Effectiveness and Safety Comparison of Lunaphil Ultra (Hyaluronic Acid, by Espad Pharmed Co.) Versus Juvederm Ultra 4® (Hyaluronic Acid, by Allergan Co.) in Nasolabial Folds (NLFs) Management

A Randomized, Double-masked, Active Controlled, Within-subject Equivalency Clinical Trial to Compare Effectiveness and Safety of Lunaphil Ultra (Hyaluronic Acid, Produced by Espad Pharmed Co.) Versus Juvederm Ultra 4® (Hyaluronic Acid, Produced by Allergan Co.) for the Management of Moderate or Severe Nasolabial Folds

Rationale and background: Skin aging is a complex process that results in various changes in the skin, including wrinkles, sun spots, and sagging skin. The NLF is a natural change that becomes more prominent with aging and significantly affects the beauty of the facial skin. Dermal fillers, particularly hyaluronic acid (HA) fillers, are commonly used to correct these signs of aging. This study aimed to compare the effectiveness and safety of Lunaphil Ultra with Juvederm Ultra 4® for treating NLFs.

Primary objective: Effectiveness assessment of Lunaphil Ultra Secondary objectives: Effectiveness and safety assessment of Lunaphil Ultra Study design: This is a randomized, double-masked, active controlled, within-subject, and equivalency clinical trial.

Setting: Subjects were treated with Lunaphil Ultra in one NLF and Juvederm Ultra 4® in the opposite NLF.

Study Overview

• Status: Completed
• Conditions: Moderate or Severe Nasolabial Folds
• Intervention / Treatment: Device: Hyaluronic acid Lunaphil Ultra (by Espad Pharmed Co.); Device: Hyaluronic acid Juvederm Ultra 4® (by Allergan Co.)

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Iran
  • Tehran, Iran, 19947-66411
    • Orchid Pharmed, Medical Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects ≥ 30 years of age
• Visible bilateral NLFs that were approximately symmetrical and had an equal severity ranging from moderate to severe (assessed at the deepest part)
• Able to follow study instructions and likely to complete all required visits
• Signed informed consent

Exclusion Criteria:

• History of bleeding disorders or participants receiving or recently exposed (≤ 3 weeks) to continuous treatment with thrombolytics, anticoagulants, platelet inhibitors, or NSAIDs
• Acute herpetic eruption
• Known susceptibility to keloid formation, hypertrophic scarring or clinically significant skin pigmentation disorders
• Known sensitivity to local anesthetics of the amide type (such as lidocaine), history of hypersensitivity to gram-positive bacterial proteins, history of multiple severe allergies, history of anaphylactic shock
• Known hypersensitivity to any component of the study products or excipients (like hyaluronic acid)
• History of receiving immune therapy or a history of autoimmune disease
• History of active chronic debilitating systemic disease
• History of connective tissue disease, history of malignancy (except for non-melanoma skin cancer) within the last 5 years
• Clinically significant active dermatologic disorders within the last 6 months
• Use of oral retinoids, over-the-counter (OTC) or prescription antiwrinkle treatments, microdermabrasion, or chemical peels in the NLF area within the last 4 weeks or intention to use them during the study
• Any prior cosmetic procedure or tissue augmentation at the NLF injection site within 1 year before study entry (or intent to undergo such a procedure during the study)
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lunaphil Ultra (by Espad Pharmed Co.); Lunaphil Ultra (by Espad Pharmed Co.) will be administered over a 2-week period (initial treatment plus one touch-up) to achieve optimal correction of the NLFs. In case of suboptimal correction of NLFs at week 2 after the initial treatment, the treating investigator will be directed to retreat the under corrected NLF(s).	Device: Hyaluronic acid Lunaphil Ultra (by Espad Pharmed Co.); Two treatments will be allowed over a 2-week period (initial treatment plus one touch-up) to achieve optimal correction of the NLFs based on investigator's opinion
Active Comparator: Juvederm Ultra 4® (by Allergan Co.); Juvederm Ultra 4® (by Allergan Co.) will be administered over a 2-week period (initial treatment plus one touch-up) to achieve optimal correction of the NLFs. In case of suboptimal correction of NLFs at week 2 after the initial treatment, the treating investigator will be directed to retreat the under corrected NLF(s).	Device: Hyaluronic acid Juvederm Ultra 4® (by Allergan Co.); Two treatments will be allowed over a 2-week period (initial treatment plus one touch-up) to achieve optimal correction of the NLFs based on investigator's opinion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Level of Improvement From Baseline in NLF Severity Score by Wrinkle Severity Rating Scale (WSRS)	The scores are from 1 to 5, 1 indicating no visible folds and 5 indicating extreme folds	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With an Improved Score From Baseline Based on Physician Global Aesthetic Improvement Scale (PGAIS)	The scores are from 1 to 5, 1 indicating exceptional improvement and 5 indicating worsened results	24 weeks
Number of NLFs Maintaining a Clinically Significant Improvement in NLF Severity Score by Wrinkle Severity Rating Scale (WSRS)	≥1-point reduction from baseline. The scores are from 1 to 5, 1 indicating no visible folds and 5 indicating extreme folds	24 weeks
The Injected Volume to Obtain Optimal Aesthetic Result	initial treatment + touch-up	2 weeks
The Number of NLFs Receiving Touch-up Treatment	Counting the number of NLF who need additional injection	2 weeks
Evaluation of Adverse Events During 24 Weeks	All reported AEs are classified based on the Medical Dictionary for Regulatory Activities (MedDRA) terms and are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	24 weeks

Collaborators and Investigators

• Sponsor: Espad Pharmed
• Investigators: Principal Investigator: Kamran Balighi, Prof. Derm, Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): November 11, 2023
• Study Completion (Actual): November 11, 2023

Study Registration Dates

• First Submitted: July 8, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: January 31, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Follicular; Immunologic Factors; Physiological Effects of Drugs; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: LUN.ESP.KB.IV.00

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
• product manufactured in and exported from the U.S.: No