This study is a phase 1/2 clinical trial to evaluate the safety and efficacy of administering clusters of autologous dermal fibroblasts to subjects with periorbital wrinkles on both sides.
If subjects who have signed the Informed consent form voluntarily are enrolled in this study, they will be tested for eligibility during the screening period. Subjects will visit the study site a total of 6 times while participating in this study. The subjects who meet the inclusion/exclusion criteria will receive a total of one dose of the IP (Visit 3). Then, the efficacy evaluation will be conducted at Visit 4 (Week 2), Visit 5 (Week 12), and Visit 6 (Week 24), and safety will also be evaluated at each visit.

Treatment

Subjects are randomly assigned to either the test group or the placebo group according to the registered order.
The test drug or placebo will be injected once intradermally.
 - Test Drug : Sterilized nutrient solution containing 1.0x10^7 cells of autologous fibroblast/1 mL vial
 - Placebo : Sterilized nutrient solution/1 mL vial 
 - Administration site: Periorbital wrinkle area
 - Dosage: Administer one 1 mL vial to the periorbital wrinkle area.

Arm Label

Target Number of Participant

Arm Type

Arm Description

Dose: Clusters of autologous dermal fibroblast 1x10^7 cells/1 mL/vial

Arm Label

Target Number of Participant

Arm Type

Arm Description

Up to 1 mL of the placebo is administered intradermally.

Gender

Age

Description

1) Participants of ages 19 and older
2) Those with at least 3 points (Moderate) of the IGA-LCL severity scale on both sides in the rest state during screening
3) Those who have visually symmetrical periorbital wrinkles on both sides and have the same IGA-LCL severity scale score in the rest state
4) Those who agreed to discontinue all dermatological treatments including facial wrinkle improvement during this study period
5) Subjects with healthy and undamaged skin at the sampling area (e.g., behind the ears, inside of the arms, armpits, groin, etc.)    
6) Those who meet the following criteria based on the blood test at screening or baseline visits
  - White Blood Cell : ≥4.5x10^3/μl and ≤11.0x10^3/μl
  - Platelet count : ≥100x10^3/μl
  - Hemoglobin : ≥9 g/dL
7) Those who sign the written consent form after hearing the explanation of the purpose, method, and efficacy of this study
8) Those who can be followed up during the study period

1)  Those with arterial bleeding or severe variceal bleeding in the body
2)  Those with hypersensitivity to bovine protein or gentamicin
3)  Pregnant and breast-feeding  or who planning to conceive within six months of clinical trial medication
4)  Out of who are pregnant or breast-feeding and A woman who is likely to be pregnant in a postmenopausal or a state of non-Infertility  surgery and men with reproductive abilities not willing or planning to use the appropriate contraception defined in this clinical trial during their participation in clinical trials
5)   Those with or suspected of having autoimmune diseases (e.g., myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, etc.)
6)  At the screening visit, patients with chronic skin disease or such a medical history 
7)  Those with a medical history or a positive test result for any of the following: hepatitis C virus antibody (HCV Ab), hepatitis B surface antigen (HBsAg), human immunodeficiency virus-1 (HIV-1) antibody, human immunodeficiency virus-2 (HIV-2) antibody
   (However, if HCV is proven to be completely cured based on the HCV RNA test, he/she can be enrolled as a subject.)
8)   Those with severe heart diseases (e.g., myocardial infarction, heart failure, etc.) or severe liver diseases (e.g., hepatocirrhosis, liver failure, etc.) or severe kidney diseases (e.g., renal failure, etc.)
9)  Those who have tumors or have such medical history within 5 years of screening
 (However, if the malignant tumor does not relapse for more than 5 years, the candidate may be enrolled as a subject, and in the case of basal cell carcinoma or intradermal squamous cell carcinoma that does not relapse after resection, he/she can be enrolled as a subject.)
10)   Those with genetic diseases affecting fibroblast or collagen
11) Those who have undergone anticoagulant therapy or antiplatelet therapy within 10 days prior to administration of the study drug, or those who are expected to need to receive them within 3 days after administration of the study drug
   (However, if the drug is being administered at the time of screening, it is possible to participate in the clinical trial after a seven-day not administering medication period only if the temporary suspension does not pose a medical risk under the tester's judgment, tried tissue biopsy Schedule.)
12)  Those who have active or infectious skin diseases (skin infection, inflammation, herpes, etc.), keloids, unhealed wounds or scars, tumors, etc. at the site where the study drug will be administered, or those who have previously received radiation treatment
13)  Those with hypersensitivity to local anesthetics (however, those who agree to receive the procedure without applying an anesthetic agent due to hypersensitivity to local anesthetics, do not fall under this criteria.)
14)  A person who has a history of significant adverse or hypersensitive reactions to the composition of medications for clinical trials
15)  Those who have undergone procedures that can affect periorbital wrinkles, such as dermabrasion, skin regeneration, and plastic surgery, etc, among facial procedures including the eye area* or those who are expected to have such procedures during the study period
16)  Those who participated in another study and received an investigational drug or used an investigational medical device within 6 months prior to participation in this study, or those who are scheduled to participate in another study during this study period
17)  Those with a medical history of autologous dermal fibroblast treatment
18)  Those with a medical history of anaphylaxis or severe complex allergies
19)  Those with a medical history of keloid formation, hyperpigmentation, or hypertrophic scars on the face
20)  Those who have clinically serious disorders in the cardiovascular system, digestive system, respiratory system, endocrine system, or central nervous system, or have had or currently have a mental disorder that significantly affects this study
21)  Those who received systemic corticosteroid within 12 weeks prior to participation in this study
22)  Those who refuse to take pictures of the site where the study drug is administered
23)  Those who are judged to be ineligible by the investigator to participate in this study for other reasons

Percentage of Improvement in IGA-LCL Wrinkle Severity at Rest stage in 2 score or higher

12 weeks after administration

Percentage of Improvement in IGA-LCL Wrinkle Severity at Rest stage in 2 score or higher

24 weeks after administration

Percentage of Improvement in IGA-LCL Wrinkle Severity at Rest stage in 1 score or higher

12 weeks and 24 weeks after administration

Percentage of Improvement in FWS-A

12 weeks and 24 weeks after administration

Changes rate of FWS-A score

12 weeks and 24 weeks after administration

Changes rate of GAIS score

12 weeks and 24 weeks after administration

Changes rate of PRIMOS®Lite score

12 weeks and 24 weeks after administration

Adverse Events

Screening (~9 weeks,-8 weeks-1 weeks), base line (day0), 2 weeks, 12 weeks and 24 weeks after administration

Laboratory Tests

Screening (~9 weeks), base line (day0), 2 weeks, 12 weeks and 24 weeks after administration

Vital Signs

Screening (~9 weeks,-8 weeks-1 weeks), base line (day0), 2 weeks, 12 weeks and 24 weeks after administration

Physical Examination

Screening (~9 weeks,-8 weeks-1 weeks), base line (day0), 2 weeks, 12 weeks and 24 weeks after administration