Safety and Efficacy of Gintuit(TM)for Oral Soft Tissue Regeneration

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate Gintuit as a safe and effective alternative to palatal tissue in the treatment of subjects (with recession-type defects) who have an insufficient zone of attached gingiva associated with at least two nonadjacent teeth.

Official Title
-----------------
A Clinical Trial to Evaluate Gintuit (TM) (Allogeneic Cultured Keratinocytes and Fibroblasts in Bovine Collagen) as an Alternative to Tissue From the Palate to Enhance Oral Soft Tissue Regeneration and Wound Healing

Conditions
-----------------
Gingival Recession

Intervention / Treatment
-----------------
* Device: Gintuit
* Other: Autologous palatal tissue


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is at least 18 years of age but no more than 70 years of age. Subject has at least two non-adjacent teeth in contralateral quadrants of the same jaw with an insufficient zone (< or = 1mm) of attached gingiva that requires soft tissue grafting. (1-3 teeth may be treated. In case of adjacent teeth requiring grafting, only one tooth at each site will act as test or control tooth, but all teeth will get the same treatment). Root coverage is not desired at the time of grafting. Females of childbearing potential must have a documented negative urine pregnancy test. Subjects must have read, understood and signed an institutional review board (IRB) approved Informed Consent Form. Subjects must be able and willing to follow study procedures and instructions. Exclusion Criteria: Subject with class III recession in the presence of a shallow vestibule or class IV recession. Subject with vestibule depth of less than 7mm from base of recession. Subject with any systemic conditions that could compromise wound healing and preclude periodontal surgery (i.e., diabetes mellitus, cancer, human immunodeficiency virus (HIV), bone metabolic diseases). Subject who is currently receiving or has received within two months prior to study entry, systemic corticosteroids, immunosuppressive agents, radiation therapy, and/or chemotherapy which could compromise wound healing and preclude periodontal surgery. Subject with the presence of acute infectious lesions in the areas intended for surgery. Subject who has used any tobacco product within 3 months. Subject who is taking intramuscular or intravenous bisphosphonates. Subject with only molar teeth suitable for soft tissue grafting. Subject with teeth that have Miller Grade 2 or higher mobility. Subject with known hypersensitivity to bovine collagen and/or iodine (shellfish allergy). Subject who has received an investigational drug or biological/bioactive treatment within 30 days prior to study enrollment (medical or dental). Subject who was previously treated with Gintuit, Dermagraft or any other skin graft at the target site(s) or immediately adjacent teeth. Subject, who in the opinion of the investigator, for any reason other than those listed above, will not be able to complete the study per protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Within-subject design: one side of the mouth receives Gintuit | Device: Gintuit<br>* Application of Gintuit at Day 0 to the gingival bed<br>|
| Active Comparator: 2<br>Within-subject control: one side of mouth receives tissue harvested from the palate | Other: Autologous palatal tissue<br>* Tissue will be harvested from the subject's palate and placed on the gingival bed<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With at Least 2 mm Keratinized Tissue (KT) at 6 Months at the Gintuit Treated Site. | The superiority of Gintuit relative to a pre-defined standard (50% success) for a 2 mm KT threshold after six months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Color Same as Adjacent Tissues After 6 Months (Superiority) | An examiner assessed color of both treated sites compared with the adjacent, non-treated tissue. The assessment was recorded as More Red, Equally Red, or Less Red as compared to adjacent, non-treated tissue. A match in color with the surrounding tissue is considered a positive aesthetic outcome. | 6 months | 
| Texture Same as Adjacent Tissues After 6 Months (Superiority) | An examiner assessed texture of both treated sites compared with the adjacent, non-treated tissue. The assessment was recorded as More Firm, Equally Firm, or Less Firm as compared to adjacent, non-treated tissue. A match in texture with the surrounding tissue is considered a positive aesthetic outcome. | 6 months | 
| Percentage of Subjects With at Least 1 mm Keratinized Tissue (KT) at 6 Months at the Gintuit Treated Site. | The superiority of Gintuit relative to a pre-defined standard (80% success) for a 1 mm KT threshold after six months. | 6 months | 
| Patient Preference After 6 Months/Early Termination (Superiority) | Number of patients expressing preference for Gintuit. | 6 months | 
| Surgical Site Sensitivity Mild or Absent After 1 Week(Superiority) | The sensitivity of Gintuit, Free Gingival Graft (FGG) and palatal donation sites was assessed with a puff of air and rated by the Investigator as none, mild, moderate or severe sensitivity. The sensitivity of Control was determined as the most sensitive of FGG and palatal donation sites. | 6 months | 
| Pain Absent After 3 Days (Superiority) | Pain Assessment(Modified Intent-to-Treat Population) | Day 3 |