Lomecel-B Effects on Alzheimer's Disease

NCT ID: NCT05233774

Last Updated: 2024-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-28
• Study Completion Date: 2023-09-29

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Lomecel-B Dose 1

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.

Group Type: EXPERIMENTAL

Allogeneic MSC

Intervention Type: DRUG

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

Lomecel-B Dose 2

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

Group Type: EXPERIMENTAL

Allogeneic MSC

Intervention Type: DRUG

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

Lomecel-B Dose 3

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.

Group Type: EXPERIMENTAL

Allogeneic MSC

Intervention Type: DRUG

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

Interventions

Allogeneic MSC

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

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

1. Provides written informed consent to participate on the trial (reporting on patient observations).

2. Either lives with the patient, or sees the patient for at least 2 hours/day for at least 3 days/week.

3. Is willing and able to participate in the study, and agrees to accompany the patient to each study visit.

4. 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).

Exclusion Criteria

• 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.
• Known hypersensitivity to dimethyl sulfoxide (DMSO).
• Test positive for hepatitis B virus surface antigen, viremic hepatitis C virus, HIV, or syphilis.
• Any condition that is projected to limited life expectancy to < 12 months.
• Be pregnant, nursing, or of childbearing potential while not practicing effective contraception.
• Be currently participating in any other investigational therapeutic or device trial, or have participated within one within the previous 30 days to screening, or in the opinion of the investigator, the patient should be excluded for such participation within the past 5 years.
• In the opinion of the investigator, the patient has any other illness or condition that: may compromise the participant's safety, compliance, or ability to successfully complete the study; may compromise the validity of the study; or otherwise should exclude the participant from enrollment.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

bioRASI, LLC

INDUSTRY

Sponsor Role: collaborator

Longeveron Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Visionary Investigators Network

Aventura, Florida, United States

Brain Matters Research

Delray Beach, Florida, United States

Science Connections - Research Partner Group Multispecialty Group

Doral, Florida, United States

Bruce W. Carter VA Medical Center

Miami, Florida, United States

Miami Jewish Health

Miami, Florida, United States

Allied Biomedical Research Institute

Miami, Florida, United States

Ivetmar Medical Group

Miami, Florida, United States

Fusion Medical Research and Clinic

Miami, Florida, United States

First Excellent Research Group, LLC

Miami, Florida, United States

Brainstorm Research

Miami, Florida, United States

Miami Dade Medical Research Institute

Miami, Florida, United States

Imic Inc.

Palmetto Bay, Florida, United States

Brain Matters Research

Stuart, Florida, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40065171 (View on PubMed)

Other Identifiers

00-007-01

Identifier Type: -

Identifier Source: org_study_id