Correction of Nasolabial Folds
Conditions
Brief summary
In this study, eligible subjects with moderate to severe nasolabial folds will be treated with Princess® FILLER Lidocaine and will return for follow-up assessments 2, 4, 24 and 36 weeks after the treatment. A Touch-up treatment may be done at Week 2, if deemed appropriate by the investigator
Detailed description
A prospective, open label, multicenter, post-market investigation. Following informed consent and screening, eligible subjects with moderate to severe nasolabial folds were treated with Princess® FILLER Lidocaine, and were to return for follow-up assessments 2, 4, 24 and 36 weeks after the initial treatment. A Touch-up treatment may be done at Week 2 after initial treatment, if deemed appropriate by the investigator. The performance of the investigational device evaluated by the investigator by assessing severity of nasolabial folds using the Nasolabial Folds Severity Rating Scale (NLF-SRS) (4, 24 and 36 weeks after the initial treatment and in comparison to Day 0) and global aesthetic improvement (4, 24 and 36 weeks after the initial treatment). The subject evaluated pain intensity associated with the treatment (at Day 0 and at Week 2 after initial treatment (if Touch-up treatment occurred)), and satisfaction with the treatment 4, 24 and 36 weeks after the initial treatment. The safety was evaluated based on occurrence of adverse events, which were collected throughout the investigation.
Interventions
Princess FILLER Lidocaine injection up to 10 ml given to the patients at baseline time point. After 2 week a touch up is given in case to be consider necessary.
Sponsors
Croma-Pharma GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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 2-3 according to the 5-grade 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
Subjects meeting any of the following criteria should not be enrolled: 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. Facial surgery or implantation of dermal fillers, absorbable and non-absorbable sutures, laser therapy, dermabrasion, or botulinum toxin application in the nasolabial region within previous twelve months, or chemical peeling within previous three months, 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 herpes simplex 10. Tendency to hypertrophic scars, keloid formation and/or pigmentation disorders 11. History or presence of any autoimmune or connective tissue disease, or current treatment with immune therapy 12. Diabetes mellitus or uncontrolled systemic diseases 13. Use of anticoagulant, antiplatelet or thrombolytic medication from ten days pre- to three days post injection 14. Any medical condition which, in the investigator's opinion, prohibits the inclusion in the study 15. Current or previous (within 30 days of enrolment) treatment with another investigational drug and/or medical device or participation in another clinical study 16. Previous enrolment in this clinical investigation 17. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Week 24 | Baseline and Week 24 | Change from baseline in average Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on investigator assessment at week 24 after the initial treatment. The left and right nasolabial folds were graded separately on the 5-point NLF-SRS then the average of the two sides was used for analysis. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme). |
| Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Week 24 | Week 24 | The proportion of subjects with at least 1 point reduction from baseline in Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on investigator assessment at week 24 after the initial treatment. The left and right nasolabial folds were graded separately. A subject is counted if the subject had at least one grade reduction over baseline on both nasolabial folds, on the 5-point NLF-SRS. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Aesthetic Improvement Based on Investigator Assessment at Weeks 4, 24 and 36 | Week 4, Week 24, Week 36 | The proportion of subjects with an aesthetic improvement over baseline (subjects who have been rated as very much improved or much improved or improved on both nasolabial folds), based on investigator assessment at weeks 4, 24 and 36 after the initial treatment and using the 5-point Global Aesthetic Improvement Scale (GAIS). GAIS grades are ranked as very much improved, much improved, improved, no change, and worse. |
| Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 4, Week 24, Week 36 | Summary of subjects' satisfaction with aesthetic outcome of the treatment at weeks 4, 24 and 36 after the initial treatment. Subjects were asked to rate their satisfaction with the treatment using one of the following categories: 'very unsatisfied', 'unsatisfied', 'neither unsatisfied nor satisfied', 'satisfied', or 'very satisfied'. |
| Change From Baseline in Average Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Weeks 4 and 36 | Baseline, Week 4, Week 36 | Change from baseline in average Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on investigator assessment at weeks 4 and 36 after the initial treatment. The left and right nasolabial folds were graded separately on the 5-point NLF-SRS then the average of the two sides was used for analysis. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme). |
| Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Independent Reviewer Assessment of Photographs at Week 24 | Week 24 | The proportion of subjects with at least 1 point reduction from baseline in Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on independent reviewer assessment of photographs at week 24 after the initial treatment. The left and right nasolabial folds were graded separately. A subject is counted if the subject had at least one grade reduction over baseline on both nasolabial folds, on the 5-point NLF-SRS. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme). |
| Average Pain Intensity Based on Subject Assessment Immediately After the Last Injection and 15 Minutes Thereafter for Initial and Touch-up Treatment | Baseline - Immediately after end of treatment, 15 minutes after end of treatment Week 2 - Immediately after end of treatment, 15 minutes after end of treatment | Average pain intensity based on subject assessment immediately after the last injection and about 15 minutes thereafter for initial treatment at baseline and for touch-up treatment at week 2 (if applicable). Subjects quantified the pain associated with the procedure using a semi-quantitative 11-point Numeric Pain Rating Scale (NPRS): 0 is no pain and 10 is the worst pain you can imagine. |
| Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Weeks 4 and 36 | Week 4, Week 36 | The proportion of subjects with at least 1 point reduction from baseline in Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on investigator assessment at weeks 4 and 36 after the initial treatment. The left and right nasolabial folds were graded separately. A subject is counted if the subject had at least one grade reduction over baseline on both nasolabial folds, on the 5-point NLF-SRS. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme). |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Princess® FILLER Lidocaine Princess FILLER Lidocaine injections up to 10 ml given to the patients at baseline time point
Princess FILLER Lidocaine: Princess FILLER Lidocaine injection up to 10 ml given to the patients at baseline time point. After 2 week a touch up is given in case to be consider necessary. | 60 |
| Princess® FILLER Lidocaine Princess FILLER Lidocaine injections up to 10 ml given to the patients at baseline time point
Princess FILLER Lidocaine: Princess FILLER Lidocaine injection up to 10 ml given to the patients at baseline time point. After 2 week a touch up is given in case to be consider necessary. | 120 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Princess® FILLER Lidocaine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants |
| Age, Continuous | 55.3 years STANDARD_DEVIATION 11.3 |
| Average Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade by Investigator | 2.72 score on a scale STANDARD_DEVIATION 0.44 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 60 Participants |
| Region of Enrollment Austria | 60 participants |
| Sex: Female, Male Female | 59 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 60 |
| other Total, other adverse events | 27 / 60 |
| serious Total, serious adverse events | 2 / 60 |
Outcome results
Primary
Change From Baseline in Average Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Week 24
Change from baseline in average Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on investigator assessment at week 24 after the initial treatment. The left and right nasolabial folds were graded separately on the 5-point NLF-SRS then the average of the two sides was used for analysis. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme).
Time frame: Baseline and Week 24
Population: The population used consists of all participants who received the investigational device and had at least one post-treatment assessment (e.g., first pain assessment after injection). Only subjects with available data for week 24 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Princess® FILLER Lidocaine | Change From Baseline in Average Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Week 24 | -1.8 score on a scale | Standard Error 0.6 |
Primary
Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Week 24
The proportion of subjects with at least 1 point reduction from baseline in Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on investigator assessment at week 24 after the initial treatment. The left and right nasolabial folds were graded separately. A subject is counted if the subject had at least one grade reduction over baseline on both nasolabial folds, on the 5-point NLF-SRS. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme).
Time frame: Week 24
Population: The population consists of all participants who received the investigational device and had at least one post-treatment assessment (e.g., first pain assessment after injection).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Princess® FILLER Lidocaine | Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Week 24 | 58 Participants |
Secondary
Average Pain Intensity Based on Subject Assessment Immediately After the Last Injection and 15 Minutes Thereafter for Initial and Touch-up Treatment
Average pain intensity based on subject assessment immediately after the last injection and about 15 minutes thereafter for initial treatment at baseline and for touch-up treatment at week 2 (if applicable). Subjects quantified the pain associated with the procedure using a semi-quantitative 11-point Numeric Pain Rating Scale (NPRS): 0 is no pain and 10 is the worst pain you can imagine.
Time frame: Baseline - Immediately after end of treatment, 15 minutes after end of treatment Week 2 - Immediately after end of treatment, 15 minutes after end of treatment
Population: The population used consists of all participants who received the investigational device and had at least one post-treatment assessment (e.g., first pain assessment after injection).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Princess® FILLER Lidocaine | Average Pain Intensity Based on Subject Assessment Immediately After the Last Injection and 15 Minutes Thereafter for Initial and Touch-up Treatment | Pain assessment immediately after end of treatment - Baseline | 1.5 score on a scale | Standard Deviation 1.4 |
| Princess® FILLER Lidocaine | Average Pain Intensity Based on Subject Assessment Immediately After the Last Injection and 15 Minutes Thereafter for Initial and Touch-up Treatment | Pain assessment 15 minutes after end of treatment - Baseline | 0.0 score on a scale | Standard Deviation 0 |
| Princess® FILLER Lidocaine | Average Pain Intensity Based on Subject Assessment Immediately After the Last Injection and 15 Minutes Thereafter for Initial and Touch-up Treatment | Pain assessment immediately after end of treatment - Week 2 | 2.1 score on a scale | Standard Deviation 1.8 |
| Princess® FILLER Lidocaine | Average Pain Intensity Based on Subject Assessment Immediately After the Last Injection and 15 Minutes Thereafter for Initial and Touch-up Treatment | Pain assessment 15 minutes after end of treatment - Week 2 | 0.0 score on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in Average Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Weeks 4 and 36
Change from baseline in average Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on investigator assessment at weeks 4 and 36 after the initial treatment. The left and right nasolabial folds were graded separately on the 5-point NLF-SRS then the average of the two sides was used for analysis. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme).
Time frame: Baseline, Week 4, Week 36
Population: The population used consists of all participants who received the investigational device and had at least one post-treatment assessment (e.g., first pain assessment after injection). Only subjects with available data for the respective visit were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Princess® FILLER Lidocaine | Change From Baseline in Average Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Weeks 4 and 36 | Week 4 | -1.98 score on a scale | Standard Error 0.4 |
| Princess® FILLER Lidocaine | Change From Baseline in Average Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Weeks 4 and 36 | Week 36 | -1.67 score on a scale | Standard Error 0.61 |
Secondary
Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Independent Reviewer Assessment of Photographs at Week 24
The proportion of subjects with at least 1 point reduction from baseline in Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on independent reviewer assessment of photographs at week 24 after the initial treatment. The left and right nasolabial folds were graded separately. A subject is counted if the subject had at least one grade reduction over baseline on both nasolabial folds, on the 5-point NLF-SRS. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme).
Time frame: Week 24
Population: The population used consists of all participants who received the investigational device and had at least one post-treatment assessment (e.g., first pain assessment after injection).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Princess® FILLER Lidocaine | Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Independent Reviewer Assessment of Photographs at Week 24 | 59 Participants |
Secondary
Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Weeks 4 and 36
The proportion of subjects with at least 1 point reduction from baseline in Nasolabial Folds-Severity Rating Scale (NLF-SRS) grade based on investigator assessment at weeks 4 and 36 after the initial treatment. The left and right nasolabial folds were graded separately. A subject is counted if the subject had at least one grade reduction over baseline on both nasolabial folds, on the 5-point NLF-SRS. NLF-SRS scores are ranked as 0 (None/minimal), 1 (Mild), 2 (Moderate), 3 (Severe) and 4 (Extreme).
Time frame: Week 4, Week 36
Population: The population used consists of all participants who received the investigational device and had at least one post-treatment assessment (e.g., first pain assessment after injection).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Princess® FILLER Lidocaine | Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Weeks 4 and 36 | Week 4 | 59 Participants |
| Princess® FILLER Lidocaine | Proportion of Subjects With ≥1 Point Reduction in Nasolabial Folds-Severity Rating Scale (NLF-SRS) Grade Based on Investigator Assessment at Weeks 4 and 36 | Week 36 | 58 Participants |
Secondary
Proportion of Subjects With Aesthetic Improvement Based on Investigator Assessment at Weeks 4, 24 and 36
The proportion of subjects with an aesthetic improvement over baseline (subjects who have been rated as very much improved or much improved or improved on both nasolabial folds), based on investigator assessment at weeks 4, 24 and 36 after the initial treatment and using the 5-point Global Aesthetic Improvement Scale (GAIS). GAIS grades are ranked as very much improved, much improved, improved, no change, and worse.
Time frame: Week 4, Week 24, Week 36
Population: The population used consists of all participants who received the investigational device and had at least one post-treatment assessment (e.g., first pain assessment after injection).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Princess® FILLER Lidocaine | Proportion of Subjects With Aesthetic Improvement Based on Investigator Assessment at Weeks 4, 24 and 36 | Week 4 | 59 Participants |
| Princess® FILLER Lidocaine | Proportion of Subjects With Aesthetic Improvement Based on Investigator Assessment at Weeks 4, 24 and 36 | Week 24 | 59 Participants |
| Princess® FILLER Lidocaine | Proportion of Subjects With Aesthetic Improvement Based on Investigator Assessment at Weeks 4, 24 and 36 | Week 36 | 58 Participants |
Secondary
Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36
Summary of subjects' satisfaction with aesthetic outcome of the treatment at weeks 4, 24 and 36 after the initial treatment. Subjects were asked to rate their satisfaction with the treatment using one of the following categories: 'very unsatisfied', 'unsatisfied', 'neither unsatisfied nor satisfied', 'satisfied', or 'very satisfied'.
Time frame: Week 4, Week 24, Week 36
Population: The population used consists of all participants who received the investigational device and had at least one post-treatment assessment (e.g., first pain assessment after injection).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 4 | Unsatisfied | 1 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 4 | Neither unsatisfied nor satisfied | 2 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 4 | Satisfied | 5 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 4 | Very satisfied | 51 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 4 | Missing | 1 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 24 | Unsatisfied | 2 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 24 | Neither unsatisfied nor satisfied | 1 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 24 | Satisfied | 9 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 24 | Very satisfied | 47 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 24 | Missing | 1 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 36 | Unsatisfied | 0 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 36 | Neither unsatisfied nor satisfied | 3 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 36 | Satisfied | 7 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 36 | Very satisfied | 49 Participants |
| Princess® FILLER Lidocaine | Satisfaction of Subjects With Aesthetic Outcome at Weeks 4, 24 and 36 | Week 36 | Missing | 1 Participants |