Safety Assessment of Leronlimab and Its Effect on Brain Inflammation in Alzheimer's Disease

NCT07553338 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-09027933
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The present study will administer the drug leronlimab to 20 participants who are above 50 years old with Alzheimer's disease (AD) or mild cognitive impairment due to AD. While leronlimab is considered safe in other diseases like Human Immunodeficiency Virus (HIV) and certain types of breast cancer, its safety and tolerability in AD will be tested for the first time. The main purpose of this study is to learn:

1. 1.Is this drug safe for participants with AD and MCI due to AD?
2. 2.Does leronlimab change levels of brain inflammation?
3. 3.Undergo 2 types of brain scans, Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI).
4. 4.Visit our clinic for routine lab work, an electrocardiogram (ECG), and a physical exam.
5. 5.Donate blood so the researchers can better understand how leronlimab affects levels of inflammation and proteins related AD in the blood.
6. 6.Undergo a series of tests and questionnaires that test thinking abilities.
7. 7.Have weekly phone calls with researchers to let them know if there are side effects will taking this drug.

Conditions

Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease; Alzheimer's Disease

Keywords

Alzheimer's Disease; Mild Cognitive Impairment; Clinical Trial

Outcome Measures

Primary Outcomes (1)

• Mean change from baseline in whole-brain inflammation using 11C-DPA-713 Positron Emission Tomography (PET)

  The primary outcome measure is leronlimab's effect on brain inflammation using a PET tracer that measures translocator protein (TSPO) activation on microglia.

  Baseline; Week 13

Secondary Outcomes (2)

• Number and severity of treatment-emergent adverse events (TEAEs)

  Baseline through Week 17

• Number of serious adverse events (SAEs)

  Baseline through Week 17

Study Arms (1)

Single arm

OTHER

All participants (N = 20) enrolled into this phase 2a, single-arm study will receive 12 doses of leronlimab.

Drug: Leronlimab (700mg)

Interventions

Leronlimab (700mg) DRUG

Leronlimab, also known as PRO 140, is a humanized IgG4κ monoclonal antibody to Chemokine Receptor type 5 (CCR5). It is currently in development to potentially treat a number of different diseases, including but not limited to, Human Immunodeficiency Virus (HIV) and various oncological conditions.

Single arm

Eligibility Criteria

• Age: 50 Years+
• Gender Eligibility Details: Cisgender Males and Cisgender Females
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Potential participants are required to meet all the following criteria for enrollment into the study:
• Adult males or females, 50 years of age and older
• Biomarker confirmed mild-to-moderate i.e., mild cognitive impairment/AD (MCI/AD) based on standard criteria (CDR 0.5 to 1.5).
• Cognition intact enough to participate in study procedures including cognitive testing (MoCA\>11)
• Clinically normal resting 12-lead ECG at screening or, if abnormal, considered not clinically significant by the investigator
• Participant (or legally authorized representative) provides written informed consent prior to initiation of any study procedures
• Understands and agrees to comply with planned study procedures
• If receiving an FDA approved drug that treat the symptoms of AD (e.g., cholinesterase inhibitors and/or memantine) must be on a stable dose for at least 12 weeks prior to baseline
• If receiving an FDA approved drug that targets brain amyloid must be on a stable dose for at least 12 weeks prior to baseline
• If the participant is taking any supplement or medical food that may affect brain function must be on a stable dose or regimen for at least 12 weeks prior to baseline
• Participants on permitted concomitant medications should be on a stable dose of the permitted concomitant medication for at least 4 weeks unless a shorter duration is deemed acceptable by the investigator
• In the opinion of the investigator have adequate cognition, literacy, vision, and hearing for neuropsychological testing
• The participant should have a study partner who can support the study participant and provide collateral information.

You may not qualify if:

• Potential participants meeting any of the following criteria will be excluded from enrolment into the study:
• Participant with a gene variation that would inhibit binding to the PET radiotracer (11C-DPA-713) and/or clinical factors that could affect PET signal, such as chronic use of benzodiazepines or NSAIDS
• Women who are pregnant or breastfeeding at screening or baseline
• Females of childbearing potential who within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following: (1) total abstinence, if it is their preferred and usual lifestyle; (2) an intrauterine device or intrauterine hormone-releasing system; (3) a contraceptive implant; (4) an oral contraceptive (with additional barrier method) with the participant being on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation; (5) have a vasectomized partner with confirmed azoospermia. Women who do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation shall be excluded. However, at the discretion of the investigator it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the subject, then the subject must agree to use a medically acceptable method of contraception, i.e., double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide. NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
• Male participants with female partners of childbearing potential are not eligible to participate if they do not agree to ONE of the following from the time prior to first dosing until 90 days after the last dose of study treatment: (1) are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; (2) Agree to use a male condom plus partner use of a contraceptive method with a failure rate of \<1% per year when having penile-vaginal intercourse with a partner of childbearing potential who is not currently pregnant. Men with a pregnant or breastfeeding partner are not eligible to participate if they do not agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration from the time prior to first dosing until 90 days after the last dose of study treatment
• Participants who are HIV positive at screening
• Participants with a past history (suspected or confirmed) of Hepatitis B should have HBsAg testing at screening and are excluded if HBsAg is positive
• Participants with a past history (suspected or confirmed) of Hepatitis C should have HCV RNA PCR testing at screening and are excluded if the HCV RNA PCR test is positive
• Presence based on exam, history or MRI of significant brain disease other than AD such as schizophrenia, epilepsy, Parkinson's disease or large territory stroke
• Current substance abuse in accord with Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) criteria
• Significantly depressed (Geriatric Depression Scale \> 10)
• Contraindications to MRI scanning, including claustrophobia, cardiac pacemaker/defibrillator, ferromagnetic metal implants (e.g., in skull and cardiac devices other than those approved as safe for use in MRI scanners)
• Contraindications to PET
• Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG at screening or baseline which in the opinion of the investigator require further investigation or treatment or which may interfere with study procedures or safety
• Any other medical conditions (e.g., cardiac, respiratory, gastrointestinal, or renal) which are not stable and/or adequately controlled, or which in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• William H. Donner Foundation: collaborator

Study Sites (1)

Weill Cornell Medicine Brain Health Imaging Institute

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

leronlimab

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Tracy A Butler, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edward Spector, BS

CONTACT

6469628506; ejs4002@med.cornell.edu

Alexus A. Jones, BS

CONTACT

646-962-4994; ALJ4006@med.cornell.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The present study is a Phase 2a, single arm, open label, proof of principle study to evaluate the PET-measured effect on brain inflammation and safety of leronlimab in people with biomarker confirmed mild-to-moderate i.e., mild cognitive impairment/AD

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 28, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)