NCT05233774已完成2 期
Lomecel-B Effects on Alzheimer's Disease: A Randomized, Double-Blinded, Placebo-Controlled Phase 2a Trial
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 12
- 主要终点
- Primary Endpoint 1: Safety - SAEs and AEs
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 -
- •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).
排除标准
- •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.
研究组 & 干预措施
Placebo
Placebo Comparator
Group 1 will receive four infusions of Placebo on Day 0, Week 4, Week 8, and Week 12.
干预措施: Placebo (Other)
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.
干预措施: Allogeneic MSC (Drug)
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.
干预措施: Allogeneic MSC (Drug)
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.
干预措施: Allogeneic MSC (Drug)
结局指标
主要结局
Primary Endpoint 1: Safety - SAEs and AEs
时间窗: 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
时间窗: 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.
次要结局
- Secondary Endpoint 2: Efficacy- Change in the ADAS-cog-13(41 weeks)
- Secondary Endpoint 3: Efficacy- Change in the MMSE(41 weeks)
研究者
研究点 (12)
Loading locations...
相似试验
招募中
不适用
Study on the Relationship Between Peripheral Blood miRNA and Risk and Severity of Alzheimer's DiseaseAlzheimer DiseaseMicroRNAsNCT06442852Jiajie Chen500
Unknown
不适用
Retinal Neuro-vascular Coupling in Patients With Neurodegenerative DiseaseMild Cognitive ImpairmentAlzheimer DiseaseHealthyNCT02663531Medical University of Vienna150
Unknown
不适用
Modulation of Cognition and Brain Connectivity by Noninvasive Brain Stimulation in Patients With Mild Cognitive Impairment Due to Alzheimer's DiseaseMild Cognitive ImpairmentNCT04012346Masaryk University20
已完成
3 期
Effect of LY2062430 on the Progression of Alzheimer's DiseaseAlzheimer's DiseaseNCT00905372Eli Lilly and Company1,000
已完成
不适用
Cerebrovascular dysfunction in Alzheimer and mild cognitive impairment.cerebrovasculaire dysfunctiealzheimermild cognitive impairment1002930510047066dementiaNL-OMON30568Academisch Ziekenhuis Maastricht60
相关资讯
Alzheimer's Disease: Cell and Gene Therapy Advances in 2024- Lexeo Therapeutics' LX1001 gene therapy shows dose-dependent APOE2 expression increase and reduced tau biomarkers in APOE4 homozygote Alzheimer's patients.
- Lomecel-B cell therapy demonstrates safety and potential cognitive benefits in mild Alzheimer's patients, according to Phase 2a CLEAR MIND trial data.
- NKGen Biotech advances SNK01 natural killer cell therapy to Phase 2 after promising Phase 1 results, including cognitive function improvements.
- Regeneration Biomedical doses first patient in Phase 1 trial of RB-ADSC, an autologous stem cell therapy for Alzheimer's, showing no adverse events.last yearCell and Gene Therapies Emerge as Promising Avenues for Alzheimer's Disease Treatment• Several cell and gene therapies are under investigation for Alzheimer's disease, with some showing early signs of efficacy in clinical trials.
• NKGen's SNK01, an autologous NK cell therapy, demonstrated encouraging clinical activity and tolerability in a Phase 1 trial, with improvements in ADCOMS scores and CSF α-syn levels.
• Longeveron's Lomecel-B, an allogeneic MSC therapy, showed statistically significant improvements in ADCS-ADL scores and trends of improvement on MMSE in a Phase 2 trial.
• Beyond amyloid-targeting antibodies, researchers are exploring diverse targets like tau, inflammation, and viral proteins, with drug repurposing strategies also gaining traction.last yearLomecel-B Shows Promise in Phase IIa Alzheimer's Trial- Lomecel-B demonstrated a slowing of disease worsening compared to placebo in a Phase IIa clinical trial for mild Alzheimer's Disease, marking a potential advancement in treatment.
- The trial data indicated that Lomecel-B has a strong safety profile, with no incidence of hypersensitivity or infusion-related reactions observed in both single and multiple dosing.
- Significant improvements were seen in the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scale, suggesting a positive impact on patients' daily functions.
- Lomecel-B minimized brain volume loss in key areas affected by Alzheimer's, including the hippocampus, with statistically significant results for left hippocampal volume relative to placebo.2 years ago