, Heneka MT, Brosseron F, Spottke A, Roy N, Ertl-Wagner B, Scheffler K; Alzheimer's Disease Neuroimaging Initiative (ADNI); Utrecht VCI study group; Seo SW, Kim Y, Na DL, Kim HJ, Jang H, Ewers M, Levin J, Schmidt R, Pasternak O, Dichgans M, Biessels GJ, Duering M. Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients. Alzheimers Dement. 2020 Nov;16(11):1504-1514. doi: 10.1002/alz.12150. Epub 2020 Aug 18.

    PubMed 32808747

  • Fillit H, Ding WH, Buee L, Kalman J, Altstiel L, Lawlor B, Wolf-Klein G. Elevated circulating tumor necrosis factor levels in Alzheimer's disease. Neurosci Lett. 1991 Aug 19;129(2):318-20. doi: 10.1016/0304-3940(91)90490-k.

    PubMed 1745413

  • Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018.

    PubMed 29653606

  • James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee WM. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos. 2009 Aug;37(8):1779-84. doi: 10.1124/dmd.108.026195. Epub 2009 May 13.

    PubMed 19439490

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing XPro1595 in people with Alzheimer Disease and Dementia, run by Inmune Bio, Inc. at 4 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor resource allocation). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants who experience adverse events and serious adverse events (time frame: Weeks 55, or 74 in the OLE Study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05522387, which also lists 47 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.

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