Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans
ConditionHealthy Adults
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age23-90
SponsorMinicircle
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
Injectable Plasmid Klotho Gene Therapy
GeneticInjection of plasmid-delivered Klotho gene therapy
Treatment groups
24 Participants
are divided into 1 treatment groupGroup A: Schedule of Administration and Sample SelectionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Concentration of Serum α-Klotho Measured by Enzyme-Linked Immunosorbent Assay (pg/mL)
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.
Time frame
Measured 1 month before and 7 days before injection, then 3 days, 7 days, 1 month, 3 months, 6 months after2
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)
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.
Time frame
Measured 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.3
Concentration of Serum Fibroblast Growth Factor 23 (FGF23) Measured by Enzyme-Linked Immunosorbent Assay (pg/mL)
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.
Time frame
Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.4
Concentration of Intact Parathyroid Hormone Measured by Two-Site Immunoassay (pg/mL)
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.
Time frame
Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.Secondary outcomes
1
Change From Baseline in World Health Organization Quality of Life Brief Version Domain Scores (0-100)
The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) is a self-report questionnaire that includes four domains: Physical Health, Psychological, Social Relationships, and Environment. Each domain score is transformed to a 0-100 scale, with higher scores indicating better quality of life. Changes from baseline will be reported for each domain separately.
Time frame
Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 month, 6 months after.2
Change From Baseline in Flanker Inhibitory Control and Attention Test T-Score (Mean 50 ± 10)
The Flanker Inhibitory Control and Attention Test measures inhibitory control and attention. Scores are age-adjusted T-scores (mean 50, SD 10). Higher scores indicate better performance. Changes from baseline will be analyzed per participant and time point.
Time frame
Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.3
Change From Baseline in Dimensional Change Card Sort Test T-Score (Mean 50 ± 10)
The Dimensional Change Card Sort Test assesses cognitive flexibility. Scores are age-adjusted T-scores (mean 50, SD 10). Higher scores indicate better executive function. Changes from baseline will be analyzed per participant and time point.
Time frame
Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.4
Change From Baseline in Pattern Comparison Processing Speed Test T-Score (Mean 50 ± 10)
The Pattern Comparison Processing Speed Test measures processing speed using age-adjusted T-scores (mean 50, SD 10). Higher scores reflect faster cognitive processing. Changes from baseline will be analyzed per participant and time point.
Time frame
Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment. Source ClinicalTrials.gov