Evaluating the Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans: An Interventional, Non-Placebo-Controlled Pilot Phase Study
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 14
- 试验地点
- 4
- 主要终点
- Concentration of Serum α-Klotho Measured by Enzyme-Linked Immunosorbent Assay (pg/mL)
研究概览
简要总结
The purpose of this study is to investigate the safety and efficacy of a gene therapy for Klotho, delivered via a nonviral plasmid in healthy adult volunteers. Additionally, this study seeks to understand the cognitive and health benefits of the Klotho gene therapy.
详细描述
Note that the investigational product will be administered at a site outside of the U.S. which is not under FDA jurisdiction, and only non-treatment pre/post outcome assessments (e.g., cognitive assessments or blood sample collection) occur at the U.S. site.
Participants will take part in cognitive and health testing before and after administration of plasmid-delivered Klotho gene therapy. The method of administration will be subcutaneous injection into abdominal fat deposits. Klotho may improve cognitive function, kidney function, healthspan, and lifespan. Healthy volunteers will partake in a series of blood draws, health screenings, questionnaires, brain perfusion/function measures, and cognitive testing multiple times before and after the intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 23 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant is open to morphological change
- •If female, participant agrees to maintain contraception
- •If female, participant agrees to take a pregnancy test
- •If female, participant agrees to a pregnancy waiver
排除标准
- •Women of childbearing potential who are unwilling or unable to use effective contraception for the duration of the study
- •History of cancer diagnosis
- •Preexisting medical issues that may be exacerbated by the treatment
- •Has received any gene therapy within the past 12 months
- •Unwilling or unable to provide written informed consent
研究组 & 干预措施
Schedule of Administration and Sample Selection
This arm includes cognitive and health battery at multiple intervals pre- and post-administration of Klotho
干预措施: Injectable Plasmid Klotho Gene Therapy (Genetic)
结局指标
主要结局
Concentration of Serum α-Klotho Measured by Enzyme-Linked Immunosorbent Assay (pg/mL)
时间窗: Measured 1 month before and 7 days before injection, then 3 days, 7 days, 1 month, 3 months, 6 months after
Serum α-Klotho protein concentration will be quantified using a validated enzyme-linked immunosorbent assay (ELISA). Results will be reported as picograms per milliliter (pg/mL) for each participant at each time point. Higher or lower values have no inherent directionality and will be interpreted in study context.
Adverse Events: Number and Percentage of Participants Experiencing Treatment-Emergent Adverse Events as Assessed Patient-Reported Outcomes Version of Common Terminology Criteria for Adverse Events (PRO-CTCAE)
时间窗: Measured 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Assessed through a checklist version of the PRO-CTCAE with each symptom options being none, mild, moderate, or severe. Items will be scored with 0, 1, 2, 3 respectively. Item responses will be summarized as number and percentage of participants experiencing each adverse event by system/organ class. High scores indicate highest severity of symptoms and low scores indicate no symptoms.
Concentration of Serum Fibroblast Growth Factor 23 (FGF23) Measured by Enzyme-Linked Immunosorbent Assay (pg/mL)
时间窗: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Fibroblast Growth Factor 23 (FGF23) concentration will be quantified in serum using a validated enzyme-linked immunosorbent assay (ELISA). Results will be expressed in picograms per milliliter (pg/mL) for each participant and time point. FGF23 is a downstream effector of α-Klotho signaling and reflects activity of the phosphate-vitamin D regulatory axis.
Concentration of Intact Parathyroid Hormone Measured by Two-Site Immunoassay (pg/mL)
时间窗: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Intact Parathyroid Hormone (PTH) will be measured in serum using a two-site immunoassay that detects the full-length molecule. Results will be reported in picograms per milliliter (pg/mL) per participant and time point. PTH reflects parathyroid activity within the α-Klotho-FGF23-vitamin D feedback pathway.
Concentration of Serum 1,25-Dihydroxyvitamin D (Calcitriol) Measured by Liquid Chromatography-Tandem Mass Spectrometry (pg/mL)
时间窗: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Serum 1,25-dihydroxyvitamin D (calcitriol) will be quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Concentrations will be expressed in picograms per milliliter (pg/mL). This hormone regulates calcium and phosphate balance and is a downstream marker of α-Klotho-FGF23-PTH axis modulation.
Concentration of Serum Phosphorus Measured by Clinical Chemistry Analyzer (mg/dL)
时间窗: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Serum inorganic phosphorus will be measured on a standard clinical chemistry analyzer. Results will be reported in milligrams per deciliter (mg/dL) for each participant and time point. Phosphorus levels reflect systemic phosphate homeostasis influenced by α-Klotho and FGF23 activity.
Urinary Phosphate Excretion Measured by Clinical Chemistry Assay (mg/24 h or mg/g Creatinine)
时间窗: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Urinary phosphate will be assessed using a validated chemistry assay. Results will be expressed either as total phosphate excretion in milligrams per 24 hours (mg/24 h) or as the phosphate-to-creatinine ratio (mg phosphate per g creatinine). This measure reflects renal handling of phosphate and functional effects of α-Klotho on phosphate excretion.
Concentration of Serum Cystatin C Measured by Immunoassay (mg/L)
时间窗: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Serum Cystatin C will be measured using a standardized immunoassay and reported in milligrams per liter (mg/L) for each participant and time point. Cystatin C serves as a biomarker of glomerular filtration rate and provides a mechanistic link between α-Klotho activity and renal function.
次要结局
- Concentration of Serum Bicarbonate (CO₂) Measured by Clinical Chemistry Analyzer (mmol/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Change From Baseline in World Health Organization Quality of Life Brief Version Domain Scores (0-100)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 month, 6 months after.)
- Change From Baseline in Flanker Inhibitory Control and Attention Test T-Score (Mean 50 ± 10)(Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.)
- Change From Baseline in Dimensional Change Card Sort Test T-Score (Mean 50 ± 10)(Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.)
- Change From Baseline in Pattern Comparison Processing Speed Test T-Score (Mean 50 ± 10)(Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.)
- Change From Baseline in Picture Sequence Memory Test T-Score, Forms A and B (Mean 50 ± 10)(Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.)
- Change From Baseline in Picture Vocabulary Test T-Score (Mean 50 ± 10)(Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.)
- Change From Baseline in Reynolds Intellectual Assessment Scales-Second Edition (RIAS-2) Composite Scores (Standard Score Mean 100 ± 15)(Measured 1 month before and then 1 month and 3 months after.)
- Concentration of Serum Glucose Measured by Clinical Chemistry Analyzer (mg/dL)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Total Serum Calcium Measured by Clinical Chemistry Analyzer (mg/dL)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Ionized Calcium Measured by Ion-Selective Electrode (mmol/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Serum Sodium Measured by Ion-Selective Electrode (mmol/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Serum Potassium Measured by Ion-Selective Electrode (mmol/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Serum Chloride Measured by Ion-Selective Electrode (mmol/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Blood Urea Nitrogen (BUN) Measured by Clinical Chemistry Analyzer (mg/dL)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Serum Creatinine Measured by Clinical Chemistry Analyzer (mg/dL)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Serum Albumin Measured by Clinical Chemistry Analyzer (g/dL)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Total Serum Protein Measured by Biuret Method (g/dL)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Alkaline Phosphatase (ALP) Measured by Clinical Chemistry Analyzer (IU/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Alanine Aminotransferase (ALT) Measured by Clinical Chemistry Analyzer (IU/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Aspartate Aminotransferase (AST) Measured by Clinical Chemistry Analyzer (IU/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Total Serum Bilirubin Measured by Diazo Method (mg/dL)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of High-Sensitivity C-Reactive Protein (hs-CRP) Measured by Immunoturbidimetric Assay (mg/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Asymmetric Dimethylarginine (ADMA) Measured by Liquid Chromatography-Tandem Mass Spectrometry (µmol/L)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Concentration of Platelet Factor 4 (PF4) Measured by Enzyme-Linked Immunosorbent Assay (ng/mL or OD Units)(Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.)
- Epigenetic Biological Age Estimated From Whole-Genome DNA Methylation Profiles (years)(Measured 7 days before administration and then 3 days, 7 days, 1 month, 3 months, and 6 months after administration)
- Estimated Brain Age: Derived From Kernel Flow Functional Near-Infrared Spectroscopy (fNIRS) Analysis (years)(Measured 7 days before and then 3 days, 7 days, 1 month, and 3 months after treatment)
- Cognitive Performance Index and Domain Percentiles Derived From Kernel Flow functional near-infrared spectroscopy (fNIRS) and Behavioral Metrics (percentile where higher = better)(Measured 7 days before and then 3 days, 7 days, 1 month, and 3 months after treatment)