Study to Evaluate the Effectiveness, Safety and Long Term Safety of Saypha® FILLER Lidocaine for Lip Augmentation

Study Overview
=================
Brief Summary
-----------------
This is a prospective, open-label, multicentre, randomized study conducted to evaluate the effectiveness, safety and long-term safety of Saypha® FILLER Lidocaine for lip augmentation.

Detailed Description
-----------------
Following informed consent and screening, eligible subjects with moderate to severe deficiency of lip volume will be randomized to receive Saypha® FILLER Lidocaine from 1 of 2 manufacturing sites. The device will be injected into the submucosa of the lips, and subjects will return for follow-up assessments at Week 3, 6, 26, 52 and optional at Week 76 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 using the LFS, Lip Fullness Scale, at Week 6, 26, 52 after the treatment and optional at Week 76 and in comparison to Day 0. The upper and lower lip will be graded separately. 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.

Official Title
-----------------
A Prospective, Open-label, Multicentre, Randomized Study to Evaluate the Effectiveness, Safety and Long Term Safety of Saypha® FILLER Lidocaine for Lip Augmentation

Conditions
-----------------
Abnormal Lip

Intervention / Treatment
-----------------
* Combination Product: Saypha® FILLER Lidocaine (HQ)
* Combination Product: Saypha® FILLER Lidocaine (C1)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult female or male subjects 18 years of age at Screening/Baseline visit (Visit 1) Presence of approximately symmetrical very thin lips (minimal red lip shows) to moderately thick lips (moderate red lip shows) as assessed with the LFS (severity grade of 1 to 3 on both lips) as determined by the investigator at Visit 1 For females of childbearing potential only: negative urine pregnancy test at Visit 1, and must agree to use an highly effective method of contraception for the duration of the clinical investigation Healthy skin in the treatment area and free of diseases that could interfere in evaluation of treatment Willingness to abstain from any cosmetic or surgical procedures in the treatment area for the duration of the clinical investigation Willingness to take part in this clinical investigation documented by a personally signed/dated informed consent. Exclusion Criteria: Pregnancy, lactation, planned pregnancy or unwillingness to use contraception at any time during the study (for women of child-bearing potential only) History of mental disorders or emotional instability History of allergic reaction or hypersensitivity to hyaluronic acid, lidocaine or any amide-based anaesthetic Prior surgery, scars or tattoo to the upper or lower lip or lip line; surgery and tattooing are prohibited until end of clinical investigation Tooth gap, overbite, beard longer three-day beard, or excessive facial hair that could interfere in evaluation of treatment as judged by the investigator Presence of any abnormal lip structure, such as a scar or lump or severe lip asymmetry, as judged by the investigator Previous tissue augmenting therapy in the lip area (including lips, oral commissures, nasolabial folds, marionette and perioral lines) with HA or collagen filler, or laser treatment, chemical peeling, dermabrasion or mesotherapy within 12 months before Visit 1 and until end of clinical investigation Previous permanent implant or treatment with non-HA or non-collagen filler in the lip area (including lips, oral commissures, nasolabial folds, marionette and perioral lines) and until end of the investigation Previous toxin treatment in the lip area (including lips, oral commissures, nasolabial folds, marionette and perioral lines) within 9 months before Visit 1 and until end of clinical investigation Presence of cutaneous lesions, inflammatory and/or infectious processes (e.g. acne, herpes, etc.) or proliferative lesions in the treatment area Known human immune deficiency virus-positive individuals History of allergies against aesthetic filling products and recurrent (3 times a year) herpes simplex in the treated area Tendency to hypertrophic scars, keloid formation and/or pigmentation disorders History or presence of any autoimmune or connective tissue disease, or current treatment with immune therapy Uncontrolled systemic diseases (such as diabetes mellitus) Use of anticoagulant, antiplatelet or thrombolytic medication (e.g. acetylsalicylic acid) from 10 days pre- to three days post IMD injections Planned dental/oral surgery or modification (bridge-work, implants) within two weeks prior to initial IMD injection and to a minimum of four weeks post IMD injections Any medical condition which, in the investigator's opinion, prohibits the inclusion in the study Current or previous (within 30 days of enrolment) treatment with another investigational drug and/or medical device or participation in another clinical study Previous enrolment in this clinical investigation Any dependent relationship of the subject with the investigator, investigation site or Sponsor (e.g. employees or relatives) 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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saypha® FILLER HQ<br>Eligible subjects will undergo bilateral lip augmentation treatments with Saypha® FILLER Lidocaine manufactured in the Croma Pharma HQ Facility in order to correct moderate to severe deficiency of lip volume. The treatment will be administered at the Baseline visit (Day 0). | Combination Product: Saypha® FILLER Lidocaine (HQ)<br>* Saypha® FILLER Lidocaine is administered by injection into the lips. The volume applied depends on the size of the area which requires correction and will be selected by the investigator. A maximum volume of 2 mL for both lips in total (i.e., for upper plus lower lip) including touch up might be needed per treatment but the treatment should not exceed 10 mL in total per treatment or 20 mL per year.<br>|
| Active Comparator: Saypha® FILLER C1<br>Eligible subjects will undergo bilateral lip augmentation treatments with Saypha® FILLER Lidocaine manufactured in the Croma Pharma C1 Facility in order to correct moderate to severe deficiency of lip volume. The treatment will be administered at the Baseline visit (Day 0). | Combination Product: Saypha® FILLER Lidocaine (C1)<br>* Saypha® FILLER Lidocaine is administered by injection into the lips. The volume applied depends on the size of the area which requires correction and will be selected by the investigator. A maximum volume of 2 mL for both lips in total (i.e., for upper plus lower lip) including touch up might be needed per treatment but the treatment should not exceed 10 mL in total per treatment or 20 mL per year.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate in lip volume improvement | The proportion of subjects ('responders') with the lip volume improved by ≥1 point versus baseline value at 6 weeks after initial treatment based on the investigator live assessment using the validated Lip Fullness Scale (LFS). | 6 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of responders based on the investigator live assessment | The percentage of responders, based on the investigator live assessment at 6, 12 and optional 18 months after the initial treatment using the validated LFS. | 6, 12 and optional 18 months | 
| Percentage of responders based on the independent photographic reviewer´s assessments | The percentage of responders based on the independent photographic reviewer´s assessments before initial treatment and at Week 6, Month 6, 12 and optional Month 18 after initial treatment, based on photographs and using the validated LFS. | Week 6, Month 6, 12 and optional Month 18 | 
| Percentage of subjects with an improvement based on the investigator assessment using GAIS | The percentage of subjects with an improvement relative to baseline photographs, (subjects who have been rated as very much improved or much improved or improved), based on the investigator assessment at Week 6, Month 6, 12 and optional Month 18 after initial treatment using the 5-point GAIS. | Week 6, Month 6, 12 and optional Month 18 | 
| Percentage of subjects with an improvement based on subject assessment using GAIS | The percentage of subjects with an improvement relative to baseline photographs (subjects who have been rated as very much improved or much improved or improved), based on subject assessment at Week 6, Month 6, 12 and optional Month 18 after initial treatment, using the 5-point GAIS with results ranging from 1 to 5 with lower numbers indicating better improvement | Week 6, Month 6, 12 and optional Month 18 | 
| Subject Satisfaction using Face-Q questionnaire | The extent of subject´s satisfaction with overall outcome of the treatment, at Week 6, Month 6, 12 and optional Month 18 after initial treatment, assessed by the subject using the Face-Q TM Questionnaire Satisfaction with Outcome, a 6-item, Health-related Quality of Life Questionnaire with binary answer options (agree/disagree). | Week 6, Month 6, 12 and optional Month 18 | 
| Subject Satisfaction using Face-Q TM Questionnaire Satisfaction with Lips | The extent of subject's satisfaction with augmentation of lips, at Week 6, Month 6, 12 and optional Month 18 after initial treatment, assessed by the subject using the Face-Q TM Questionnaire Satisfaction with Lips, a 6-items Aesthetic Appearance Questionnaire with 5 pre-defined answer options between not at all bothered and extremely bothered | Week 6, Month 6, 12 and optional Month 18 | 
| Subject's perception of pain using the 11-point Numeric Pain Rating Scale | Subject's perception of pain after initial and touch-up treatment with Saypha® FILLER Lidocaine using the 11-point Numeric Pain Rating Scale (NPRS), where 0 is no pain and 10 is the worst pain imaginable. | Day1 | 
| Percentage of subjects demonstrating an aesthetic effect | Percentage of subjects demonstrating an aesthetic effect at Week 6, Month 6, 12 and optional Month 18 based on the investigator's life assessment. | Week 6, Month 6, 12 and optional Month 18 | 
| Injection volume required | Injection volume (initial and touch-up) required for an optimal augmentation of the lips with Saypha® FILLER Lidocaine. | Day1 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Moderate to Severe Lip Volume Deficit