Trial Outcomes & Findings for Phase II Clinical Trial of Intraoral Grafting of Human Tissue Engineered Oral Mucosa (NCT NCT01834326)

Last Updated: 2021-09-05

Results Overview

The keratinized mucosa (KM) width will be measured by determining the distance from the crest of the edentulous ridge to the mucogingival line to the nearest millimeter with a Castroviejo caliper. The keratinized mucosa width of study subjects was measured prior to graft placement and then after two weeks, and after 4 weeks. The data provided shows the difference in keratinized mucosa width between the pre surgery measure and the post surgery measure. More mucosa width (positive numbers in mm) is an improvement, negative numbers (a decrease) would be less good.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

2 and 4 weeks post surgical graft

Results posted on

2021-09-05

Participant Flow

Participant milestones

Participant milestones
Measure	Palatal Oral Mucosa (POM) Graft Standard of care palatal oral mucosa (POM) graft will be taken from the palate and then surgically placed onto the defect area POM (Palatal oral mucosa): POM is a tissue graft harvested from the palate and surgically placed into the defect area	Ex Vivo Produced Oral Mucosa Equivalent Palatal biopsy will be harvested for fabrication of autogenous ex vivo produced oral mucosa equivalent (EVPOME) and then surgically placed onto the defect area EVPOME (autogenous ex vivo produced oral mucosa equivalent): EVPOME is manufactured from the subjects own oral cells and is implanted back in the subjects mouth after an approximately 30 day manufacturing process.
Overall Study STARTED	10	8
Overall Study COMPLETED	8	2
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase II Clinical Trial of Intraoral Grafting of Human Tissue Engineered Oral Mucosa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Palatal Oral Mucosa (POM) Graft n=10 Participants Standard of care palatal oral mucosa (POM) graft will be taken from the palate and then surgically placed onto the defect area POM (Palatal oral mucosa): POM is a tissue graft harvested from the palate and surgically placed into the defect area	Ex Vivo Produced Oral Mucosa Equivalent n=8 Participants Palatal biopsy will be harvested for fabrication of autogenous ex vivo produced oral mucosa equivalent (EVPOME) and then surgically placed onto the defect area EVPOME (autogenous ex vivo produced oral mucosa equivalent): EVPOME is manufactured from the subjects own oral cells and is implanted back in the subjects mouth after an approximately 30 day manufacturing process.	Total n=18 Participants Total of all reporting groups
Age, Customized Age 18 to 80 Years	10 Participants n=93 Participants	8 Participants n=4 Participants	18 Participants n=27 Participants
Sex/Gender, Customized Male	4 participants n=93 Participants	1 participants n=4 Participants	5 participants n=27 Participants
Sex/Gender, Customized Female	6 participants n=93 Participants	7 participants n=4 Participants	13 participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=93 Participants	8 Participants n=4 Participants	14 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants
Deficient band of keratinized mucosa	10 Participants n=93 Participants	8 Participants n=4 Participants	18 Participants n=27 Participants

PRIMARY outcome

Timeframe: 2 and 4 weeks post surgical graft

Population: Pregraft data for this outcome was not collected for the first subject, the protocol was written to collect the pregraft measurement after the first subject completed POM graft. For this reason there are only 7 data points in the POM arm of the study.

Outcome measures

Outcome measures
Measure	Palatal Oral Mucosa (POM) Graft n=7 Participants Standard of care palatal oral mucosa (POM) graft will be taken from the palate and then surgically placed onto the defect area POM (Palatal oral mucosa): POM is a tissue graft harvested from the palate and surgically placed into the defect area	Ex Vivo Produced Oral Mucosa Equivalent n=2 Participants Palatal biopsy will be harvested for fabrication of autogenous ex vivo produced oral mucosa equivalent (EVPOME) and then surgically placed onto the defect area EVPOME (autogenous ex vivo produced oral mucosa equivalent): EVPOME is manufactured from the subjects own oral cells and is implanted back in the subjects mouth after an approximately 30 day manufacturing process.
Clinical Increase in Zone (Width) of Keratinized Mucosa at Grafted Site 2 Week increase in keratinized mucosa	6.1 millimeters Standard Deviation 1.9	6.5 millimeters Standard Deviation 2.1
Clinical Increase in Zone (Width) of Keratinized Mucosa at Grafted Site 4 week increase in keratinized mucosa	5.1 millimeters Standard Deviation 1.4	4.5 millimeters Standard Deviation 2.1

SECONDARY outcome

Timeframe: 2, 4, 8 and 24 weeks after surgery

Graft measurements collected at each time point post graft surgery, 2 weeks, 4 weeks, 8 weeks and 24 weeks. Measurements collected, Horizontal Coronal (mm), Horizontal Apical (mm), Vertical between coronal and apical (mm), were used to determine the area of the graft as a trapezoid like shape. The area of the graft at each time point was compared to the area of the graft at the time of implantation (graft surgery) to determine the % of graft contracture from implantation thru each follow-up time point. Less graft contracture is considered a better outcome.

Outcome measures

Outcome measures
Measure	Palatal Oral Mucosa (POM) Graft n=8 Participants Standard of care palatal oral mucosa (POM) graft will be taken from the palate and then surgically placed onto the defect area POM (Palatal oral mucosa): POM is a tissue graft harvested from the palate and surgically placed into the defect area	Ex Vivo Produced Oral Mucosa Equivalent n=2 Participants Palatal biopsy will be harvested for fabrication of autogenous ex vivo produced oral mucosa equivalent (EVPOME) and then surgically placed onto the defect area EVPOME (autogenous ex vivo produced oral mucosa equivalent): EVPOME is manufactured from the subjects own oral cells and is implanted back in the subjects mouth after an approximately 30 day manufacturing process.
Graft Contracture 2 weeks post surgery	10 Percentage of graft contracture Standard Deviation 28	24 Percentage of graft contracture Standard Deviation 34
Graft Contracture 4 weeks post surgery	31 Percentage of graft contracture Standard Deviation 24	49 Percentage of graft contracture Standard Deviation 13
Graft Contracture 8 weeks post surgery	45 Percentage of graft contracture Standard Deviation 11	73 Percentage of graft contracture Standard Deviation 4
Graft Contracture 24 weeks post surgery	42 Percentage of graft contracture Standard Deviation 15	71 Percentage of graft contracture Standard Deviation 6

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 and 4 weeks after surgery

Graft blood flow measured using Laser Doppler flowmetry (LDF) of the graft at 2 and 4 weeks after surgery. LDF measurements (perfusion units) are taken at the site of the graft and compared to LDF readings at a contralateral site on the same subject. The comparison is reported as a percent. The percent is derived by dividing the LDF perfusion units at the graft site by the LDF perfusion units at the contralateral site in the same subject. It is not known how many perfusion units are necessary to adequately supply blood to a graft. By comparing the graft site to the contralateral site in the same patient at 2 and 4 weeks post surgery this data may provide more understanding of graft incorporation.

Outcome measures

Outcome measures
Measure	Palatal Oral Mucosa (POM) Graft n=8 Participants Standard of care palatal oral mucosa (POM) graft will be taken from the palate and then surgically placed onto the defect area POM (Palatal oral mucosa): POM is a tissue graft harvested from the palate and surgically placed into the defect area	Ex Vivo Produced Oral Mucosa Equivalent n=2 Participants Palatal biopsy will be harvested for fabrication of autogenous ex vivo produced oral mucosa equivalent (EVPOME) and then surgically placed onto the defect area EVPOME (autogenous ex vivo produced oral mucosa equivalent): EVPOME is manufactured from the subjects own oral cells and is implanted back in the subjects mouth after an approximately 30 day manufacturing process.
Graft Blood Flow 2 Week post surgery percent of perfusion units at graft site vs contralateral site on same subject	202 Percent perfusion units graft/contralat Standard Deviation 391	30 Percent perfusion units graft/contralat Standard Deviation 4
Graft Blood Flow 4 week post surgery percent of perfusion units at graft site vs contralateral site on same subject	206 Percent perfusion units graft/contralat Standard Deviation 234	222 Percent perfusion units graft/contralat Standard Deviation 210

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks after graft surgery

A biopsy of the graft is taken at 4 weeks after engraftment. The biopsy is stained for CD31 (cluster of differentiation 31) which is a marker for blood vessels. The number of blood vessels are counted in a standardized size of field. The number of blood vessels within the standardized field is reported. It is not known how much blood vessel development is necessary for graft success, but this study may provide insight into blood vessel development within EVPOME grafts over time.

Outcome measures

Outcome measures
Measure	Palatal Oral Mucosa (POM) Graft n=8 Participants Standard of care palatal oral mucosa (POM) graft will be taken from the palate and then surgically placed onto the defect area POM (Palatal oral mucosa): POM is a tissue graft harvested from the palate and surgically placed into the defect area	Ex Vivo Produced Oral Mucosa Equivalent n=2 Participants Palatal biopsy will be harvested for fabrication of autogenous ex vivo produced oral mucosa equivalent (EVPOME) and then surgically placed onto the defect area EVPOME (autogenous ex vivo produced oral mucosa equivalent): EVPOME is manufactured from the subjects own oral cells and is implanted back in the subjects mouth after an approximately 30 day manufacturing process.
Immunohistochemistry Using Anti-CD31 (Cluster of Differentiation 31) to Detect Blood Vessel Growth Into the Graft.	15 Number of blood vessels Standard Deviation 5	17 Number of blood vessels Standard Deviation 7

Adverse Events

Palatal Oral Mucosa (POM) Graft

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Ex Vivo Produced Oral Mucosa Equivalent

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Palatal Oral Mucosa (POM) Graft n=10 participants at risk Standard of care palatal oral mucosa (POM) graft will be taken from the palate and then surgically placed onto the defect area POM (Palatal oral mucosa): POM is a tissue graft harvested from the palate and surgically placed into the defect area	Ex Vivo Produced Oral Mucosa Equivalent n=8 participants at risk Palatal biopsy will be harvested for fabrication of autogenous ex vivo produced oral mucosa equivalent (EVPOME) and then surgically placed onto the defect area EVPOME (autogenous ex vivo produced oral mucosa equivalent): EVPOME is manufactured from the subjects own oral cells and is implanted back in the subjects mouth after an approximately 30 day manufacturing process.
Respiratory, thoracic and mediastinal disorders Viral cold	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
General disorders Temporary numbness in throat due to anesthetic	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	12.5% 1/8 • Number of events 1 • Life of study, 3 years.
Skin and subcutaneous tissue disorders Herpes Labialis	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
Musculoskeletal and connective tissue disorders Severed Tendon Right Bicep	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
Skin and subcutaneous tissue disorders Bruising, neck	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
Skin and subcutaneous tissue disorders Throbbing	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
General disorders Headache	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
Respiratory, thoracic and mediastinal disorders Sinus Infection	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
Skin and subcutaneous tissue disorders Keratin nodule	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
Gastrointestinal disorders Stomach flu	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
Skin and subcutaneous tissue disorders Intra oral herpes	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.
General disorders Lack of energy with feeling of fever	10.0% 1/10 • Number of events 1 • Life of study, 3 years.	0.00% 0/8 • Life of study, 3 years.

Additional Information

Stephen E. Feinberg

University of Michigan

Phone: 734 763 5963

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place