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Trial registered on ANZCTR


Registration number
ACTRN12612000320853
Ethics application status
Approved
Date submitted
14/10/2011
Date registered
21/03/2012
Date last updated
29/01/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 2 bilateral (split-face) comparison study to assess two formulations of ELAPR (Tropoelastin) compared to Juvederm (Registered trademark) Ultra Plus for the treatment of moderate to severe nasolabial folds
Scientific title
A Phase 2 bilateral (split-face) comparison study to assess two formulations of ELAPR (Tropoelastin) compared to Juvederm (Registered trademark) Ultra Plus for the treatment of moderate to severe nasolabial folds in Healthy Volunteers
Secondary ID [1] 273440 0
NCT01463657
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
healthy human volunteers 278977 0
Skin aging 279244 0
Condition category
Condition code
Skin 279449 279449 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a phase 2 bilateral (split-face), (non-inferiority) comparison study to assess two formulations of ELAPR (Tropoelastin) compared to Juvederm (Registered Product) Ultra Plus for the treatment of moderate to severe Nasolabial folds (NLF). Patients presenting to the clinic for treatment of moderate to severe NLFs will be recruited to the study. Following a screening period of up to 28 days, patients who meet the entry requirements and none of the exclusion criteria will be randomized to receive treatment with one of two ELAPR (Tropoelastin) formulations. Patients will attend the nominated sites for all procedures and be treated by the study investigator. Patients will receive either ELAPR002b (Tropoelastin) or ELAPR002d (Tropoelastin) for the treatment of one NLF, and Juvederm (Registered Trademark) Ultra Plus for the treatment of the second, opposite Nasolabial fold. Treatments will be provided on Day 1 and repeated on Day 29 (if required) and day 57 (if required).
Each treatment will consist of up 15 injections in total, each consisting of up to 0.1 ml of product, according to the treating clinician, delivered to the mid to deep dermis of the skin of each Nasolabial fold using a 27G needle. The needle will be inserted at an approximate angle of 30 degrees parallel to the skin, and the product may be injected by a retrograde injection or by deposition of a bolus. ELAPR (Tropoelastin) and the control may be implanted parallel or perpendicular to the Nasolabial fold. Exactly the same technique will be used for the treatment of both Nasolabial folds for each patient. When the injection is completed the treated Nasolabial fold may be gently massaged if required to enable the implant material to conform to the contour of the surrounding tissues.
Following the treatment of the Nasolabial folds, each patient will then have the same preparations (ELAPR002b or ELAPR002d, and Juvederm (Registered Trademark) Ultra Plus implanted as a 0.1ml bolus into the mid-deep dermis of the skin of the medial aspect of the upper arm (left or right arm) using a 27G needle on Day 1. The arm chosen by the patient will receive two implants, approximately 20mm apart, proximal being the ELAPR (Tropoelastin) (according to randomisation) and distal being Juvederm (Registered Trademark) Ultra Plus. The centre of the implants (on the upper arms) will be marked with a needle point tattoo. The tattoo mark will assist in locating the implant sites.
Patients will have safety observations for 60 minutes after each treatment. Photographs of the patient's Nasolabial Folds and the upper arm implants will be taken before and after treatment and at each follow-up visit for record keeping purposes only.
The two 2mm skin biopsies will be collect at the same visit at either Day 57, Day 85 or Day 169 according to randomization from the upper arm implant sites. The 2mm skin biopsies will encompass the needle point tattoo at the centre of the implant site. The biopsy wounds will be allowed to heal by secondary intention wound healing, under a non-stick or waterproof dressing.
All Patients will return on Day 8, 29, (36), 57, (64) 85 and 169 for evaluation. If there is no further treatment at Day 29 to achieve optimum cosmetic result, then the Day 36 visit is omitted. If there is no further treatment at Day 57 to achieve optimum cosmetic result, then the Day 64 visit is omitted. Patients will have both upper arm biopsies scheduled for the same visit on either Day 57, Day 85 or Day 169.
At each visit, patients will be asked questions related to the status of the Nasolabial fold and upper arm implants, skin site texture, skin reactions and any activities undertaken which may impact on the implants. The physical presence of the Nasolabial fold implants will be assessed by the investigator at each visit. To assess the effects of ELAPR (Tropoelastin) and Juvederm (Registered Trademark) Ultra Plus subjective feedback on the comfort and feel of the implant sites will be collected for the Nasolabial folds using a Visual Analogue Scale based questionnaire.
Safety evaluations will consist of monitoring and recording of all spontaneously reported and observed adverse reactions to the study device, general physical examination and clinical laboratory safety testing.
Extension Protocol
An Extension protocol is being designed and will be submitted for approval prior to the first patient reaching the end of the current study. It will be designed to continue follow-up of those patients with persistent study device implant effects at the end of the current study period.
Intervention code [1] 269546 0
Treatment: Devices
Comparator / control treatment
Juvederm (Registered Trademark) Ultra Plus
Control group
Active

Outcomes
Primary outcome [1] 279793 0
To assess the effect of two formulations of ELAPR on change from baseline of the severity of the Nasolabial folds by the investigator and a blinded third party rater using the Wrinkle Severity Rating Scale (WSRS) (Day 2004) vs. active control
Timepoint [1] 279793 0
24 weeks
Primary outcome [2] 286782 0
To assess the effect of two formulations of ELAPR on change from baseline of the severity of the NLF against a Wrinkle Severity Rating Scale (WSRS) at 24 weeks vs. active control
Timepoint [2] 286782 0
24 weeks
Secondary outcome [1] 294442 0
To assess the acute and chronic safety of ELAPR (tropoelastin) collecting all adverse and serious adverse events, expected and unexpected reported throughout the study. These will be coded, analyzed and presented in the final study report
Timepoint [1] 294442 0
24 weeks
Secondary outcome [2] 294971 0
An assessment of the effect of two formulations of ELAPR (Tropoelastin) on the change from baseline of the severity of the Nasolabial folds using the Wrinkle Severity Rating Scale (WSRS).
Timepoint [2] 294971 0
24 weeks
Secondary outcome [3] 294972 0
An assessment of the persistence of the implant following histopathology and immunohistochemistry of the upper arm implant sites.
Timepoint [3] 294972 0
Collected at day 57, 85 or day 169 depending on allocation.

Eligibility
Key inclusion criteria
Moderate to severe Nasolabial folds scored using the Winkle Severity Rating Scale graded equally as a 3 or 4 out of 5 on both sides of the face
Good general health status
Able to give informed consent
Minimum age
25 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Clinically significant abnormalities of haematology or biochemistry testing
Bleeding diathesis, anticoagulant drugs, thrombocytopenia or clinically significant prolonged APTT or PT
Over the counter neutraceuticals and health supplements which may increase risks of bruising (e.g. chilli or capsicum)
Chronic use of aspirin, other non-steroidal anti-inflammatory drugs or other anti-platelet agents
Allergy to local anaesthetics
Systemic corticosteroids within last 12 weeks
Active infection at the treatment site
Treatment of either NLF other than with a hyaluronic acid (HA) dermal filler and treatment with a HA dermal filler within 18 months of enrolment
Any treatment with Botulinum toxin that in the investigator’s opinion may impinge on the appearance of the NLF treatment site
Mid and Lower face volumising treatments which in the view of the investigator may impinge on the appearance of the NLF region
Treatments to the implant site involving significant tissue ablation including lasers, dermabrasion and high strength chemical peels
Any serious medical condition which in the opinion of the investigator would have a strong possibility of requiring systemic corticosteroid medication
Pregnancy/lactation
History of keloid formation
Unstable Diabetes or metabolic disorders
A history of anaphylaxis or allergic reactions including any known hypersensitivity to Hyaluronic acid or lidocaine
Sensitivity to Juvederm (Registered Trademark) Ultra Plus or Juvederm (Registered Trademark) products.
Participation in any other clinical trial one month prior to treatment and for the duration of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Following a screening period of up to 28 days, subjects who meet the entry requirements will be enrolled to one of two Cohorts, Cohort A or B and randomly assigned to receive treatment ELAPR002d or ELAPR002b vs. control, Juvederm (registered trademark).
The patients will be notified at the end of the study which treatment they were allocated to.
The PI and study staff are not concealed to allocation.
All subjects will receive up to three treatments to their Nasolabial folds to obtain optimum cosmetic result, 21 days apart
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software (i.e. computerised sequence generation)
Once the patient has been recorded on the Subject Enrolment Log the SIN will be allocated (Randomisation table 9.1.3) which allocates treatment to the NLF.
Patients with an even SIN (02, 04, 06, 08, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 and 30) will have ELAPR to the right NLF and the control to the left, where patients with an odd SIN (01, 03, 05, 07, 09, 11, 13, 15, 17, 19, 21, 23, 25, 27 and 29) will have the ELAPR to the left NLF and the control to the right.
The first 15 patients SIN 01 – 15 are allocated to treatment ELAPR002d and the Juvéderm® Ultra Plus, then the remaining 15 patients SIN 16 – 30 are allocated to ELAPR002 b and the Juvéderm® Ultra Plus (a total of 30 patients).
The arm chosen (chosen by the patient and probably the non-dominant arm) will have two implants, approximately 20mm apart proximal being the ELAPR (ELAPR002b or ELAPR002d according to randomisation 9.1.3) and distal being Juvéderm® Ultra Plus. The randomisation table (9.1.3) assigns the day of the biopsies at the visit at Day 57, Day 85 or Day 169.
Patients with the SIN 01, 02, 03, 04, 05, 16, 17, 18, 19 and 20 will have their biopsies on Day 57. Patients with the SIN 06, 07, 08, 09, 10, 21, 22, 23, 24 and 25 will have both their biopsies at Day 85 and Patients with the SIN 11, 12, 13, 14, 15, 26, 27, 28, 29 and 30 will have their biopsies performed at Day 169 a total of 10 patients in each group.

Replacement post randomisation, pre treatment.
In the event a participant is randomised but withdraws from the study prior to treatment the participant will be replaced at the end of the randomisation cycle. The 2 digit subject identification number (SIN) determines the participant’s treatment allocation and biopsy date. The replacement is allocated the Replacement SIN. For example, if participant 14 is randomised and withdraws prior to treatment, then at the completion of the randomisation cycle (after all 29 participants have had their first treatment) participant 14 will be replaced with participant 44 who will be allocated treatment and date for biopsy according to the above schedule.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Nil
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
12/12/2011
Actual
18/01/2012
Date of last participant enrolment
Anticipated
Actual
12/05/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 4750 0
3000
Recruitment postcode(s) [2] 4751 0
7000

Funding & Sponsors
Funding source category [1] 270041 0
Commercial sector/Industry
Name [1] 270041 0
Elastagen Pty Ltd
Country [1] 270041 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Elastagen Pty Ltd
Address
Australian Technology Park
National Innovation Centre
4 Cornwallis Street
Eveleigh NSW 2015 Australia
Country
Australia
Secondary sponsor category [1] 269210 0
None
Name [1] 269210 0
Address [1] 269210 0
Country [1] 269210 0
Secondary sponsor category [2] 269211 0
None
Name [2] 269211 0
Address [2] 269211 0
Country [2] 269211 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271994 0
Bellberry Limited
Ethics committee address [1] 271994 0
229 Greenhill Road
Dulwich
South Australia 5065
Ethics committee country [1] 271994 0
Australia
Date submitted for ethics approval [1] 271994 0
27/06/2011
Approval date [1] 271994 0
11/11/2011
Ethics approval number [1] 271994 0
2011-08-393

Summary
Brief summary
This is a phase 2 bilateral (both sides of the face), comparison study to assess two formulations of ELAPR (Tropoelastin) compared to Juvederm (Registered Trademark) Ultra Plus for the treatment of moderate to severe Nasolabial folds. Patients presenting to the clinic for treatment of moderate to severe Nasolabial folds will be recruited to the study. Following a screening period of up to 28 days, patients who meet the entry requirements and none of the exclusion criteria will be randomized to receive treatment with one of two ELAPR (Tropoelastin) formulations.
Patients will attend the nominated sites for all procedures and be treated by the study investigator. Patients will receive either ELAPR002b (Tropoelastin) or ELAPR002d (Tropoelastin) for the treatment of one NLF, and Juvederm (Registered Trademark) Ultra Plus for the treatment of the second, opposite Nasolabial fold. Treatments will be provided on Day 1 and repeated on Day 29 (if required) and Day 57 (if required).
Each treatment will consist of up 15 injections in total, each consisting of up to 0.1 ml of product, at the discretion of the treating consultant delivered to the mid to deep dermis of the skin of each Nasolabial fold using a 27G needle. The needle will be inserted at an approximate angle of 30 degrees parallel to the skin, and the product may be injected by a retrograde injection or by deposition of a bolus. ELAPR (Tropoelastin) and the control may be implanted parallel or perpendicular to the Nasolabial fold. Exactly the same technique will be used for the treatment of both Nasolabial folds for each patient. When the injection is completed the treated Nasolabial fold may be gently massaged if required to enable the implant material to conform to the contour of the surrounding tissues.
Following the treatment of the Nasolabial folds, each patient will then have the same preparations (ELAPR002b or ELAPR002d, and Juvederm (Registered Trademark) Ultra Plus implanted as a 0.1ml bolus into the mid-deep dermis of the skin of the medial aspect of the upper arm (left or right arm) using a 27G needle on Day 1. The arm chosen by the patient will receive two implants, approximately 20mm apart, proximal being the ELAPR (Tropoelastin) (according to randomisation) and distal being Juvederm (Registered Trademark) Ultra Plus. The centre of the implants (on the upper arms) will be marked with a needle point tattoo. The tattoo mark will assist in locating the implant sites.
Patients will have safety observations for 60 minutes after each treatment. Photographs of the patient's Nasolabial Folds and the upper arm implants will be taken before and after treatment and at each follow-up visit for record keeping purposes only.
The two 2mm skin biopsies will be collect at the same visit at Day 57, Day 85 or Day 169 according to randomization from the upper arm implant sites. The 2mm skin biopsies will encompass the needle point tattoo at the centre of the implant site. The biopsy wounds will be allowed to heal by secondary intention wound healing, under a non-stick or waterproof dressing.
All Patients will return on Day 8, 29, (36), 57, (64) 85 and 169 for evaluation. If there is no further treatment at Day 29 to achieve OCR, then the Day 36 visit is omitted. If there is no further treatment at Day 57 to achieve OCR, then the Day 64 visit is omitted. Patients will have both upper arm biopsies scheduled for the same visit on Day 57, Day 85 or Day 169.
At each visit, patients will be asked questions related to the status of the Nasolabial fold and upper arm implants, skin site texture, skin reactions and any activities undertaken which may impact on the implants. The physical presence of the Nasolabial fold implants will be assessed by the investigator at each visit. To assess the effects of ELAPR (Tropoelastin) and Juvederm (Registered Trademark) Ultra Plus subjective feedback on the comfort and feel of the implant sites will be collected for the Nasolabial folds using a Visual Analogue Scale based questionnaire.
Safety evaluations will consist of monitoring and recording of all spontaneously reported and observed adverse reactions to the study device, general physical examination and clinical laboratory safety testing.
Extension Protocol
An Extension protocol is being designed and will be submitted for approval prior to the first patient reaching the end of the current study. It will be designed to continue follow-up of those patients with persistent study device implant effects at the end of the current study period.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 33271 0
Prof Greg Goodman
Address 33271 0
8-10 Howitt Street,
South Yarra, Victoria 3141
Country 33271 0
Australia
Phone 33271 0
03 9826 4966
Fax 33271 0
Email 33271 0
[email protected]
Contact person for public queries
Name 16518 0
Dr Robert Daniels
Address 16518 0
Elastagen Pty Ltd
Australian Technology Park
National Innovation Centre
4 Cornwallis Street
Eveleigh NSW 2015 Australia

P: +61 (2) 9209 4054
F:
P: +61 (2) 9209 4054
F: +61 (2) 9310 7232
M: +61 (0)405 822 275
www.elastagen.com


M: +61 (0)405 822 275
www.elastagen.com
Country 16518 0
Australia
Phone 16518 0
+61 (2) 9209 4054
Fax 16518 0
+61 (2) 9310 7232
Email 16518 0
[email protected]
Contact person for scientific queries
Name 7446 0
Dr Robert Daniels
Address 7446 0
Elastagen Pty Ltd
Australian Technology Park
National Innovation Centre
4 Cornwallis Street
Eveleigh NSW 2015 Australia
Country 7446 0
Australia
Phone 7446 0
+61 (2) 9209 4054
Fax 7446 0
+61 (2) 9310 7232
Email 7446 0
[email protected]

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No Supporting Document Provided



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