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

• Sponsor: Organogenesis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00587834
• Collaborator: (none)
• Enrollment: 96
• Locations: 4
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 24
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gingival Recession	Device: Gintuit; Other: Autologous palatal tissue	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With at Least 2 mm Keratinized Tissue (KT) at 6 Months at the Gintuit Treated Site. [6 months]

   The superiority of Gintuit relative to a pre-defined standard (50% success) for a 2 mm KT threshold after six months.

Secondary Outcome Measures

1. Color Same as Adjacent Tissues After 6 Months (Superiority) [6 months]

   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.

2. Texture Same as Adjacent Tissues After 6 Months (Superiority) [6 months]

   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.

3. Percentage of Subjects With at Least 1 mm Keratinized Tissue (KT) at 6 Months at the Gintuit Treated Site. [6 months]

   The superiority of Gintuit relative to a pre-defined standard (80% success) for a 1 mm KT threshold after six months.

4. Patient Preference After 6 Months/Early Termination (Superiority) [6 months]

   Number of patients expressing preference for Gintuit.

5. Surgical Site Sensitivity Mild or Absent After 1 Week(Superiority) [6 months]

   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. Pain Absent After 3 Days (Superiority) [Day 3]

   Pain Assessment(Modified Intent-to-Treat Population)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nevins Perio, LLC	Boston	Massachusetts	United States	02114
2	Michigan Center for Oral Health Research	Ann Arbor	Michigan	United States	48106
3	Perio Health Professionals, PLLC	Houston	Texas	United States	77063
4	University of Texas Health Science Center - San Antonio	San Antonio	Texas	United States	78229-3900

Sponsors and Collaborators

• Organogenesis

Investigators

• Principal Investigator: Michael McGuire, DDS, Perio Health Professionals, PLLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organogenesis
• ClinicalTrials.gov Identifier: NCT00587834
• Other Study ID Numbers: 06-PER-002-CTX
• First Posted: Jan 7, 2008
• Last Update Posted: Nov 8, 2012
• Last Verified: Oct 1, 2012

• Additional relevant MeSH terms: Gingival Recession

Study Results

Participant Flow

Arm/Group Title	Gintuit and Autologous Free Gingival Graft (FGG)
Arm/Group Description	Single application of Gintuit and FGG (control); split-mouth design
Period Title: Overall Study
STARTED	96
COMPLETED	96
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Gintuit and Autologous Free Gingival Graft (FGG)
Arm/Group Description	Single application of Gintuit and FGG (control); split-mouth design
Overall Participants	96
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	87 90.6%
>=65 years	9 9.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.14 (13.13)
Sex: Female, Male (Count of Participants)
Female	52 54.2%
Male	44 45.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 7.3%
Not Hispanic or Latino	85 88.5%
Unknown or Not Reported	4 4.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	5 5.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 1%
White	87 90.6%
More than one race	0 0%
Unknown or Not Reported	3 3.1%
Region of Enrollment (participants) [Number]
United States	96 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Per protocol the first 2 subjects per Investigator were training subjects and evaluated for safety only. There were 11 training subjects and the remaining 85 subjects were analyzed for all efficacy outcomes.

Arm/Group Title	Gintuit
Arm/Group Description	Single application;split-mouth design
Measure Participants	85
Number (95% Confidence Interval) [percentage of participants]	95.3 99.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gintuit
	Comments	Superiority relative to a pre-defined standard (50% success)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact Bionomial Test
	Comments

2. Secondary Outcome

Title	Color Same as Adjacent Tissues After 6 Months (Superiority)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

See description in primary outcome measure.

Arm/Group Title	Gintuit Equally Red as Adjacent Tissue	Gintuit Not Equally Red as Adjacent Tissue
Arm/Group Description	Not Equally Red includes responses of "more red" and "less red"
Measure Participants	85	85
Control Equally Red as Adjacent Tissue	23 24%	0 NaN
Control Not Equally Red as Adjacent Tissue	56 58.3%	6 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gintuit, Gintuit Not Equally Red as Adjacent Tissue
	Comments	Compare participants with (1) Gintuit equally red and Control not equally red to (2) Gintuit not equally red and Control equally red
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	McNemar
	Comments

3. Secondary Outcome

Title	Texture Same as Adjacent Tissues After 6 Months (Superiority)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

See description in primary outcome measures.

Arm/Group Title	Gintuit Equally Firm as Adjacent Tissue	Gintuit Not Equally Firm as Adjacent Tissue
Arm/Group Description	Not Equally Firm includes responses of "less firm" and "more firm"
Measure Participants	85	85
Control Equally Firm as Adjacent Tissue	46 47.9%	0 NaN
Control Not Equally Firm as Adjacent Tissue	35 36.5%	4 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gintuit, Gintuit Not Equally Red as Adjacent Tissue
	Comments	Compare participants with (1)Gintuit equally firm and Control not equally firm to (2) Gintuit not equally firm and Control equally firm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	McNemar
	Comments

4. Secondary Outcome

Title	Percentage of Subjects With at Least 1 mm Keratinized Tissue (KT) at 6 Months at the Gintuit Treated Site.
Description	The superiority of Gintuit relative to a pre-defined standard (80% success) for a 1 mm KT threshold after six months.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

See description in primary outcome measure.

Arm/Group Title	Gintuit
Arm/Group Description	Single application;split-mouth design
Measure Participants	85
Number (95% Confidence Interval) [Percentage of Participants]	100 104.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gintuit
	Comments	Superiority relative to a pre-defined threshold (80%) success
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact binomial test
	Comments

5. Secondary Outcome

Title	Patient Preference After 6 Months/Early Termination (Superiority)
Description	Number of patients expressing preference for Gintuit.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

See description in primary outcome measure.

Arm/Group Title	Gintuit
Arm/Group Description	Single application of Gintuit and FGG (control); split-mouth design. Number of subjects preferring Gintuit over Control.
Measure Participants	85
Number (95% Confidence Interval) [participants]	61 63.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gintuit
	Comments	The proportion of Gintuit as the preferred procedure.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact binomial test
	Comments

6. Secondary Outcome

Title	Surgical Site Sensitivity Mild or Absent After 1 Week(Superiority)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

See description in primary outcome measures. The presence of Coe-Pak (protective periodontal dressing) at Week 1 prohibited the assessment of sensitivity for 14 subjects. The analysis was performed on 71 of the 85 subjects evaluated for efficacy.

Arm/Group Title	Gintuit Not Sensitive	Gintuit Sensitive
Arm/Group Description	Included ratings of None and Mild	Included ratings of Moderate and Severe
Measure Participants	71	71
Control Not Sensitive	67 69.8%	3 NaN
Control Sensitive	1 1%	0 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gintuit, Gintuit Not Equally Red as Adjacent Tissue
	Comments	Compare participants with (1) Gintuit not sensitive and Control sensitive to (2) Gintuit sensitive and Control not sensitive.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3173
	Comments
	Method	McNemar
	Comments	McNemar's paired comparison test

7. Secondary Outcome

Title	Pain Absent After 3 Days (Superiority)
Description	Pain Assessment(Modified Intent-to-Treat Population)
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	6 months
Arm/Group Title	Gintuit		Free Gingival Graft		Palatal Donation Site		Mouth		Other
Arm/Group Description	Adverse events occurring at the Gintuit treated site		Adverse events occurring at the autologous free gingival graft site		Adverse events occurring at the palatal donation site		Adverse events occurring in the mouth and not localized to the Gintuit, FGG, or palatal donation sites.		Adverse events occurring at any other location in the body or systemic conditions
All Cause Mortality
	Gintuit		Free Gingival Graft		Palatal Donation Site		Mouth		Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Gintuit		Free Gingival Graft		Palatal Donation Site		Mouth		Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/96 (0%)		0/96 (0%)		0/96 (0%)		0/96 (0%)		3/96 (3.1%)
General disorders
Chest Pains	0/96 (0%)	0	0/96 (0%)	0	0/96 (0%)	0	0/96 (0%)	0	1/96 (1%)	1
Infections and infestations
Pneumonia	0/96 (0%)	0	0/96 (0%)	0	0/96 (0%)	0	0/96 (0%)	0	1/96 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Metastatic Fibrous Histiocytoma	0/96 (0%)	0	0/96 (0%)	0	0/96 (0%)	0	0/96 (0%)	0	1/96 (1%)	1
Other (Not Including Serious) Adverse Events
	Gintuit		Free Gingival Graft		Palatal Donation Site		Mouth		Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/96 (0%)		0/96 (0%)		0/96 (0%)		0/96 (0%)		0/96 (0%)

Limitations/Caveats

Secondary outcome measures were tested with a closed testing strategy; therefore pain was not tested (no p-value) because previous endpoint (site sensitivity) failed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor can review communications prior to public release and can embargo communications regarding trial results for at least 30 days in advance of public release. The sponsor can request removal of any confidential or proprietary information provided by sponsor and extend such review period for another 90 days to file patent applications or take other steps to protect the sponsor's intellectual property interests.