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

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.