Lomecel-B Effects on Alzheimer's Disease

NCT05233774 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 00-007-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 13

Brief Summary

Dementia resulting from AD is associated with vascular function decline and involves a pro-inflammatory state. In our Phase 1 trial, Lomecel-B treatment met the primary safety endpoint, with no safety concerns, and showed potential to improve clinical assessments. Mechanistically, Lomecel-B treated subjects had higher serum concentrations of pro-vascular and anti-inflammatory biomarkers relative to placebo. This trial builds upon those preliminary Phase 1 results, and is designed to evaluate the safety profile of multiple infusions of Lomecel-B, and to investigate provisional efficacy of single dosing versus multiple dosing of Lomecel-B on cognitive function and biomarkers in AD subjects.

Conditions

Mild Alzheimer's Disease

Outcome Measures

Primary Outcomes (2)

• Primary Endpoint 1: Safety - SAEs and AEs

  To demonstrate that Lomecel-B infusions do not trigger the pre-specified stopping rules. Additional safety will be acquired throughout the study as follows: Incidence of all AEs and SAEs over the course of the trial.

  41 weeks

• Primary Endpoint 2: Safety - Imaging

  To demonstrate that Lomecel-B infusions do not trigger the pre-specified stopping rules. Additional safety will be acquired throughout the study as follows: Alzheimer's disease-related imaging abnormalities (ARIA) or clinically asymptomatic microhemorrhages as revealed by MRI.

  41 weeks

Secondary Outcomes (2)

• Secondary Endpoint 2: Efficacy- Change in the ADAS-cog-13

  41 weeks

• Secondary Endpoint 3: Efficacy- Change in the MMSE

  41 weeks

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Group 1 will receive four infusions of Placebo on Day 0, Week 4, Week 8, and Week 12.

Other: Placebo

Lomecel-B Dose 1

EXPERIMENTAL

Group 2 will receive an infusion of Lomecel-B at a dose of 25 x 10\^6 cells (25M) on Day 0, followed by Placebo infusions at Week 4, Week 8, and Week 12.

Drug: Allogeneic MSC

Lomecel-B Dose 2

EXPERIMENTAL

Group 3 will receive four infusions of 25M Lomecel-B on Day 0, Week 4, Week 8, and Week 12.

Drug: Allogeneic MSC

Lomecel-B Dose 3

EXPERIMENTAL

Group 4 will receive four infusions of Lomecel-B at a dose of 100 x 10\^6 cells (100M) on Day 0, Week 4, Week 8, and Week 12.

Drug: Allogeneic MSC

Interventions

Allogeneic MSC DRUG

An allogeneic bone marrow-derived medicinal signaling cell (MSC) formulation

Lomecel-B Dose 1; Lomecel-B Dose 2; Lomecel-B Dose 3

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent.
• Be 60 - 85 years of age at signing of the Informed Consent Form.
• Clinical diagnosis of mild Alzheimer's disease in accordance with the NIA-AA criteria at the time of enrollment.
• MMSE score of 19 - 23.
• Body weight of 40 - 150 kg.
• Has an adult caregiver who meets all of the following criteria.
• Provides written informed consent to participate on the trial (reporting on patient observations).
• Either lives with the patient, or sees the patient for at least 2 hours/day for at least 3 days/week.
• Is willing and able to participate in the study, and agrees to accompany the patient to each study visit.
• Is able to read, understand, and speak the designated language at the study site.
• Brain MRI consistent with AD.
• A PET scan using an FDA-approved tracer (e.g., AMYViD, Vizamyl, or Neuraceq) consistent with the diagnosis of AD. A prior positive PET scan will be allowed with Sponsor approval.
• Living in the community, includes assisted living facilities (but excluding long-term care nursing facilities).

You may not qualify if:

• Diagnosed with frontotemporal dementia (FTD), dementia due to Acquired Immunodeficiency Syndrome (AIDS), Creutzfeldt-Jakob disease (CJD), Lewy Bodies dementia (LBD), Progressive Supranuclear Palsy (PSP), multiple cerebral infarctions, or normal pressure hydrocephalus.
• Any other neurodegenerative disease.
• History of a seizure disorder.
• Evidence of: a prior macrohemorrhage; at least 4 cerebral microhemorrhages (regardless of anatomical location or diagnostic characterization as "possible" or "definite"); or at least 1 area of superficial siderosis.
• Unwillingness or inability to have MRIs scans (no contrasting agent will be used), or condition that contraindicates MRI, such as the presence metallic objects in the eyes, skin, or heart.
• Any conditions that contraindicates PET with a beta-amyloid tracer.
• Significant intestinal malabsorption surgery, e.g., gastric bypass.
• Serum B12 and/or folate levels below normal range.
• Clinically abnormal free T4 or thyroid-stimulating hormone (TSH).
• Resting blood oxygen saturation \<93%.
• Resting systolic blood pressure \>180 mm Hg, or diastolic blood pressure \>110 mm Hg.
• Regularly (\> 4 weeks) using high-doses of corticosteroids or other steroidal anti-inflammatory medication (e.g., Prednisone) on a regular basis, with the exception of steroidal nasal sprays, asthma inhalers, topical steroids, and hormonal-replacement therapy.
• Regularly (\> 4 weeks) using anti-cytokine antibody or targeting therapy, e.g., anti-TNF-α.
• Be an organ transplant recipient, or have active or expected future listing for any organ/tissue transplant while scheduled to be on trial, except for corneal, bone, skin, ligament, or tendon.
• Diagnosed with malignancy within the past 2 years, with the exception of curatively treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ, or cervical carcinoma.

Sponsors & Collaborators

• Longeveron Inc.: lead
• bioRASI, LLC: collaborator

Study Sites (13)

Visionary Investigators Network

Aventura, Florida, 33180, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Science Connections - Research Partner Group Multispecialty Group

Doral, Florida, 33178, United States

Location

Bruce W. Carter VA Medical Center

Miami, Florida, 33125, United States

Location

Miami Jewish Health

Miami, Florida, 33137, United States

Location

Allied Biomedical Research Institute

Miami, Florida, 33155, United States

Location

Ivetmar Medical Group

Miami, Florida, 33155, United States

Location

Fusion Medical Research and Clinic

Miami, Florida, 33173, United States

Location

First Excellent Research Group, LLC

Miami, Florida, 33175, United States

Location

Brainstorm Research

Miami, Florida, 33176, United States

Location

Miami Dade Medical Research Institute

Miami, Florida, 33176, United States

Location

Imic Inc.

Palmetto Bay, Florida, 33157, United States

Location

Brain Matters Research

Stuart, Florida, 34997, United States

Location

Related Publications (1)

• Rash BG, Ramdas KN, Agafonova N, Naioti E, McClain-Moss L, Zainul Z, Varnado B, Peterson K, Brown M, Leal T, Kopcho S, Carballosa R, Patel P, Brody M, Herskowitz B, Fuquay A, Rodriguez S, Jacobson AF, Leon R, Pfeffer M, Schwartzbard JB, Botbyl J, Oliva AA Jr, Hare JM. Allogeneic mesenchymal stem cell therapy with laromestrocel in mild Alzheimer's disease: a randomized controlled phase 2a trial. Nat Med. 2025 Apr;31(4):1257-1266. doi: 10.1038/s41591-025-03559-0. Epub 2025 Mar 10.

  PMID: 40065171 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of 4 study arms of 12 patients each.

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: February 10, 2022
• Study Start: December 28, 2021
• Primary Completion: September 29, 2023
• Study Completion: September 29, 2023
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)