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

NCT03943264 | Completed Phase 1 DMC

• 2 other identifiers: XPRO1595-AD18PTC-R-592167
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Alzheimer Disease

Keywords

inflammation; Biomarker; TNF

Outcome Measures

Primary Outcomes (2)

• The number of patients with a treatment-emergent adverse event throughout 12 weeks of treatment with XPro1595

  Adverse events will be assessed by clinical and laboratory measures

  12 weeks

• The percentage of patients with a treatment-emergent adverse event throughout 12 weeks of treatment with XPro1595

  Adverse events will be assessed by clinical and laboratory measures

  12 weeks

Secondary Outcomes (12)

• Changes from baseline in high sensitivity C-reactive protein in the blood and cerebral spinal fluid following 12 weeks of treatment with XPro1595

  12 weeks

• Changes from baseline in inflammatory cytokines in the blood and cerebral following 12 weeks of treatment with XPro1595 spinal fluid

  12 weeks

• Changes from baseline in blood and cerebral spinal fluid levels of amyloid beta following 12 weeks of treatment with XPro1595

  12 weeks

• Changes from baseline in cerebral spinal fluid levels of tau following 12 weeks of treatment with XPro1595

  12 weeks

• Change from baseline in FreeWater content (edema) using magnetic resonance imaging following 12 weeks of treatment with XPro1595

  12 weeks

Other Outcomes (1)

• Change from baseline in Breath volatile organic compounds (BVOCs) following 12 weeks of treatment with XPro1595

  12 weeks

Study Arms (3)

0.3 mg/kg XPro1595

EXPERIMENTAL

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

Drug: XPro1595

0.6 mg/kg XPro1595

EXPERIMENTAL

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

Drug: XPro1595

1.0 mg/kg XPro1595

EXPERIMENTAL

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

Drug: XPro1595

Interventions

XPro1595 DRUG

XPro1595 will be delivered by subcutaneous injection once a week

Also known as: INB03, DN-TNF, XENP345

0.3 mg/kg XPro1595; 0.6 mg/kg XPro1595; 1.0 mg/kg XPro1595

Eligibility Criteria

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

You may qualify if:

• Aged 18 years and above at screening;
• Diagnosed with probable AD defined by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria;
• Has hsCRP levels ≥1.5mg/L,OR HbA1c ≥ 6DCCT %, OR Erythrocyte Sedimentation Rate (ESR) ≥10 mm/h, OR APOE4 positive (at least one APOE4 allele);
• Female of childbearing potential (FCBP) must have confirmed negative urine pregnancy test at Screening;
• All female of childbearing potential (FCBP) and male patients who are sexually active with a female of childbearing potential must agree to use a highly effective contraception during the treatment period and until 90 days after the last dose of treatment for sexually active males whose partners are FCBP or until 30 days after the last dose of treatment for FCBP.
• Consents to having lumbar punctures;
• Consents to apolipoprotein E (APOE) genotyping(if status unknown);
• Provide written informed consent prior to any study procedures being performed;
• Has a caregiver who either lives in the same household or interacts withthe 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 behaviours and who canbe available to attend all clinic visits in personat which caregiver assessments are performed.Patients with caregivers that do not meet this criterionbut are determined by the investigator as able to provide an adequate assessment of the patient may also participate with prior approval from the sponsor.

You may not qualify if:

• Patients taking cholinesterase inhibitors, memantine, or antidepressant medication for less than 45 days from Day 1 (i.e. must be on stable dose for at least 45 days prior to Day 1);
• Have taken within the last 45 days from Day 1; 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 60 days from Day 1;
• Unable to tolerate lumbar puncture or taking medicine where lumber punctures are contraindicated (anti-coagulants besides daily 100mg of aspirin);
• A prior organ or stem cell transplant;
• A major adverse cardiac event within 6 months before screening;
• Lymphoma, leukaemia, or any malignancy within the past 5 years with the exception of malignancies with negligible risk of metastasis or death, such as 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;
• Unable to comply with the study procedures and assessments;12.Known hypersensitivity to investigational product or its excipients;

Sponsors & Collaborators

• Inmune Bio, Inc.: lead
• Alzheimer's Association: collaborator

Study Sites (5)

KaRa MINDS

Macquarie Park, New South Wales, 2113, Australia

Location

Mater Medical Research Institute

Brisbane, Queensland, 4101, Australia

Location

Central Adelaide Local Health Network

Woodville, South Australia, 5011, Australia

Location

Alfred Heath

Melbourne, Victoria, 3004, Australia

Location

Eastern Clinical Research Unit

Melbourne, Victoria, 3128, Australia

Location

Related Publications (4)

• McAlpine FE, Lee JK, Harms AS, Ruhn KA, Blurton-Jones M, Hong J, Das P, Golde TE, LaFerla FM, Oddo S, Blesch A, Tansey MG. Inhibition of soluble TNF signaling in a mouse model of Alzheimer's disease prevents pre-plaque amyloid-associated neuropathology. Neurobiol Dis. 2009 Apr;34(1):163-77. doi: 10.1016/j.nbd.2009.01.006.

  PMID: 19320056 RESULT

• Cavanagh C, Tse YC, Nguyen HB, Krantic S, Breitner JC, Quirion R, Wong TP. Inhibiting tumor necrosis factor-alpha before amyloidosis prevents synaptic deficits in an Alzheimer's disease model. Neurobiol Aging. 2016 Nov;47:41-49. doi: 10.1016/j.neurobiolaging.2016.07.009. Epub 2016 Jul 25.

  PMID: 27552480 RESULT

• Sama DM, Mohmmad Abdul H, Furman JL, Artiushin IA, Szymkowski DE, Scheff SW, Norris CM. Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats. PLoS One. 2012;7(5):e38170. doi: 10.1371/journal.pone.0038170. Epub 2012 May 29.

  PMID: 22666474 RESULT

• MacPherson KP, Sompol P, Kannarkat GT, Chang J, Sniffen L, Wildner ME, Norris CM, Tansey MG. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice. Neurobiol Dis. 2017 Jun;102:81-95. doi: 10.1016/j.nbd.2017.02.010. Epub 2017 Feb 24.

  PMID: 28237313 RESULT

Related Links

• Related Info
• Part the cloud grant information - Alzheimer's Association

MeSH Terms

Conditions

Alzheimer Disease; Inflammation

Interventions

XENP 1595

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Terrence O'Brien, MD

  The Alfred

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2019
• First Posted: May 9, 2019
• Study Start: November 20, 2019
• Primary Completion: June 30, 2021
• Study Completion: September 1, 2021
• Last Updated: June 15, 2023

Record last verified: 2023-06

Locations

AU (5)