PIEZO-101 First-in-Human Safety and Proof-of-Concept Study

An Open-Label, Within Participant-Controlled, First-in-Human (FIH) Study to Explore the Safety, Tolerability, and Pharmacodynamic Effects of PIEZO-101, an Investigational Plasmid DNA Biostimulator Delivered by Intradermal Electroporation to the Knee and Décolleté Regions in Healthy Adult Female Participants

The aim of this first-in-human clinical study is to explore the safety, tolerability, pharmacodynamics, and exploratory efficacy of PIEZO-101, an investigational plasmid DNA biostimulator that aims to restore expression of key proteins in the skin for extracellular matrix rejuvenation. PIEZO-101 is administered using an intradermal injection followed by localized electroporation using the investigational device Piezopen. This clinical trial will study safety and tolerability, pharmacodynamics using biopsies from the left knee, and exploratory efficacy using photography on the décolleté. Up to 8 participants may be enrolled to ensure 6 evaluable participants complete the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Skin Aging; Décolleté Wrinkles; Wrinkles in Decolletage; Wrinkles in Left Knee; Left Knee Skin Laxity
• Intervention / Treatment: Biological: PIEZO-101; Device: Piezopen; Other: Sterile Saline (0.9% NaCl)

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria (Participants must meet ALL of the following criteria to be eligible for enrollment):

1. Healthy female adults aged 40-65 years
2. Fitzpatrick skin phototype score I-IV
3. Visible signs of skin laxity, wrinkling, or crepiness in the knee area, confirmed by photographic documentation reviewed by at least two independent assessors
4. Visible signs of wrinkling or crepiness in the décolleté area suitable for standardized photography, free of tattoos, significant scarring, or confounding skin conditions in the photography field, confirmed by photographic documentation reviewed by at least two independent assessors
5. Willingness to undergo all protocol-required skin punch biopsies (four at Day 7 and four at Day 35) from the knee area
6. Willingness to abstain from other aesthetic or dermatologic treatments in the knee and décolleté areas during the study
7. For women of childbearing potential (WOCBP): commitment to use a highly effective method of contraception (combined hormonal contraception, progestogen-only contraception, intrauterine device or hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence) from the Screening Visit through the Day 90 End-of-Study visit. Postmenopausal status, defined as ≥12 months of natural amenorrhea, is not considered childbearing potential.
8. Negative serum β-hCG pregnancy test at the Screening Visit (Visit 1) and negative urine pregnancy test at the treatment visits (Visit 2 and Visit 6) prior to dose for participants of child-bearing potential
9. Willing and able to comply with all scheduled visits (10 study site visits), treatment plan, and study procedures for the full 90-day study duration
10. Able to understand and willing to sign a written informed consent document.

Exclusion Criteria (Participants must meet NONE of the following criteria to be eligible for enrollment):

1. History of keloid or hypertrophic scarring
2. Known allergy or hypersensitivity to any antibiotic
3. Known hypersensitivity to lidocaine, prilocaine, or any component of the topical anesthetic preparation
4. Active dermatologic conditions or infections (such as psoriasis, eczema, active acne, or dermatitis) in the knee or décolleté treatment areas
5. History of knee surgery or significant scarring in the knee treatment area; history of breast augmentation, reduction, or surgery resulting in scarring in the décolleté treatment area
6. Use of systemic corticosteroids, immunosuppressants, or medications affecting wound healing within 30 days of Day 0
7. Known autoimmune disease or immunodeficiency
8. Pregnancy or breastfeeding
9. Participation in another investigational study within 30 days of Day 0
10. Known allergy to metals such as stainless steel
11. Prior gene therapy of any kind (for clarity, prior receipt of RNA and DNA vaccines is not exclusionary)
12. Implanted electronic device (e.g., cardiac pacemaker, defibrillator, neurostimulator)
13. Any aesthetic procedure (injectable, energy-based device, laser, filler, biostimulator, chemical peel, topical prescription product) in the knee or décolleté areas within 6 months of screening
14. Tattoos, permanent makeup, or scarring in the knee or décolleté treatment areas that could interfere with clinical or photographic assessments
15. History of any malignancy within 5 years prior to screening, except adequately treated basal cell or squamous cell carcinoma of the skin outside the treatment areas
16. Any condition that, in the opinion of the PI, would compromise participant safety or study integrity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; Four intradermal injections of PIEZO-101 at Dose Level 1 followed by Piezopen application in the left knee and décolleté each, along with four injections of saline control (intra-participant comparator) in the left knee. Administered on Day 0 and Day 28.	Biological: PIEZO-101; Plasmid DNA biostimulator; Device: Piezopen; Intradermal electroporation device; Other: Sterile Saline (0.9% NaCl); Intra-participant comparator (control)
Experimental: Dose Level 2; Four intradermal injections of PIEZO-101 at Dose Level 2 followed by Piezopen application in the left knee and décolleté each, along with four injections of saline control (intra-participant comparator) in the left knee. Administered on Day 0 and Day 28.	Biological: PIEZO-101; Plasmid DNA biostimulator; Device: Piezopen; Intradermal electroporation device; Other: Sterile Saline (0.9% NaCl); Intra-participant comparator (control)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of intradermal delivery of PIEZO-101 followed by Piezopen EP	Described via Common Terminology Criteria for Adverse Events (CTCAE) v6.0 through Day 90, including clinical laboratory assessments (hematology, serum chemistry, inflammatory markers) and vital signs	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize local tissue responses in treatment (PIEZO-101 + Piezopen EP) and control (saline) sites	Scoring to characterize tissue responses such as erythema, edema, bruising, induration, pain, and itching after treatment application	Up to 3 months
Describe Piezopen EP procedural tolerability	Scoring to describe pain level of procedure	Up to 3 months
Explore transgene mRNA expression 7 days after each dose	Characterization of PIEZO-101-treated biopsy versus saline-treated biopsy via qPCR assay	Up to 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe protein-level pharmacodynamic evidence in biopsy specimens from treated vs control sites	Characterization of PIEZO-101 and saline groups for extracellular matrix protein expression via immunofluorescence and histological changes using standardized stains, performed on respective biopsies	Up to 3 months
Explore aesthetic improvements over time	Characterization of changes in skin quality and wrinkle severity over time relative to baseline using GAIS scale, scored by blinded independent assessor and participant self-assessment	Up to 3 months
Describe anti-drug antibody (ADA) immunogenicity	Explore whether PIEZO-101 with Piezopen EP elicits any anti-drug antibody responses in participants using ELISA	Up to 3 months

Collaborators and Investigators

• Sponsor: Piezo Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: June 22, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Skin aging; First-in-human; Skin rejuvenation; Plasmid DNA; Biostimulator; Decolette wrinkles; Knee skin laxity; Intradermal electroporation; Extracellular matrix regeneration
• Other Study ID Numbers: PIEZO-101-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No