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Comparison of saypha Volume Lidocaine from 2 different manufacturing locations in correcting moderate to sever nasolabial folds
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Volume Lidocaine HQ | Experimental | Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility |
|
| Volume Lidocaine C1 | Active Comparator | Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Saypha Volume Lidocaine | Combination Product | 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 |
| 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;
Therefore, the lower the number, the better. | 24 Weeks |
| 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 |
| 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 |
Inclusion Criteria:
A subject must meet ALL of the following criteria to be eligible for the study:
Exclusion Criteria:
subject who meets ANY of the following criteria is NOT eligible for the study:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yuvell | Vienna | 1010 | Austria | |||
| Ordination Dr. Gaerner |
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Enrollment:110 (Subjects enrolled include subjects screened and randomized))
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| ID | Title | Description |
|---|---|---|
| FG000 | Saypha® VOLUME Lidocaine HQ | Subjects who had administration of saypha® VOLUME Lidocaine manufactured in HQ |
| FG001 | Saypha® VOLUME Lidocaine C1 | Subjects who had administation of Sapha® VOLUME manufactured in C1 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The data sets contain all data collected in the Intent-to-treat population (ITT), which is defined as all subjects who received the investigational device and have at least one post-treatment assessment N =109 The SAF (Safety analysis Set) also has N = 109 Number of subjects with trial completion at week 24: N =106
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| ID | Title | Description |
|---|---|---|
| BG000 | Volume Lidocaine HQ | Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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;
Therefore, the lower the number, the better. | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment, but for this analysis we have to consider the number of subjects with trial completion at Week 24, threfore an overal population of 106. | Posted | Count of Participants | Participants | 24 Weeks |
65 weeks. From day 0 ( IMP administration) until visit 9 ( week 65).
AEs will be detected at each visit by clinical examination and by asking the subject about the occurrence of AEs. Care should be taken not to introduce bias when eliciting AE information from the subject.In addition, the subjects will be instructed to immediately contact the investigator/study site in case of occurrence of any untoward event between visits.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Volume Lidocaine HQ | Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma HQ Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypothyroidism | Endocrine disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development - Head of Clinical Operations | Croma Pharma | +432262684680 | clinical.studies@croma.at |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 18, 2021 | Dec 16, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 26, 2021 | Dec 16, 2024 | SAP_001.pdf |
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prospective, randomized, double-blind, parallel-group, multi-center study
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Subjects will be randomized to receive products from one of 2 productions sites. (C1 and HQ, respectively); as the products appear in an identical fashion only the batch numbers will allow identification of the production site; as the allocation of batch numbers to the respective site is not disclosed to the study site team, the entire team will be masked until break of blind
|
| 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;
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 |
| 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;
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 |
| Vienna |
| 1180 |
| Austria |
| Privatklinik Waehring GmbH | Vienna | 1180 | Austria |
| Volume Lidocaine C1 |
Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Nasolabial fold severity scale - Grading by investigator | Count of Participants | Participants |
|
|
|
|
| Secondary | 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 | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. | Posted | Count of Participants | Participants | Week 4, week 36, week 52, week 65, week 78, week 104 |
|
|
|
| Secondary | 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;
Therefore, the lower the number, the better. | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. | Posted | Mean | Standard Deviation | score on a scale | Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 104 |
|
|
|
| Other Pre-specified | 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 | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups. | Posted | Count of Participants | Participants | Weeks 4, 24, 36, 52, 65, 78, and 104 |
|
|
|
| Other Pre-specified | 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. | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1 | Posted | Count of Participants | Participants | Weeks 4, 24, 36, 52, 65, 78, and 104 |
|
|
|
| Other Pre-specified | 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. | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1. | Posted | Count of Participants | Participants | Weeks 4, 24, 36, 52, 65, 78, and 104 |
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| Other Pre-specified | 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 | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1. | Posted | Count of Participants | Participants | Weeks 4, 36, 52, 65, 78, and 104 |
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| Other Pre-specified | 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). | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1. | Posted | Mean | Standard Deviation | score on a scale | Weeks 4, 24, 36, 52, 65, 78, and 104 |
|
|
|
| Other Pre-specified | 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. | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. In the protocol and statistical analysis plan, the analysis for this outcome measure was planned only for the overall population and not for the randomized subgroups Saypha® FILLER HQ and Saypha® FILLER C1. | Posted | Mean | Standard Deviation | units on a scale | Day 0 and Week 2. |
|
|
|
| Other Pre-specified | 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. | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment. | Posted | Count of Participants | Participants | Weeks 24, 36, 52, 65, 78, and 104 |
|
|
|
| Other Pre-specified | 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;
Therefore, the lower the number, the better. | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment | Posted | Count of Participants | Participants | Week 4, Week 24, Week 36, Week 52 and, optional at Week 65, Week 78 and Week 104 |
|
|
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| Other Pre-specified | 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 | The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment | Posted | Mean | Standard Deviation | score on a scale | Week 4, 24, 36, 52, 65, 78, and 104 |
|
|
|
| Other Pre-specified | 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.- | All safety analyses will be based on the safety analysis set, defined as all subjects who received the investigational device (109 subjects). TEAEs is defined as treatment-emergent adverse event, that can be local and non local. Local TEAEs are the AEs in treatment area or just around treatment area; Non-Local: are AEs accredited to an IMD dose, if the start of AE is at the time point of application or later. In the below data local and non-local are reported together under TEAEs. | Posted | Count of Participants | Participants | Day 0 until week 65 |
|
|
|
| 0 |
| 54 |
| 1 |
| 54 |
| 16 |
| 54 |
| EG001 | Volume Lidocaine C1 | Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in the Croma Pharma C1 Facility Saypha Volume Lidocaine: correction of Nasolabial Folds using injection of Saypha Volume Lidocaine manufactured in 2 different plants at Croma Pharma | 0 | 55 | 2 | 55 | 14 | 55 |
| EG002 | Overall Population (Saypha Volume Lidocaine HQ + C1) | Subjects randomized to be treated with Saypha Volume Lidocaine manufactured in both facilities | 0 | 109 | 3 | 109 | 30 | 109 |
| vertebral foraminal stenosis, | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| appendicitis | Infections and infestations | Non-systematic Assessment |
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| Administration site haematoma | General disorders | Non-systematic Assessment |
|
| Administration site pain | General disorders | Non-systematic Assessment |
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| Administration Site swelling | General disorders | Non-systematic Assessment |
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| Injection Site Pain | General disorders | Non-systematic Assessment |
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| Injection site pruritus | General disorders | Non-systematic Assessment |
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| Appendicitis | Infections and infestations | Non-systematic Assessment |
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| COVID 19 | Infections and infestations | Non-systematic Assessment |
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| Gastroenteritis | Infections and infestations | Non-systematic Assessment |
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| Gingivitis | Infections and infestations | Non-systematic Assessment |
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| Nasopharingitis | Infections and infestations | Non-systematic Assessment |
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| Tonsilitis | Infections and infestations | Non-systematic Assessment |
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| Hypercholesterolemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Muscle tightness | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Pathological fracture | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| vertebral foraminal stenosis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Pregnancy | Pregnancy, puerperium and perinatal conditions | Non-systematic Assessment |
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| Depression | Psychiatric disorders | Non-systematic Assessment |
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| Dysuria | Renal and urinary disorders | Non-systematic Assessment |
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| Hypertension | Vascular disorders | Non-systematic Assessment |
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| Venous Trombosis | Vascular disorders | Non-systematic Assessment |
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| Application site Swelling | General disorders | Non-systematic Assessment |
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Not provided
Not provided
| 2 = Moderate |
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| 3 = Severe |
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| 4 = Extreme |
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| Week 36 |
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| Week 52 |
|
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| Week 65 |
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| Week 78 |
|
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| Week 104 |
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| Week 24 |
|
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| Week 36 |
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| Week 52 |
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| Week 65 |
|
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| Week 78 |
|
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| Week 104 |
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| Week 36 |
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| Week 52 |
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| Week 65 |
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| Week 78 |
|
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| Week 104 |
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| Improvement |
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| Week 24 |
|
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| Week 36 |
|
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| Week 52 |
|
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| Week 65 |
|
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| Week 78 |
|
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| Week 104 |
|
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| Improvement |
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| Week 24 |
|
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| Week 36 |
|
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| Week 52 |
|
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| Week 65 |
|
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| Week 78 |
|
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| Week 104 |
|
|
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| Week 24 : Response Rate with improvement 1 grade |
|
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| Week 24 : Response Rate with improvement 2 grades |
|
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| Week 36 : Response Rate with improvement 1 grade |
|
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| Week 36 : Response Rate with improvement 2 grades |
|
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| Week 52 : Response Rate with improvement 1 grade |
|
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| Week 52 : Response Rate with improvement 2 grades |
|
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| Week 65 : Response Rate with improvement 1 grade |
|
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| Week 65 : Response Rate with improvement 2 grades |
|
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| Week 78 : Response Rate with improvement 1 grade |
|
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| Week 78 : Response Rate with improvement 2 grades |
|
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| Week 104 : Response Rate with improvement 1 grade |
|
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| Week 104 : Response Rate with improvement 2 grades |
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|
|
| Week 36 |
|
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| Week 52 |
|
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| Week 65 |
|
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| Week 78 |
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| Week 104 |
|
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| Injection at Week 2 - immediately after injection |
|
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| Injection at Week 2 - 15 minutes after injection |
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| Aesthetic effect still present - no |
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| Week 36 |
|
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| Week 52 |
|
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| Week 65 |
|
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| Week 78 |
|
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| Week 104 |
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| Week 24 after initial treatment |
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| Week 36 after initial treatment |
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| Week 52 after initial treatment |
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| Week 65 after initial treatment |
|
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| Week 78 after initial treatment |
|
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| Week 104 after initial treatment |
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| Week 24 |
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| Week 36 |
|
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| Week 52 |
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| Week 65 |
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| Week 78 |
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| Week 104 |
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| TEAES (local)- Causal Relationship with IMP (probable + definite) |
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| TEAES (non-local)- Causal Relationship with IMP (probable + definite) |
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| TEAES (local) - Causal Relationship with Procedure (probable + definite) |
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| TEAES (non-local) - Causal Relationship with Procedure (probable + definite) |
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| TEAES (local) - SAEs |
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| TEAES (non -local) - SAEs |
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