Saypha® VOLUME Lidocaine for Midface Augmentation

The clinical investigation is a randomized, subject- and evaluator-blinded, active treatment controlled, multicenter, clinical investigation, to demonstrate the non inferiority of saypha® VOLUME Lidocaine to one of the devices approved for the same indication (Juvéderm® Voluma™ XC).

This will be a multi-center, randomized, double-blind, comparator-controlled study. The study took place in the US at 16 sites.

The purpose of the current clinical investigation is to evaluate the effectiveness, safety and long-term safety of saypha® VOLUME Lidocaine for the correction of age-related moderate to severe volume deficit in the midface (augmentation of midface volume deficit), and to demonstrate its non-inferiority to one of the devices approved for the same indication (Juvéderm® Voluma™ XC). In addition, the duration of the aesthetic effect after implantation will be studied.

Approximately 486 subjects in total will be randomized and treated resulting in 437 evaluable subjects for the primary endpoint. Randomization will be in a 2:1 ratio (test device: 324, comparator device: 162).

Each subject will take part in the investigation for up to 92 weeks. The total anticipated duration of the investigation, from the first-subject-first visit to the last-subject-last-visit, is around 114 weeks, based on expected recruitment period of about 22 weeks.

Eligibility Criteria:
Inclusion Criteria: (baseline treatment)

1. Male or female subjects aged 22 - 75 years (inclusive) of age at Screening.
2. Subjects with bilateral, approximately symmetric moderate to severe midface volume deficit (severity scores of 2 or 3 on the 5-point Midface Volume Deficit Severity Scale), as assessed by the blinded investigator at the site.
3. Females of childbearing potential must have a negative urine pregnancy test and must agree to use an effective method of birth control throughout the entire study. Male subjects with female partners of child-bearing potential must agree to use contraception throughout the entire study (surgical sterilization or a physical barrier such as a condom).
4. Healthy skin in the midface area and free of diseases that could interfere in cutaneous aging evaluation.
5. Willingness to abstain from any aesthetic or surgical procedures in the treatment area for the duration of entire investigation, including botulinum toxin injection (except glabella or forehead botulinum toxin treatment).
6. Subjects who understand the purpose and conduct of the study and having given written informed consent and are willing and able to attend the study visits as judged by the investigator.

Exclusion Criteria: (baseline treatment)

1. Females, who are pregnant and/or, lactating or planning to become pregnant during the clinical investigation
2. History of severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies
3. History of hypersensitivity to hyaluronic acid preparations, lidocaine or any amide-based anesthetic
4. Tendency to keloid formation and/or hypertrophic scars and/ or have pigment disorders
5. Known human immune deficiency virus-positive individuals
6. Presence of infectious, inflammatory or proliferative cancerous or pre-cancerous lesions in the treatment area
7. Re-current (three times a year over the last year) herpes simplex in the treatment area
8. History or presence of any autoimmune or connective tissue disease, or current treatment with immuno-modulating therapy
9. Uncontrolled (or unstable) Diabetes mellitus or systemic diseases as per investigator discretion
10. Previous facial plastic surgery, tissue augmentation with silicone, fat or another non-absorbable substance (permanent fillers) and semi-permanent / long-lasting fillers (e.g., poly-L-lactic acid (PLLA), Polymethylmethacrylate (PMMA) filler) in the area of device application and during the entire investigation
11. Implantation of dermal fillers in the treatment area within the preceding 24 months prior to Visit 1 (Screening) and during the entire investigation
12. Subject has received any of the following aesthetic treatments in the midface area: e.g., laser therapy, absorbable and non-absorbable sutures (threads), dermabrasion, mesotherapy, micro-needling and/or botulinum toxin (including treatment of crow´s feet in the outer eye region) within the last 12 months prior to Visit 1, chemical peeling within the last three months prior to Visit 1 or is planning to undergo such procedures during entire investigation.
13. Facial lipolysis, including submental fat treatments, within the previous 12 months prior to Visit 1 (Screening) and during the entire investigation
14. Bariatric surgery within 12 months prior to Visit 1 (Screening) and during the entire investigation
15. History of bleeding disorder and/or use of anticoagulant, antiplatelet, thrombolytic medication, or anti-inflammatory drugs (oral/injectable corticosteroids or non steroidal anti-inflammatory drugs, e.g., Motrin® or Advil®) or other substances known to increase coagulation time (vitamins or herbal supplements, e.g., St. John's Wort, high doses of vitamin E supplements) from ten days pre- to seven days post injection (baseline treatment and touch-up treatment)
16. Planned dental/oral surgery or modification (bridge-work, implants) within four weeks prior to each injection and to a minimum of four weeks post injection baseline treatment and touch-up treatment
17. Beard longer than three-day beard, or excessive facial hair that could interfere in evaluation of treatment as judged by the investigator
18. Subjects who have one of the following assessments during the visual examinations at Visit 2 (Baseline): Snellen visual acuity test worse than 20/40 (with corrective eyewear, if applicable), abnormal confrontational visual field test, or abnormal ocular motility test.
19. Subjects with active COVID-19 infection and subjects with symptoms consistent with COVID-19 infection including any other respiratory symptoms/illnesses within the past 14 days unless tested negative prior to Visit 1 (Screening)
20. Any medical condition prohibiting the inclusion in the study according to the judgment of the treating investigator
21. Previous enrollment in this clinical investigation
22. Current participation in another clinical trial, or treatment with any investigational drug/medical device within 30 days prior to Visit 1 (Screening) or within five half-lives of an investigational drug, whichever is longer and during the entire investigation
23. Midface volume deficit due to a congenital defect, trauma, or abnormalities in facial adipose tissue distribution such as those associated with HIV related lipodystrophy
24. Subjects who experienced weight change for a minimum of 10% over the last 12 months (e.g., post bariatric patients), or subjects who have the intention to change eating habits that result in a weight gain or loss \>10% during the entire investigation
25. Any individual whose willingness to volunteer in this clinical investigation could be unduly influenced by the expectation, whether justified or not, of benefits associated with participation or of retaliatory response from senior members of a hierarchy in case of refusal to participate (e.g., persons with a legal custodian appointed due to mental disability, prisoners, soldiers and other members of the armed forces, civil servants).
26. Close affiliation with the investigator (e.g., a close relative, financially dependent on the study site) or subject who is an employee of the sponsor's company or group companies of the sponsor.

Inclusion criteria: (touch-up treatment)

1. Females of childbearing potential must have a negative urine pregnancy test

Exclusion criteria: (touch-up treatment)

1. Occurrence of a related Serious Adverse Event or Adverse Event of Special Interest (i.e., embolic events, with possible, probable, or causal relationship to an intravascular injection of the device, as changes in vision \[loss of vision, blurriness, double vision, pain in or around the eye, blindness, blind spots, problems moving the eyes\], skin changing color around the eyelids or around the site of injection, other embolic phenomenon, e.g., stroke, skin necrosis, or impending necrosis) during or after the previous injections
2. Subjects who experienced visual changes considered abnormal clinically significant or other serious medical conditions during or after the previous injections
3. Subjects who have one of the following assessments during the visual examinations: Snellen acuity test worse than 20/40 (with corrective eyewear, if applicable), abnormal confrontational visual field test, or abnormal ocular motility test.

Inclusion criteria: (repeat-treatment)

1. Subjects with bilateral, approximately symmetric moderate to severe midface volume deficit (severity scores of 2 or 3 on the 5-point MVDSS), as assessed by the blinded evaluator at the site. The subject does not have to return to his baseline severity to be permitted to receive a repeat-treatment.
2. Subject has completed initial treatment phase up to Visit 9 (SV1) and is willing to attend the study visits of the screening phase for repeat-treatment and repeat-treatment phase
3. Females of childbearing potential must have a negative urine pregnancy test
4. Healthy skin in the midface area and free of diseases that could interfere in cutaneous aging evaluation

Exclusion criteria: (repeat-treatment)

1. Occurrence of a related Serious Adverse Event or Adverse Event of Special Interest (i.e., embolic events with possible, probable, or causal relationship to an intravascular injection of the device, as changes in vision \[loss of vision, blurriness, double vision, pain in or around the eye, blindness, blind spots, problems moving the eyes\], skin changing color around the eyelids or around the site of injection, other embolic phenomenon, e.g., stroke, skin necrosis, or impending necrosis) during or after the baseline injection and/or touch-up injections
2. Occurrence of a related Adverse Event that occurred during the initial treatment phase, and is ongoing at the time of the repeat treatment (i.e., relationship is classified as "possible", "probable" or "causal relationship"; outcome is "not recovered / resolved", "recovering / resolving", "recovered / resolved with sequelae" or "unknown")
3. Subjects who experienced visual changes considered abnormal clinically significant or other serious medical conditions during or after the baseline or touch-up injections, respectively
4. Subjects who have one of the following assessments during the visual examinations: Snellen acuity test worse than 20/40 (with corrective eyewear, if applicable), abnormal confrontational visual field test, or abnormal ocular motility test
5. Subjects who became pregnant since start of the study or planning to become pregnant during the clinical investigation
6. Known human immune deficiency virus-positive individuals
7. Presence of infectious, inflammatory or proliferative cancerous or pre-cancerous lesions in the treatment area
8. Development of re-current (three times a year over the last year) herpes simplex in the treatment area since study start
9. Development of any autoimmune or connective tissue disease since study start, or current treatment with immuno-modulating therapy
10. Development of uncontrolled (or unstable) diabetes mellitus or systemic diseases since study start as per investigator discretion
11. Facial plastic surgery, tissue augmentation with silicone, fat or another non-absorbable substance (permanent fillers) and semi-permanent fillers (e.g., poly-L-lactic acid) in the area of device application and during the initial treatment phase of the investigation
12. Implantation of dermal fillers (other than the test and comparator device used in the investigation) in the treatment area during the initial treatment phase of the investigation
13. Subject has received any of the following aesthetic treatments in the midface area: e.g., laser therapy, absorbable and non-absorbable sutures (threads), dermabrasion, mesotherapy, micro-needling and/or botulinum toxin (including treatment of crow´s feet in the outer eye region), or chemical peeling during the initial treatment phase of the investigation or is planning to undergo such procedures during the repeat-treatment phase of the investigation
14. Facial lipolysis, including submental fat treatments during the initial treatment phase of the investigation
15. Bariatric surgery during the initial treatment phase of the investigation
16. Development of bleeding disorder and/or use of anticoagulant, antiplatelet, thrombolytic medication, or anti-inflammatory drugs (oral/injectable corticosteroids or non steroidal anti-inflammatory drugs, e.g., Motrin® or Advil®) or other substances known to increase coagulation time (vitamins or herbal supplements, e.g., St. John's Wort, high doses of vitamin E supplements) from ten days pre- to seven days post injection (repeat-treatment and touch-up treatment)
17. Planned dental/oral surgery or modification (bridge work, implants) within four weeks prior to the injection and to a minimum of four weeks post injection
18. Any medical condition prohibiting the inclusion for repeat-treatment according to the judgement of the treating investigator
19. Beard longer than three-day beard, or excessive facial hair that could interfere in evaluation of treatment as judged by the investigator
20. Previous enrollment in initial treatment phase of this clinical investigation and early termination, or significant incompliance with the protocol requirements
21. Current or previous treatment with another investigational drug and/or medical device or participation in another clinical study
22. Midface volume deficit due to a trauma, or abnormalities in facial adipose tissue distribution such as those associated with HIV related lipodystrophy
23. Subjects who experienced weight change for a minimum of 10% since study start or subjects who have the intention to change eating habits that result in a weight gain or loss \>10% during the entire investigation
24. Subjects with active COVID-19 infection and subjects with symptoms consistent with COVID-19 infection including any other respiratory symptoms/illnesses within the past 14 days unless tested negative prior to Visit RT1