Saypha® Volume LIdocaine in Nasolabial Folds (SAVINO)

A Prospective, Randomized, Multicenter Study Evaluating Saypha® VOLUME Lidocaine* for the Correction of Nasolabial Fold

Comparison of saypha Volume Lidocaine from 2 different manufacturing locations in correcting moderate to sever nasolabial folds

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Nasolabial Folds
• Intervention / Treatment: Combination product: Saypha Volume Lidocaine

Detailed Description

Following informed consent and screening, eligible subjects with moderate to severe nasolabial folds will be randomized to receive saypha® VOLUME Lidocaine from 1 of 2 manufacturing sites. The device will be injected into the deep dermis or supraperiostal, and subjects will return for follow-up assessments at Week 2, 4, 24, 36, 52 and optional at Week 65, 78 and 104 after the treatment. A Touch-up treatment may be done at Week 2, if deemed appropriate by the investigator. The performance of the investigational device will be evaluated by the investigator by assessing severity of nasolabial folds using the Nasolabial Folds Severity Rating Scale (NLF-SRS) at Week 4, 24, 36, 52 after the treatment and optional at Week 65, 78 and 104 and in comparison to Day 0. Telephone visits will be performed approximately 24 hours post-administration to monitor possible adverse events. In case any adverse events are reported during the telephone visits an unscheduled visit should be performed.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1010
    • YUVELL
  • Vienna, Austria, 1180
    • Ordination Dr. Gaerner
  • Vienna, Austria, 1180
    • Privatklinik Waehring GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

A subject must meet ALL of the following criteria to be eligible for the study:

1. Male or female 18 years of age or older
2. Presence of two fully visible, approximately symmetrical nasolabial folds, with each of the folds scored with 2 or 3 according to the 5-grade Nasolabial Folds Severity Rating Scale (NLF-SRS) as assessed by the investigator
3. Healthy skin in the facial area and free of diseases that could interfere in cutaneous aging evaluation
4. Willingness to abstain from any aesthetic or surgical procedures in the treatment area for the duration of the clinical investigation
5. Written signed and dated informed consent

Exclusion Criteria:

subject who meets ANY of the following criteria is NOT eligible for the study:

1. Pregnancy, lactation, planned pregnancy or unwillingness to use contraception at any time during the study (for women of child-bearing potential only)
2. History of mental disorders or emotional instability
3. History of allergic reaction or hypersensitivity to hyaluronic acid, lidocaine, or any amide-based anaesthetic
4. Presence of silicone implant or another non-absorbable substance (permanent fillers) in the nasolabial region
5. Any superficial or deep facial surgery or injection or implantation of any dermal fillers (including but not limited to hyaluronic acid, collagen, calcium hydroxylapatite, poly-l-lactic acid, polymethylmethacrylate, autologous fat injections), application of any absorbable and non-absorbable sutures (thread) for any purpose including wound care and facial lifting, any laser therapy (including but not limited to Neodym-YAG, KTP, IPL, Diode lasers as well as Erbium-YAG, CO2 or other ablative lasers), dermoabrasion, or botulinum toxin application in the nasolabial region within previous 12 months prior to enrolment, or any chemical peeling procedures (including but not limited to glycolic acid, trichloroacetic acid or phenolic peels) within previous 3 months prior to enrolment, or planning to undergo such procedures in the treatment area during the study
6. Presence of infectious, inflammatory, or proliferative lesions in the nasolabial region
7. Cutaneous lesions in the treatment area
8. Known human immune deficiency virus-positive individuals
9. History of allergies against aesthetic filling products and recurrent (3 times a year) herpes simplex in the treated area
10. Tendency to hypertrophic scars and/or keloid formation
11. History or presence of any autoimmune or connective tissue disease, or current treatment with immune therapy
12. Uncontrolled systemic diseases (such as diabetes mellitus)
13. Bariatric surgery within 12 months prior to enrollment or planned during the clinical investigation
14. Use of anticoagulant or thrombolytic medication from 10 days pre- to 3 days post injection
15. Any medical condition which, in the investigator's opinion, prohibits the inclusion in the study
16. Current or previous (within 30 days of enrolment) treatment with another investigational drug and/or medical device or participation in another clinical study
17. Previous enrolment in this clinical investigation
18. Subjects whose participation in clinical trials is prohibited by the Austrian Medical Devices Act (e.g., persons with a legal custodian appointed due to mental disability, prisoners, soldiers and other members of the armed forces, civil servants)
19. Any dental procedures one month before until one month after treatment with the investigational device

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Volume Lidocaine HQ; Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility	Combination product: Saypha Volume Lidocaine; correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma. The amount injected depended on the size of the area to be corrected and the desired level of soft tissue augmentation. It was estimated that a maximum volume of 4 mL per treatment was needed but should not have exceeded 10 mL in total per treatment or 20 mL per year. and use in respective indications. The investigational device was administered to eligible subjects on investigation Day 0. A touchup treatment at Week 2 was optional at the investigator's discretion if full correction was
Active Comparator: Volume Lidocaine C1; Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility	Combination product: Saypha Volume Lidocaine; correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma. The amount injected depended on the size of the area to be corrected and the desired level of soft tissue augmentation. It was estimated that a maximum volume of 4 mL per treatment was needed but should not have exceeded 10 mL in total per treatment or 20 mL per year. and use in respective indications. The investigational device was administered to eligible subjects on investigation Day 0. A touchup treatment at Week 2 was optional at the investigator's discretion if full correction was

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder Rate in Reduction of Nasolabial Folds	The proportion of subjects with the NLF-SRS grade reduced by ≥1 point versus baseline at Week 24. This anaylsis is done per manufacturing site: C1 and HQ separately and for the overall population. A 'responder' is defined having at least ≥ 1 grade improvement as evaluated with the 5 point-validated NLF-SRS score on both sides of the face. Nasolabial Folds Severity Rating Scale (NLF-SRS) is a validated 5 grade scale where the lower number corresponds to: 0 = None/minimal: No visible/minimal nasolabial folds; = Mild: Shallow but visible nasolabial fold with a slight indentation;; = Moderate: Moderately deep nasolabial fold;; = Severe: Very deep nasolabial fold with prominent facial feature;; = Extreme: Extremely deep and long nasolabial fold with skin redundancy Therefore, the lower the number, the better.	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Responders at Other Time Points	The proportion of subjects with the NLF-SRS grade reduced by ≥1 point versus baseline at Week 4, Week 36, Week 52 and optional at Week 65, Week 78 and Week 104. A reduction in the score of the Nasolabial Folds Severity Rating Scale is considered an improvement as this reflects a decrease of the folds severity which is rated from 0 (none/minimal) to 4 (extreme). Individual NLF-SRS grades per visit calculated as the mean of grades assigned to the left and the right NLF, respectively On the Nasolabial Fold-Severity Rating Scale (NLF-SRS) higher scores indicate a greater severity of the folds: 0 = None/minimal: No visible/minimal nasolabial folds, 1 = Mild: Shallow but visible nasolabial fold with a slight indentation, 2 = Moderate: Moderately deep nasolabial fold, 3 = Severe: Very deep nasolabial fold with prominent facial feature, 4 = Extreme: Extremely deep and long nasolabial fold with skin redundancy	Week 4, week 36, week 52, week 65, week 78, week 104
Change Versus Baseline in Nasolabial Fold Severitry	The average change versus baseline in the NLF-SRS (Nasolabial Folds Severity Rating Scale) grade at Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 104 as evaluated by the investigator. A reduction in the score of the Nasolabial Folds Severity Rating Scale is considered an improvement as this reflects a decrease of the folds severity which is rated from 0 (none/minimal) to 4 (extreme). Nasolabial Folds Severity Rating Scale (NLF-SRS) is a validated 5 grade scale where the lower number corresponds to: 0 = None/minimal: No visible/minimal nasolabial folds; = Mild: Shallow but visible nasolabial fold with a slight indentation;; = Moderate: Moderately deep nasolabial fold;; = Severe: Very deep nasolabial fold with prominent facial feature;; = Extreme: Extremely deep and long nasolabial fold with skin redundancy Therefore, the lower the number, the better.	Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 104

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders With a ≥2-point Improvement	Percentage of responders with a ≥2-point improvement over Baseline on the 5-point NLF-SRS, based on investigator's live assessment at Weeks 4, 24, 36, 52, 65, 78, and 104 after initial treatment. On the Nasolabial Fold-Severity Rating Scale (NLF-SRS) higher scores indicate a greater severity of the folds: 0 = None/minimal: No visible/minimal nasolabial folds, 1 = Mild: Shallow but visible nasolabial fold with a slight indentation, 2 = Moderate: Moderately deep nasolabial fold, 3 = Severe: Very deep nasolabial fold with prominent facial feature, 4 = Extreme: Extremely deep and long nasolabial fold with skin redundancy	Weeks 4, 24, 36, 52, 65, 78, and 104
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Investigator's Assessment	Percentage of subjects with aesthetic improvement using the 5-point Global Aesthetzic Improvement Scavel (GAIS) (subjects who have been rated as "very much improved" or "much improved" or "improved"), based on investigator's assessment at Weeks 4, 24, 36, 52, 65, 78, and 104 after initial treatment, for each treatment location (right NLF, left NLF) separately and overall.	Weeks 4, 24, 36, 52, 65, 78, and 104
Percentage of Subjects With Aesthetic Improvement Using the 5-point GAIS Based on Subjects Assessment	Percentage of subjects with aesthetic improvement using the 5-point Global Aesthetzic Improvement Scavel (GAIS) (subjects who have been rated as "very much improved" or "much improved" or "improved"), based on subject's assessment at Weeks 4, 24, 36, 52, 65, 78, and 104 after initial treatment, for each treatment location (right NLF, left NLF) separately and overall.	Weeks 4, 24, 36, 52, 65, 78, and 104
Percentage of Responders With a ≥1-point Improvement Over Baseline on the 5-point NLF-SRS, Based on Evaluation by an Independent Reviewer of Photographs	Percentage of responders with a ≥1-point improvement over Baseline on the 5-point NLF-SRS, based on evaluation by an independent reviewer of photographs for Weeks 4, 36, 52, 65, 78, and 104 after initial treatment. On the Nasolabial Fold-Severity Rating Scale (NLF-SRS) higher scores indicate a greater severity of the folds: 0 = None/minimal: No visible/minimal nasolabial folds, 1 = Mild: Shallow but visible nasolabial fold with a slight indentation, 2 = Moderate: Moderately deep nasolabial fold, 3 = Severe: Very deep nasolabial fold with prominent facial feature, 4 = Extreme: Extremely deep and long nasolabial fold with skin redundancy	Weeks 4, 36, 52, 65, 78, and 104
Subject Satisfaction With Outcome of the Treatment, Assessed by the Face-Q Questionnaire "Satisfaction With Outcome"	Descriptive summary statistics for extent of subject satisfaction with outcome of the treatment, as assessed by the Face-Q questionnaire "Satisfaction with Outcome" at Weeks 4, 24, 36, 52, 65, 78, and 104 after initial treatment. Face-Q TM Questionnaire "Satisfaction with Outcome", a 6- tem, Health-related Quality of Life Questionnaire: The raw summed scale score is converted to a score from 0 to 100 by using the transformed sum score (Rasch model): Modified sum score ranges from 0 to 100 (low numbers correspond to low satisfaction).	Weeks 4, 24, 36, 52, 65, 78, and 104
Pain Intensity, as Evaluated by the Subject Using an 11-point NPRS	Descriptive summary statistics for pain intensity, as evaluated by the subject using an 11-point NPRS (where 0 is no pain and 10 is the worst pain imaginable) immediately after the last injection and 15 minutes thereafter, at Day 0 and optional at Week 2.	Day 0 and Week 2.
Percentage of Subjects Having an Aesthetic Effect	Percentage of subjects having an aesthetic effect, based on the investigator's life assessment at Weeks 24, 36, 52, 65, 78, and 104.	Weeks 24, 36, 52, 65, 78, and 104
The Proportion of Subjects With the NLF-SRS Grade Reduced by ≥1 Point Versus Baseline by Injection Technique and Device	The proportion of subjects with the NLF-SRS grade reduced by ≥1 point versus Baseline at Weeks 4, 24, 36, 52, 65, 78, and 104 by injection technique (retrograde, bolus) and device (needle, cannula). A reduction in the score of the Nasolabial Folds Severity Rating Scale is considered an improvement as this reflects a decrease of the folds severity which is rated from 0 (none/minimal) to 4 (extreme). Nasolabial Folds Severity Rating Scale (NLF-SRS) is a validated 5 grade scale where the lower number corresponds to: 0 = None/minimal: No visible/minimal nasolabial folds; = Mild: Shallow but visible nasolabial fold with a slight indentation;; = Moderate: Moderately deep nasolabial fold;; = Severe: Very deep nasolabial fold with prominent facial feature;; = Extreme: Extremely deep and long nasolabial fold with skin redundancy Therefore, the lower the number, the better.	Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 104
Average Change Versus Baseline in the NLF-SRS Grade at Week 4, 24, 36, 52, 65, 78, and 104 as Evaluated by the Investigator by Injection Technique ('Retrograde', 'Bolus') and Device ('Needle', 'Cannula')	The average change versus Baseline in the NLF-SRS grade at Weeks 4, 24, 36, 52, 65, 78, and 104 as evaluated by the investigator by injection technique ('retrograde', 'bolus') and device ('needle', 'cannula') On the Nasolabial Fold-Severity Rating Scale (NLF-SRS) higher scores indicate a greater severity of the folds: 0 = None/minimal: No visible/minimal nasolabial folds, 1 = Mild: Shallow but visible nasolabial fold with a slight indentation, 2 = Moderate: Moderately deep nasolabial fold, 3 = Severe: Very deep nasolabial fold with prominent facial feature, 4 = Extreme: Extremely deep and long nasolabial fold with skin redundancy	Week 4, 24, 36, 52, 65, 78, and 104
Safety Outcome	Occurrence and frequency of adverse events within each manufacturing site - HQ and C1 separately and for the overall population (HQ +C1). The safety of the investigational device will be monitored throughout the investigation, from visit 1 (Day 0 - baseline / treatment) until the final visit ( week 65 / visit 9). AEs were collected at each visit. In addition, the subjects were instructed to immediately contact the investigator by phone in case of occurrence of any untoward event between the visits.-	Day 0 until week 65

Collaborators and Investigators

• Sponsor: Croma-Pharma GmbH
• Investigators: Principal Investigator: Monika Sulovsky, Dr., Yuvell - H&P Ambulatorien GmbH (Study Site)

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Actual): May 27, 2021
• Study Completion (Actual): February 16, 2022

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: May 11, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 15, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Lidocaine
• Other Study ID Numbers: CPH-101-201477

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