THIODERM STRONG Compared to Juvéderm® VOLUMA® Lidocaine for the Treatment of Midface Volume Deficit

Study Overview
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Brief Summary
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This mono-center clinical investigation is intended to evaluate the safety and effectiveness of THIODERM STRONG (test device) in the correction of moderate to severe midface volume deficit compared to Juvéderm® VOLUMA® Lidocaine (comparator device).

Detailed Description
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The Investigation is an exploratory, prospective, randomized, subject and evaluator-blinded, split- face, single-centre study investigating the effectiveness and safety of THIODERM STRONG compared to Juvéderm® VOLUMA® Lidocaine for the treatment of moderate to severe midface volume deficit. 20 eligible Subjects will be included in this investigation, after the informed consent form (ICF) has been signed and relevant pre-treatment procedures, including medical history and pregnancy testing, have been performed. Subjects will receive injection in the midface region using THIODERM STRONG and Juvéderm® VOLUMA® Lidocaine until an optimal aesthetic result is achieved. The Blinded Evaluating Investigator will determine severity of the Subject's midface volume deficit using the 5-point MVDSS throughout the investigation (Baseline to Week 24). Baseline is defined as the assessment prior to administration of the IMDs. The same Investigator will assess the Subject using the 5-point MVDSS at all visits. An optional touch-up treatment can be performed at Week 4 upon discretion of the Unblinded Treating Investigator. The effectiveness and safety of the treatment will be evaluated after Day 1, 3 and 7 as well as at 4, 8, 16 and 24 weeks using objective and subjective outcome parameters. An interim analysis will be performed when all Subjects have completed the visit at Week 8.

Official Title
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An Exploratory, Prospective, Randomized, Subject and Evaluator-blinded, Split-face, Single-centre Trial Investigating the Effectiveness and Safety of THIODERM STRONG Compared to Juvéderm® VOLUMA® Lidocaine for the Treatment of Midface Volume Deficit (TIMI)

Conditions
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Mid Face Volume Deficit

Intervention / Treatment
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* Device: Thioderm Strong
* Device: Juvéderm VOLUMA Lidocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years at the time of screening (upper limit 75 years, inclusive). 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), shown by the same rating on both sides, assessed by the Blinded Evaluating Investigator. Healthy skin in the midface area and free of diseases that could interfere in cutaneous aging evaluation. Subject has a stable medical condition with no uncontrolled systemic disease. Females of childbearing potential must have a negative urine pregnancy test and must agree to use a highly effective method of birth control throughout the entire study1. 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). Willingness to abstain from any aesthetic or surgical procedures in the treatment area for the duration of study, including botulinum toxin injection (except glabella or forehead botulinum toxin treatment). 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: Females, who are pregnant and/or, lactating or planning to become pregnant during the clinical investigation. History of allergies or hypersensitivity to hyaluronic acid and/or to gram positive bacterial proteins, lidocaine, or any amide-based anaesthetic History of severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies. Tendency to keloid formation and/or hypertrophic scars. Presence of infectious, inflammatory, or proliferative cancerous or pre-cancerous lesions in the area to be treated. Recurrent (three times a year over the last year) herpes simplex in the treatment areas Known human immune deficiency virus-positive individuals. History or presence of any autoimmune or connective tissue disease Uncontrolled (or unstable) Diabetes mellitus or uncontrolled systemic diseases as per Investigator discretion. 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 Implantation of dermal fillers in the treatment area within the preceding 24 months prior to Visit 0 (Screening) and during the entire investigation 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 Facial lipolysis, including submental fat treatments, within the previous 12 months prior to Visit 0 (Screening) and during the entire investigation Bariatric surgery within 12 months prior to Visit 0 (Screening) and during the entire investigation. History of bleeding disorder and/or use of anticoagulant, antiplatelet or thrombolytic medication, including nutrition supplements that potentially prolong coagulation, from 10 days pre- to 3 days post-injection (initial treatment and touch-up treatment). Systemic glucocorticoids, including immunosuppressant or immunomodulators, within 8 weeks prior to undergoing investigational device injections. Patients suffering from untreated epilepsy. Patients with acute rheumatic fever with heart complications. Patients with symptoms of cardiac conduction disorders. Planned dental/oral surgery or modification (bridgework, implants) within four weeks prior to each injection and to a minimum of four weeks post injection (initial treatment, touch-up treatment). Beard longer than three-day beard, or excessive facial hair that could interfere in evaluation of treatment as judged by the Investigator. Subjects with active SARS-CoV-2019 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 0 (Screening). Any medical condition prohibiting the inclusion in the clinical investigation according to the judgment of the Investigator. Previous enrolment in this clinical investigation. Current participation in another clinical investigation, or treatment with any investigational drug/medical device within 30 days prior to clinical investigation Visit 0 (Screening), or 5 half-lives of the investigational drug, whichever is longer. Midface volume deficit due to a congenital defect, trauma, or abnormalities in facial adipose tissue distribution such as those associated with HIV related lipodystrophy. Subjects who experienced fat loss for a minimum of 10% of body weight 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. 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. 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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Split-Face Design with random assignment of test device and comparator device to be injected either into right or into left Mid Face Area
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group THIODERM LEFT<br>Split Face Design: Test Device left midface and Comparator Device right midface | Device: Thioderm Strong<br>* Test Device<br>Device: Juvéderm VOLUMA Lidocaine<br>* Comparator Device<br>|
| Other: Group JUVÈDERM LEFT<br>Split Face Design: Test Device right midface and Comparator Device left midface | Device: Thioderm Strong<br>* Test Device<br>Device: Juvéderm VOLUMA Lidocaine<br>* Comparator Device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Magnitude | To assess the effectiveness of THIODERM STRONG in reducing the severity of the midface volume deficit in comparison with Juvéderm® VOLUMA® Lidocaine based on Blinded Evaluating Investigator assessment at Week 24 as measured via the 5-point Midface Volume Deficit Severity Scale (MVDSS). | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Volume Injected | To assess required total volume for optimum aesthetic result for THIODERM STRONG compared to Juvéderm® VOLUMA® Lidocaine. | 24 Weeks | 
| Response Rate | To assess the proportion of responders after treatment with THIODERM STRONG in comparison with Juvéderm® VOLUMA® Lidocaine per treated side. | Day7; Week 4, 8, 16, and 24 | 
| Response Magnitude | To assess the change on the 5-point MVDSS from baseline after treatment with THIODERM STRONG in comparison with Juvéderm® VOLUMA® Lidocaine. | Day 7; Week 4, 8, and 16 | 
| Response Magnitude Photographic Review | Change of 5-point MVDSS from baseline to Day 7 and Week 4, 8, 16 and 24 based on the independent blinded evaluating panel's assessment per treated side. | Day7; Week 4, 8, 16, and 24 | 
| Aesthetic Improvement via GAIS - Investigator | Aesthetic improvement based on the Blinded Evaluating Investigator's assessment per treated side at Week 4, 8, 16 and 24 using the GAIS. | Day7; Week 4, 8, 16, and 24 | 
| Aesthetic Improvement via GAIS - Subject | Aesthetic improvement based on the Subject's assessment per treated side at Week 4, 8, 16 and 24 using the GAIS | Day7; Week 4, 8, 16, and 24 | 
| Volume Change via 3D Imaging | Volume change of the midface region at Day 7 and Week 4, 8, 16 and 24, based on 3D surface imaging in comparison to the baseline 3D surface image per treated side. | Day7; Week 4, 8, 16, and 24 | 
| Subject Satisfaction - Face-Q(TM) Outcome Scale | The extent of Subject´s satisfaction with treatment of the midface at Day 1, 3, 7 and Week 4, 8, 16 and 24 as assessed by the FACE-QTM Satisfaction with Outcome Scale per treated side. | Day 1, 3, and 7; Week 4, 8, 16, and 24 | 
| Subject Appearance Appraisal - Face-Q(TM) Satisfaction with Cheeks | The extent of Subject´s appearance appraisal at Day 1, 3, 7 and Week 4, 8, 16 and 24 as assessed by the FACE-QTM Satisfaction with Cheeks Scale per treated side and compared to the score at screening. | Day 1, 3, and 7; Week 4, 8, 16, and 24 | 
| Change of Nasolabial Fold Severity | Change of nasolabial fold severity measured by NLF-SRS from baseline to Day 7 and Week 4, 8, 16 and 24 based on the Blinded Evaluating Investigator's assessment per treated side. | Day7; Week 4, 8, 16, and 24 | 
| Pain Assessment | Subject´s pain assessment after each treatment on an 11-point scale, where 0 is no pain and 10 is the worst pain imaginable per treated side. | Day 0; Week 4 (in case of touch-up treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Midface, Volume Deficit, Hyaluronic Acid, Dermal Filler