Addition of Dehydrated Human Amnion-Chorion Membrane During Scaling and Root Planing

The study product BioXclude™ is an Amnion-Chorion allograft membrane, a new membrane made
from human amniotic tissue donated from elective Caesarean section births. Amniotic sacs have
been used since the early 1900's to promote skin wound healing. All donated tissue has been
carefully screened and tested to reduce the risk of transmitting disease. BioXclude™ is
commercially available as a dental wound covering, for bone reconstruction procedures, and as
a treatment for receding gums, and the manufacturer has met all federal requirements for
distributing this product. However, the use of the membrane for this research treatment of
periodontal disease is investigational. BioXclude™ does not meet the criteria for FDA
oversight as a drug, device or biologic and is regulated as a Human Cells, Tissues, and
Cellular and Tissue based product. The product is designed for use as wound covering in a
variety of dental applications.

Quadrants (right/left, upper/lower) of the mouth will randomly be assigned by block
randomization via flip of a coin with either 1) scaling and root planing alone, or 2) scaling
and root planing with 8 x 8mm Dehydrated Human Amnion/Chorion Membrane (dHACM) placement
within the periodontal pocket at >5mm sites. The participant will act as their own control.
There will be one side of the mouth that will receive the dHACM intervention with scaling and
root planning, and one side that will be the control (scaling and root planning only).
Depending on the extent of the disease (>5mm probing depths) the intervention may involve
upper and lower jaws on that side of the mouth or only one jaw per side (1-2
interventions/1-2 controls per mouth). The addition of dHACM will be a one-time placement.

The only research-related procedures that will differ from standard of care are standardizing
the x-rays (with custom bite block), placement of the dehydrated human amnion-chorion
membrane (dHACM), supra-gingival cleaning at 3 and 6 months (instead of supra- and
sub-gingival) and x-rays taken at 9 months.

The two examiners (board certified periodontists) completing the periodontal examination will
be blinded to the treatment allocated to the participant by the clinical provider (graduate
periodontal resident or hygienist). Clinical measurements which are standard of care of a
periodontal examination will include: probing depth, bleeding on probing, clinical attachment
level, mobility, and plaque index (Sillness and Loe index). Probing measurements will be made
at 6 location points on all teeth in the dentition using a calibrated University of North
Carolina (UNC) periodontal probe with readings made to the nearest millimeter. Clinical
attachment levels will be made from the cemento-enamel junction or nearest landmark. All
sites with probing depths measuring >4mm will be measured a second time, and the average of
the 2 readings will be used as the site-specific probing depth endpoint. Concomitant
medications and safety evaluation will be recorded at each visit. Any suspected adverse
events or allergic responses will be evaluated by the investigator.

Clinical measurements will be made at the following time points: baseline; Month 1; Month 3;
Month 6; Month 9. Four bitewing radiographs will be taken for evaluation with custom bite
mounting utilizing a long cone paralleling technique and will be made at: baseline; Month 9.
Baseline x-rays are the standard of care for a periodontal examination. Standardizing the
x-rays with a custom bite block and re-taking the x-rays at 9 months are for research-related
procedures. Participants will be instructed not to perform interproximal oral hygiene for 7
days following treatment. At the 1, 3, 6 and 9 month follow up visits, Participants will be
instructed on the Bass brushing technique as well as the proper use of dental floss as is
standard of care for oral hygiene instructions. At the 3 and 6-month visits, supra-gingival
plaque removal will be performed. At the completion of the study (9 months) supra- and
sub-gingival scaling will be performed as indicated for each participant. Plaque removal is
the standard of care for maintaining a periodontally diseased participant. For research due
to the placement of the membrane, sub-gingival cleaning will be avoided at 3 and 6 months and
the cleaning will be supra-gingival only. This differs from the standard of care, which would
have sub- and supra-gingival cleaning at 3 and 6 months. Cleaning will return to standard of
care at 9 months, where participants will have sub- and supra-gingival cleaning.

To summarize, the standard of care will be followed for the initial x-rays, clinical
measurements, scaling and root planing, 1 month re-evaluation, 3, 6 and 9 month cleaning
visits. For the standard of care non-standardized x-rays are normally used. For research
purposes, the investigators will be standardizing the x-rays with a custom bite block and
re-taking x-rays at 9 months. In addition for research purposes we will be placing the
dehydrated human amnion-chorion membrane (dHACM), and having supra-gingival cleanings at 3
and 6 months (instead of supra- and sub-gingival).

Three examiners (board certified periodontists) will be calibrated to each other for the
collection of the data and interexaminer reliability will be calculated. The three examiners
will be calibrated for probing depth and clinical attachment levels by reproducing clinical
measurements on a single participant until the measurements are consistently within 0.5 and
the percentage is 95 percent agreement

Inclusion Criteria:

- Stage III and IV periodontitis (generalized moderate to severe chronic periodontitis)

- At least 4 teeth (to include at least one qualifying tooth on the right and left side
of the mouth) with probing depths of 6 to 9 millimeters and bleeding on probing

- at least 18 years of age

- consent to be in the study

- non-emergent dental treatment

- American Society of Anesthesiologists (ASA) Class I or II (prticipants that are
systemically healthy or have a systemic condition that is well controlled and are able
to receive elective dental care)

Exclusion Criteria:

- <18 years old or >100 years old

- currently pregnant or within 6 months postpartum, nursing

- require antibiotic prophylaxis prior to dental procedures as outlined by the 2017
American Heart Association guidelines

- decisionally challenged adults

- ASA Class III or IV (patients that have non-controlled systemic conditions that are
unable to have elective dental care)

- had periodontal therapy within 6 months of baseline treatment visit

- antibiotic therapy within 3 months prior to enrollment

- chronic therapy within 1 month prior to enrollment with medications that could affect
periodontal status or healing