Lomecel-B Effects on Alzheimer's Disease (CLEARMIND)

• ClinicalTrials.gov Identifier: NCT05233774
• Recruitment Status: Completed
• First Posted: February 10, 2022
• Last Update Posted: February 20, 2024
• Sponsor: Longeveron Inc.
• Collaborator: bioRASI, LLC
• Information provided by (Responsible Party): Longeveron Inc.

Tracking Information

• First Submitted Date: December 16, 2021
• First Posted Date: February 10, 2022
• Last Update Posted Date: February 20, 2024
• Actual Study Start Date: December 28, 2021
• Actual Primary Completion Date: September 29, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 31, 2022)

• Primary Endpoint 1: Safety - SAEs and AEs [ Time Frame: 41 weeks ]
  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.
• Primary Endpoint 2: Safety - Imaging [ Time Frame: 41 weeks ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 9, 2022)

• Secondary Endpoint 2: Efficacy- Change in the ADAS-cog-13 [ Time Frame: 41 weeks ]
  Change from baseline in the ADAS-cog-13 in Lomecel-B-treated arms versus change in placebo.
• Secondary Endpoint 3: Efficacy- Change in the MMSE [ Time Frame: 41 weeks ]
  Change from baseline in the MMSE in Lomecel-B-treated arms versus change in placebo.

Original Secondary Outcome Measures (submitted: January 31, 2022)

• Secondary Endpoint 2: Efficacy [ Time Frame: 41 weeks ]
  Change from baseline in the ADAS-cog-13 in Lomecel-B-treated arms versus change in placebo.
• Secondary Endpoint 3: Efficacy [ Time Frame: 41 weeks ]
  Change from baseline in the MMSE in Lomecel-B-treated arms versus change in placebo.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lomecel-B Effects on Alzheimer's Disease
• Official Title: Lomecel-B Effects on Alzheimer's Disease: A Randomized, Double-Blinded, Placebo-Controlled Phase 2a Trial
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study consists of 4 study arms of 12 patients each.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Mild Alzheimer's Disease

Intervention

• Drug: Allogeneic MSC
  An allogeneic bone marrow-derived medicinal signaling cell (MSC) formulation
• Other: Placebo
  Placebo

Study Arms

• Placebo Comparator: Placebo
  Group 1 will receive four infusions of Placebo on Day 0, Week 4, Week 8, and Week 12.
  Intervention: Other: Placebo
• Experimental: 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.
  Intervention: Drug: Allogeneic MSC
• Experimental: Lomecel-B Dose 2
  Group 3 will receive four infusions of 25M Lomecel-B on Day 0, Week 4, Week 8, and Week 12.
  Intervention: Drug: Allogeneic MSC
• Experimental: 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.
  Intervention: Drug: Allogeneic MSC

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 16, 2024): 50
• Original Estimated Enrollment (submitted: January 31, 2022): 48
• Actual Study Completion Date: September 29, 2023
• Actual Primary Completion Date: September 29, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05233774
• Other Study ID Numbers: 00-007-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Longeveron Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Longeveron Inc.
• Original Study Sponsor: Same as current
• Collaborators: bioRASI, LLC
• Investigators: Not Provided
• PRS Account: Longeveron Inc.
• Verification Date: February 2024