Clinical Efficacy of Easy-graft CLASSIC for the Treatment of Peri-implantitis
Phase: NA
Conditions: Peri-Implantitis
Sponsor: Sunstar Americas

CONFIDENTIALITY STATEMENT 
This document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by federal or state law or regulations.  In any 
event, persons to whom the information is disclosed must be informed that the information is privileged 
or confidential and may not be further disclosed by them.  These restrictions on disclosure will apply 
equally to all future information supplied to you which is indicated as privileged or confidential. 
 
 
 
 
CREIGHTON UNIVERSITY SCHOOL OF DENTISTRY 
DEPARTMENT OF PERIODONTICS 
 
 
STUDY PROTOCOL 
Clinical Efficacy of easy graft Classic for the treatment of Peri-implantitis 
 
 
 
Protocol Number: 1015456 
 
Original Protocol Issue Date:  May 15, 2017 
 
 
Principal Investigator:     Lorenzo Mordini, DDS, MS 
 
 Creighton University School of Dentistry 
    Department of Periodontics 
                                            2500 California Plaza, Omaha, NE 68178 
 
Research Investigators:  Takanari Miyamoto, DDS, PhD, MSD 
 
 
 
    Creighton University School of Dentistry 
                                            Department of Periodontics 
 
Melissa S. Lang, DDS, MS 
 
 Creighton University School of Dentistry 
    Department of Periodontics 
 
 
 
Sponsor: SUNSTAR Americas, Inc. 
 

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Protocol Number:  CUSD2 
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Page 2 of 63  
Contents 
PROTOCOL SYNOPSIS ..........................................................................................................4 
1.0 
BACKGROUND .........................................................................................................5 
2.0 
SUMMARY AND STUDY RATIONALE .....................................................................11 
INVESTIGATIONAL DEVICE ....................................................................................15 
GUIDOR® easy-graft® CLASSIC ..............................................................................15 
GUIDOR® Bio-resorbable Matrix Barrier ...............................................................16 
3.0 
STUDY DESIGN .......................................................................................................16 
3.1 
Overall Study Design .................................................................................16 
Objectives ..............................................................................................................18 
3.3 
Subject Eligibility .......................................................................................20 
3.3.1 Inclusion Criteria ...........................................................................20 
3.3.2 Exclusion Criteria ..........................................................................21 
3.4 
Study Procedures ......................................................................................23 
3.4.1 Pre-Operative Treatment ................................................................23 
3.4.2 Study Treatments ...........................................................................24 
3.4.3 Other Therapy 25 
3.4.4 Postsurgical Care ...........................................................................25 
3.5 
Clinical Assessments ..................................................................................28 
3.5.1 Summary of Clinical Assessments.................................................28 
3.5.3 Probing Depths...............................................................................29 
3.5.4 O’Leary Plaque Index ....................................................................29 
3.5.5 Laboratory Assessments ................................................................30 
3.6 
Schedule of Investigational Events ...........................................................31 
3.6.1 Screening Visit (Visit 1) ................................................................31 
3.6.4 Post op – 1 Month (Visit 4)............................................................33 
3.6.6 6 Months Follow up. (Visit 6)........................................................35 
3.6.7  12 Months Follow up. (Visit 7).....................................................36 
3.7 
Summary of Clinical Assessments (revised by UoC to meet assessment for 
implant tooth) .......................................................................................................38 
3.7 
Radiography...............................................................................................44 
3.7.1 Exposure 
44 
3.7.2 Processing 
44 
3.7.3 Handling 
44 
3.7.4  Radiographic assessment .................................................................44 
3.7.5  Derivation or calculation of variable ...............................................45 
3.8 
Discontinuation of Treatment ..................................................................46 

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4.0 
ADVERSE EVENTS ..................................................................................................46 
Recording and Reporting Adverse Events ............................................................46 
Recording Adverse Events.....................................................................................47 
Grading Adverse Events ........................................................................................48 
Assigning Relationship of Adverse Events to Treatment .....................................48 
Serious Adverse Events .........................................................................................49 
Definition of a Serious Adverse Event ..................................................................49 
SAE report to Sponsor and IRB .............................................................................50 
5.0 
STATISTICAL AND ANALYTICAL PLAN ...................................................................51 
Intent to Treat Population ....................................................................................51 
Safety Population ..................................................................................................51 
Evaluable Population ............................................................................................51 
Missing Data ..........................................................................................................52 
Assessment of Safety ............................................................................................53 
6.0 
REGULATORY AND ADMINISTRATIVE REQUIREMENTS .......................................53 
6.1 
IRB Requirements ......................................................................................53 
6.2 
Protocol Amendments ..............................................................................54 
6.3 
Informed Consent ......................................................................................55 
APPENDIX I: 
QUESTIONNAIRES/SURVEYS ............................................................56 
 
 

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PROTOCOL SYNOPSIS 
Protocol Number 
1015456 
Title 
A STUDY TO DETERMINE EFFICACY OF EASY GRAFT CLASSIC FOR THE TREATMENT 
OF PERI-IMPLANTITIS 
Subject Population 
Subjects with history of Moderate to Severe Peri-implantitis 
Objectives 
TO ASSESS THE EFFECTVENESS OF EFFICACY OF EASY  GRAFT CLASSIC 
Number of Subjects 
Maximum of 15 subjects  
Number of Sites 
Maximum 20 implants 
Safety Endpoints 
Assessments of subject safety will be based upon tabulations of the incidence of  
adverse events. 
Efficacy Endpoints 
Stability and health of the attachment apparatus at 6 and 12 months by 
measuring:  
• Change from baseline in probing depth 
• Change from baseline in clinical attachment level 
• Change from baseline in width of the keratinized tissue  
• Change from baseline in radiographic A) bone regeneration ; B) pathology 
• Esthetic satisfaction from baseline to 12 months, as assessed by both the 
examiner  and the subject using the Visual Analog Scale (VAS), prior to and 
after viewing baseline photos 
• Subject pain/discomfort questionnaire 

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Study Design 
This study will be “case series”. Two periodontists will perform surgical 
procedures and record surgical measurements.  The blinded examiner will 
perform all other clinical assessments. 15 subjects will be enrolled.  Written 
informed consent will be obtained from each subject prior to any study related 
procedures. The study will follow subjects for safety and efficacy for 12 months 
after their surgical treatment.   
The day of surgery will be designated as Day 0. Subjects will have a guided bone 
regeneration surgery with GUIDOR® easy-graft® CLASSIC and GUIDOR® 
Bioabsorbable Membrane Matrix for the implants experiencing peri-implantitis. 
The surgical side will be assessed for osseous and implant surface anomalies. 
Intraoperative and postoperative measurements will be made and the flap will be 
closed with sutures.  
 
 
 
1.0 
BACKGROUND 
 
Peri-implantitis is an infectious condition of the tissues around dental implants causing loss of 
supporting bone and clinical signs of inflammation such as bleeding and/or suppuration on 
probing). The prevalence of this disease regards almost 10% of implants and almost 20% of 

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patients1,2. Many factors influence and increase prevalence (and the risk) of peri-implantitis. 
Some of those are previous history of periodontitis, smoking, diabetes as well as the type and 
frequency of follow-up care. It is worth noting that the prevalence of peri-implantitis varies 
depending on the parameters used in scientific papers. Bone loss and/or probing depth 
threshold may vary among different authors modifying the case definition.  
 
Different clinical protocols for treatment of peri-implantitis have been proposed, including 
mechanical debridement, the use of antiseptics and local or systemic antibiotics, as well as 
surgical access and regenerative procedures. Several attempts to combine the data of the 
available literature in a meta-analysis have failed in the past due to insufficient data.3,4,5,6, 7, 8 
 
Mombelli et all, in their review9 noted that almost all studies on the treatment of peri-
implantitis in humans do not satisfy the strict criteria for a randomized controlled trial (RCT). 
The main limitation was the absence of a true control group (no treatment or placebo). Trials at 
the highest level of evidence compared test procedures, both of which had an unclear 
 
1 Mombelli A, Müller N, Cionca N. The epidemiology of periimplantitis. Clin Oral Implants Res 2012;23(suppl 6):67–76. 
2 Lee CT, Huang YW, Zhu L, Weltman R. Prevalences of peri-implantitis and peri-implant mucositis: systematic review and meta-analysis. J Dent. 
2017 Jul;62:1-12. doi: 10.1016/j.jdent.2017.04.011. Epub 2017 May 3. Review. 
3 Klinge B, Gustafsson A, Berglundh T. A systematic review of the effect of anti-infective therapy in the treatment of peri-implantitis. J Clin  
Periodontol 2002;29(suppl 3):213–225; discussion 232–213. 
5 Renvert S, Roos-Jansaker AM, Claffey N. Non-surgical treatment of peri-implant mucositis and peri-implantitis: A literature review. J Clin 
Periodontol 2008;35:305–315.  
6 Renvert S, Polyzois I, Claffey N. Surgical therapy for the control of peri-implantitis. Clin Oral Implants Res 2012;23(suppl 6):84–94. 
7 Muthukuru M, Zainvi A, Esplugues EO, Flemmig TF. Non-surgical therapy for the management of peri-implantitis: A systematic review. Clin Oral 
Implants Res 2012;23(suppl 6):77–83. 
8 Esposito M, Grusovin MG, Worthington HV. Treatment of periimplantitis: What interventions are effective? A Cochrane systematic review. Eur 
J Oral Implantol 2012;5(suppl):s21–s41.  
9Mombelli A, Moene R, Decaillet F. Surgical treatments of periimplantitis. Eur J Oral Implantol 2012;5(suppl):s61–s70 

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Page 7 of 63  
outcome. As it is difficult to recruit sufficient numbers of patients with peri-implantitis to take 
part in a true randomized trial, some studies may have been underpowered.  
 
In terms of outcomes, there is inconsistency about primary treatment goals and minimally 
required observation periods. A recent Cochrane systematic review 10  included nine 
randomized controlled trials in an attempt to identify the most effective interventions for 
treating peri-implantitis around osseointegrated oral implants. The authors concluded that 
there is no reliable evidence suggesting which could be the most effective interventions for 
treating peri-implantitis. A review by Heitz-Mayfield and Mombelli11 covered reports that 
evaluated the effect of treatment, regardless if they were randomized trials or not.  The 
available evidence does not provide specific recommendations or standard protocol for peri-
implantitis treatment. Successful treatment outcomes at 12 months were reported in a 
majority of patients in 7 studies. Despite favorable short-term outcomes were reported in many 
studies, failure of treatment, progression or recurrence of disease and implant loss were 
reported too. The main limitation of systematic reviews is the heterogeneity in study design, 
length of follow-up, and exclusion/inclusion criteria. 
 
 
10Esposito M, Grusovin MG, Worthington HV. Interventions for replacing missing teeth: Treatment of peri-implantitis. Cochrane Database Syst 
Rev 2012;1 
11Heitz-Mayfield and Mombelli. The therapy of peri-implantitis: a systematic review. Int J Oral Maxillofac Implants. 2014;29 Suppl:325-45. doi: 
0.11607/jomi.2014 suppl 

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Daugela et al12 reported that in case of evident bone loss and pocket formation deeper than 5 
mm, the surgical treatment seemed to be the only effective one in managing peri-implantitis 
defect. Surgical regenerative treatment resulted in predictable improvement of peri-implant 
clinical and radiographic parameters although this statement is limited on available studies 
without proper control arm, as at the time there is a lack of controlled studies comparing 
effectiveness of surgical regenerative and non-regenerative procedures to support scientific 
evidence if regenerative procedures provide better outcomes. 
 
Currently there is a lack of clear recommendation regarding choice of biomaterials for peri-
implant bone regeneration due to high heterogeneity among the studies. From the clinical 
point of view, surgical regenerative treatment is a relevant treatment option of intrabony 
defect component in addition to pre- and postsurgical hygiene maintenance phases and 
successful implant surface decontamination. Regenerative procedures, with the application of 
bone graft materials in combination or not with barrier membranes seem to give consistent 
results in the term of hard and soft tissues healing of the peri-implantitis defect.   
Regenerative treatment of peri-implantitis lesions can be performed in cases with considerable 
pocket formation and bone loss after the acute infection has been resolved and proper oral 
hygiene has been instituted.  Reported clinical studies indicate that considerable bone 
regeneration and re-osseointegration can be obtained by using various types of bone graft 
materials and membranes. Meta-analysis of latest systematic literature review xi revealed that 
 
12Daugela P, et alSurgical Regenerative Treatments for Peri-Implantitis: Meta-analysis of Recent Findings in a Systematic Literature Review. J 

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the weighted mean of marginal bone level change was 1.97 mm, PD reduction was 2.78 mm 
and BOP reduced by 52.5% by treatment with regenerative treatment. However, a different 
compatibility between bone grafting material and chemically and mechanically decontaminated 
implant surface might bring a different clinical outcome.   
 
As far as the use of alloplastic grafting material, only two papers were identified in the 
literature. Roos-Jansåker et al. 13, 14 evaluated regenerative treatment of peri-implantitis 
comparing a bone substitute with or without a barrier membrane. Peri-implant defects were 
treated with a phytogenic calcium carbonate bone substitute (Algipore) or with the bone 
substitute and a resorbable synthetic membrane (Osseoquest). Successful treatment outcome 
(no PD ≤ 5 and no further bone loss 12mo after treatment) was on 93% of patient treatment 
with bone substitute and membrane and 89% of patients treated with bone substitute only.  
Schwarz 
et 
al
15
 filled 
peri-implant 
defects 
with 
either 
a 
synthetic nano-
crystalline hydroxyapatite (Ostim) or a bovine-derived xenogenic bone mineral (BioOss), and 
covered with a collagen membrane (Bio-Gide). Within the limits of the present case series they 
concluded that at 12 months after surgery both therapies resulted in clinically important PD 
reductions and CAL gains. 
 
Oral Maxillofac Res 2016; 9 (3): e15 
13Roos-Jansåker A-M, Renvert H, Lindahl C, Renvert S. Surgical treatment of peri-implantitis using a bone substitute with or without a 
resorbable membrane: A prospective cohort study. J Clin Periodontol 2007;34:625–632. 
14Roos-Jansåker A-M, Lindahl C, Persson GR, Renvert S. Long-term stability of surgical bone regenerative procedures of peri-implantitis lesions 
in a prospective case-control study over 3 years. J Clin Periodontol 2011;38:590–597. 
15 Healing of intrabony peri-implantitis defects following application of a nanocrystalline hydroxyapatite (Ostim) or a bovine-derived xenograft 
(Bio-Oss) in combination with a collagen membrane (Bio-Gide). A case series. Schwarz F, Bieling K, Latz T, Nuesry E, Becker J J Clin 
Periodontol. 2006 Jul;33(7):491-9. 

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Due to scarcity of literature on the use of alloplast on peri-implant treatment, the purpose of 
the study is to assess the effectiveness of the novel in-situ hardening β -TCP material, Easy-
Graft® CLASSIC and polylactide based biodegradable membrane, GUIDOR® Biodegradable 
Matrix Barrier, following clinically adequate decontamination procedures. The author thinks  
that the specific properties of this grafting material may favor treatment of peri-implantitis. A 
recent study by Canullo16 et al. analyzed the efficacy of Easy-Graft® CLASSIC on the treatment of 
peri-implantitis. After removal of granulomatous tissue and decontamination of the titanium 
exposed implant surface, Easy-Graft was placed on the defect as a protection from soft tissue 
invasion.   The authors noted a pronounced increase in mucosal recession and clinical 
attachment level with stable peri-implant conditions at six and 12 months. Plaque index, 
bleeding on probing and probing depths values were significantly reduced at six and 12 months. 
Radiographic analysis demonstrated from partial to complete filling of the defect in all of the 
cases at six and 12 months.  
Easy-graft remains moldable until it comes in contact with blood or tissue fluids. When the 
material is soaked in blood in bone defects it hardens in a few minutes to form stable porous 
scaffold for bone regeneration. This characteristic of graft material gives better handling for the 
clinician. The hardening of the material could provide an increased stability of the blood clot 
around implant defect and favor hard tissue deposition and maturation.  The Easy-Graft® 
CLASSIC manufacturer recommends GUIDOR® Bioabsorbable Membrane Matrix to be used 
 
16 Canullo L, Peñarrocha Oltra D, Tallarico M, Aloy Prosper A, Chocer H, Peñarrocha Diago M. Surgical treatment of circumferential and 
semicircumferential defects due to periimplantitis: a prospective case series cohort study. J Oral Science Rehabilitation. 
2016 Dec;2(4). 

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Page 11 of 63  
simultaneously in order to maximize its effects. The main difference between this proposed 
study and Canullo’s will be the use of GUIDOR® Bioabsorbable Membrane Matrix in conjunction 
with Easy-Graft® CLASSIC 
 
The authors of this present study considered the outcome of the peri-implant surgical therapy 
successful if: implant survival with no peri-implant probing depths (PD) ≥ 5 mm, with 
concomitant bleeding on probing (BOP) and no suppuration, in addition to no additional or 
progressive bone loss. If these criteria were met, it can be assumed that no further intervention 
other than nonsurgical maintenance care would be required, and the treatment outcome 
would therefore be regarded as successful.  
 
 
 
2.0 
SUMMARY AND STUDY RATIONALE 
 
The present study was designed to demonstrate the EFFICACY OF EASY GRAFT CLASSIC FOR 
THE TREATMENT OF PERI-IMPLANTITIS.  
 

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Easy-graft® CLASSIC, is commercially available alloplastic bone graft granules consists of 
pure β -TCP, which has been commonly used for the indication of ridge preservation17, 18, 
peri-implant bone augmentation19, sinus elevation20 and other treatment of intraoral / 
maxillofacial osseous defects21. It has unique handling capacity based on an extremely thin 
coating of the graft granules with poly(lactic-co-glycolic acid) (PLGA).  PLGA is used as a raw 
material to manufacture dental membranes, suture materials and resorbable screws. 
Before application, the granules are mixed with BioLinker® which consists of water and N-
Methyl-2-pyrrolidone (NMP). It is non-volatile solvent which has been in used in various 
medical products for more than 10 years. Easy-graft remains moldable until it comes in 
contact with blood or tissue fluids. When the material is soaked in blood in bone defects it 
hardens in a few minutes to form stable porous scaffold for bone regeneration. This 
characteristic of graft material gives better handling for the clinician. 
 
Regenerative treatment of peri-implantitis lesions can be performed in cases with 
considerable pocket formation and bone loss after the acute infection has been resolved 
and proper oral hygiene has been instituted.  Reported clinical studies indicate that 
 
17 Leventis MD, et.al. (2016)  Minimally invasive alveolar ridge preservation utilizing an in situ hardening β-tricalcium phosphate 
bone substitute. A multicenter case series. Int J Dent. ID 5406736 
18 Schneider D, et.al. (2014) Labial soft tissue volume evaluation of different techniques for ridge preservation after tooth 
extraction: a randomized controlled clinical trial. J Clin Periodontol. 41(6): 612-617.  
19 El Sayed et. al. (2015) After socket preservation of upper anterior teeth.  Alexandria Dental Journal. 40: 79-85 
20 Troedhan A, et.al. (2015) Biomechanical Stability of Dental Implants in Augmented Maxillary Sites: Results of a Randomized 
Clinical Study with Four Different Biomaterials and PRF and a Biological View on Guided Bone Regeneration. BioMed Res Int.  ID 
850340 
21 Neumeyer S. et al. (2010) The use of polylactide-coated ß-TCP: Closure of oro-antral communications.  Implants.  4:32-36 
 

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Page 13 of 63  
considerable bone regeneration and re-osseointegration can be obtained by using various 
types of bone graft materials and membranes. Meta-analysis of latest systematic literature 
review22 revealed that the weighted mean of marginal bone level change was 1.97 mm, PD 
reduction was 2.78 mm and BOP reduced by 52.5% by treatment with regenerative 
treatment. However, a different compatibility between bone grafting material and 
chemically and mechanically decontaminated implant surface might bring a different clinical 
outcome.  The purpose of  the study is to assess the effectiveness of in-situ hardening β -
TCP material, easy-graft CLASSIC, for the regenerative treatment of peri-implantitis with 
polylactide based biodegradable membrane (GUIDOR® Bio-resorbable Matrix Membrane) 
following clinically adequate decontamination procedures.   
 
The day of surgery will be designated as Day 0.  Subjects will have periodontal surgery based 
on the protocol of Guided Bone Regeneration. Subjects will have a guided bone 
regeneration surgery with GUIDOR® Bio-resorbable Matrix Membrane and Easy graft classic 
for the implants experiencing peri-implantitis. The surgical side will be assessed for osseous 
and implant surface anomalies. Intraoperative and postoperative measurements will be 
made and the flap will be closed with sutures. 
 
 
22 Daugela P, et al. (2016) Surgical regenerative treatment for peril-implantitis: Meta-analysis of recent findings in a systematic 
literature review. J Oral Maxillofac Res. 9 (3): e15 
 

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The preliminary phase of the study will comprise completion of medical and dental 
histories, signing of consent forms, obtaining radiographs and photographs, performing 
screening assessments to confirm eligibility, and instruction in oral hygiene techniques.  
Before the periodontal surgical procedure, subjects may undergo plaque removal, then root 
planing and scaling to the areas to be treated, if such treatment is indicated.  The final 
esthetic outcome of the treated sites will be evaluated by the patients using the Visual 
Analog Scale (VAS) ranging from “Very Unsatisfied” to “Very Satisfied” (before and after 
viewing baseline photos). Other clinical assessments will include: subject pain/discomfort 
questionnaire, change in probing depth, change in clinical attachment level, change in width 
of keratinized tissue from baseline to 6 and 12 months and change in radiographic bone 
gain and pathology.  Digital photographs will be obtained at each study visit and 
radiographs of the test sites will be made at the baseline, 6 and 12 month visits.   
The primary efficacy parameters will include: 
 
• 
Esthetic satisfaction from baseline to six months of all treated areas, as assessed by 
both the examiner and the subject using the Visual Analog Scale (VAS), prior to and 
after viewing baseline photos 
• 
Subject pain/discomfort questionnaire 
• 
Change from baseline in probing depth (PD) measured from the mucosal margin to 
the bottom of the probeable pocket 

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• 
Gingival recession (Rec) measured from the implant platform (IP) to the mucosal 
margin 
• 
Change from baseline visit in clinical attachment level (CAL) measured from IP to the 
bottom of the probeable pocket 
• 
Change from baseline in width of the keratinized tissue (KT) 
• 
Change from baseline in radiographic a) bone gain; b) pathology 
 
INVESTIGATIONAL DEVICE  
 
GUIDOR® easy-graft® CLASSIC 
GUIDOR® easy-graft® CLASSIC is bone grafting system contains: syringe containing beta-
tricalcium phosphate (β-TCP) granules coated with poly (lactide-co-glycolide) (PLGA) and 
ampule containing BioLinker® Activator (N-methyl-2-pyrrolidone and water). 
Easy-graft CLASSIC is a bio-resorbable, synthetic, porous bone graft substitute. It consists of 
two components: granules (supplied in syringe) and BioLinker activator (supplied in ampule).  
After mixing the components together, easy-graft CLASSIC forms a moldable mass that can be 
applied directly from the syringe into the bone defect. Easy-graft CLASSIC hardens in contact 
with body fluids, allowing a working time of approximately one minute after application into 
the bone defect.  Easy-graft CLASSIC is provided in the particle size of 500 – 1000 μm.  The 
scaffold  is a biocompatible and osteoconductive that allows for complete resorption by the 

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Page 16 of 63  
body.  β-TCP and PLGA are derived from synthetic raw materials.  Easy-graft CLASSIC comes 
sterilized via gamma irradiation. 
 
GUIDOR® Bio-resorbable Matrix Barrier 
GUIDOR® Matrix Barrier are made of polylactic acid with a citric acid ester.  It is double-
layered; the external layer has large rectangular perforations which face the overlying soft 
tissues and permit connective tissue infiltration, while the inner layer has small circular 
perforations which face bone and inhibit fibrous tissue ingrowth.  It maintains its barrier 
function for 6 weeks at least, with complete resorption occurring by 6 months.  Available 
membrane dimensions are 15 mm x 20 mm or 20 mm x 28 mm. The membrane is provided in 
a transparent plastic tray in a sealed aluminum pouch.  It comes sterilized via e-beam. 
 
3.0 
STUDY DESIGN 
 
3.1 
Overall Study Design 
This study will be case series, with two periodontists and an examiner. Both of the 
periodontists will perform surgical procedures and record surgical measurements. The 
blinded examiner will perform all other clinical assessments. 15 subjects will be enrolled.  
Written informed consent will be obtained from each subject prior to any study related 
procedures. 

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The study will follow subjects for safety and efficacy for 6 and 12 months after their surgical 
treatment.   
Screening will take place no more than 32 days prior to the first treatment and will include 
the clinical assessments required to confirm eligibility.  Clinical photograph, radiographs of 
the implant treated, clinical measurements will be taken and recorded (Pocked Depth, 
Mucosal Recession, Clinical Attachment Level). Two to four (2-4) weeks prior to the first 
study treatment, subjects may undergo plaque removal and root planing and scaling to the 
areas to be treated, if appropriate. Also, they will receive personalized oral hygiene 
instructions to reach full-mouth plaque score (FMPS) <20% and full-mouth bleeding score 
(FMBS) <20%, which will be considered requirement for surgery to occur.  
The day of surgery will be designated as Day 0. Subjects will have peri-implant regeneration 
surgery. 
If possible, implant crown will be removed with attention not to damage it. Healing screw 
will be placed on the implants. Upon flap elevation and debridement of the peri implant 
lesion, the operator will record the type of bony defect associated to the treated implant 
(see Inclusion criteria 3). Titanium Implant surface will be debrided with rotating burs and 
brushes 
(PERI-SET 
Swden&Martina 
Inc.), 
and 
decontaminated 
with 
EDTA 
gel 
(Straumann® PrefGel. pH neutral, 24% EDTA) for 2 minutes and with the alternation of 
Perio-Flow Chlorhexidine mouthwash (GUM® ParoEx®, Chlorhexidine Gluconate Oral Rinse 
USP 0,12%, SUNSTAR) saline water and H2O2 using cotton pellets. After the completion of 
these procedures, Easy-graft® CLASSIC will be placed to fill the peri-implant defect. 

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GUIDOR® Bio-resorbable Matrix Membrane will be placed on top of the easy-graft classic. If 
the implant crown was successfully removed and healing screw placed, the implant will be 
covered by the flap and submerged. Intraoperative and postoperative measurements will 
be made and the flap will be closed with sutures. Patients will be instructed to take 500 mg 
of amoxicillin three times a day for 7 days, starting at least one hour prior the procedure.  
Fifteen (15) male or female subjects, aged 21 to 85 years, will be recruited for the study 
from existing patient databases, as well as, from screenings of volunteers responding to 
advertisements, if necessary.  
 
 
Objectives 
The objectives of this study are to assess the EFFICACY OF EASY GRAFT CLASSIC FOR THE 
TREATMENT OF PERI-IMPLANTITIS. 
 
3.2.1 Primary Efficacy Endpoints 
• 
Change from baseline in probing depth 
• 
Change from baseline in clinical attachment level  
• 
Change from baseline in width of the keratinized tissue  
• 
Change from baseline in radiographic a) bone gain; b) pathology 
• 
Esthetic satisfaction from baseline to six months of all treated areas, as assessed by 
both the examiner and the subject using the Visual Analog Scale (VAS), prior to and 
after viewing baseline photos 

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Page 19 of 63  
• 
Subject pain/discomfort questionnaire 
 
3.2.2 Study Duration 
The duration of this study is to be twelve (12) months following the surgical procedure. 
 
3.2.3 Study Timeline Summary 
 
Screening 
Baseline 
and Surgery 
Post 
Treatment 
Evaluation 
Post 
Treatment 
Evaluation 
Post 
Treatment 
Evaluation 
Post 
Treatment 
Evaluation 
Post 
Treatment 
Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Within 
32
days 
 of surgery 
Day 0 
 Week 1 
± 3 days 
Month 1 
±7 days 
Month 3 
± 14 days 
Month 6 
± 14 days 
Month 12 
± 14 days 
 
3.2.4 Safety Endpoints 
Assessments of subject safety will include a tabulation of the incidence of adverse events.  
All treatment-related adverse events that occur up to 30 days excepting surgery related AEs 
within 48 hours after any treatment will be recorded, and all serious adverse events 
throughout the study will be recorded.   

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Page 20 of 63  
 
3.3 
Subject Eligibility 
 
3.3.1 Inclusion Criteria 
 
Subjects must meet the following inclusion criteria to be eligible for the study:   
 
1. Subject has read and signed the IRB approved consent form before treatment. 
2. Subject must be age 21 or above. 
3. Subject must be willing and able to follow study procedures and instructions. 
4. Subject affected by moderate to severe peri-implant disease*.  
5. Treated chronic periodontitis and proper periodontal maintenance care,  
Dental implant must meet the following criteria to be selected for the study: 
1. Implant presenting PD ≥ 6 mm 
2. Radiographic implant bone loss more than 25% of the implant length (Apex of the implant 
to implant platform)23. 
3. Peri implant bone defect being a buccal dehiscence and semicircular bone resorption to the 
middle of the implant body, buccal dehiscence and circular bone resorption with lingual 
bone plate intact or circular bone resorption with buccal and lingual bone plates intact  
 
23 Froum SJ, Rosen PS. A proposed classification for peri-implantitis. Int J Periodontics Restorative Dent. 2012 Oct;32(5):533-40. 

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Page 21 of 63  
4. Single tooth implant restoration or implant supported fixed partial denture. 
 
 
3.3.2 Exclusion Criteria 
 
Subject with any of the following will not be eligible for the study: 
• Subjects participating (currently or within 30 days prior to enrollment) in other clinical 
trials involving therapeutic intervention (either medical or dental). 
• Subjects with poor oral hygiene as indicated by a score of greater than 50% on the 
O’Leary Plaque Index. 
• Subjects with a systemic condition, which would preclude periodontal treatment, 
including but not limited to uncontrolled diabetes. 
• Subjects with acute infectious lesions in the areas intended for treatment. 
• Subjects taking chronic (i.e., > 2 weeks), therapeutic doses of medications known to 
affect 
bone 
metabolism 
such 
as 
nonsteroidal 
anti-inflammatory 
drugs 
or 
bisphosphonates.  Prophylactic aspirin (≤ 325 mg q.d.) for cardiovascular indications will 
be permitted in subjects. 
• Female subjects who are pregnant or lactating, or sexually-active female subjects who 
are of childbearing potential and are not using hormonal or barrier methods of birth 
control. (except for when a result of pregnancy test is negative) 
• Subjects who are on any chronic antibiotic or steroidal therapy. 

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• Smoker using more than 10 cigarettes or equivalent per day. 
• Smoker using cigar, smokeless tobacco use or e-cigarette. 
• Subjects diagnosed with drug induced gingival hyperplasia (e.g. calcium channel 
blockers). 
• Subjects with radiographic evidence of pathology in other areas of the mouth besides 
implant area to be treated. 
• Implant mobility. 
• Subjects with parafunctional habits and not wearing bite guard. 
•  
 
3.3.3 Investigator Training and Qualification 
The investigator(s) will be trained before participation in the study during a site initiation by 
means of a detailed description of all study procedures including the methods of obtaining 
study endpoints (measurements).  The examiner will be calibrated so that the difference is 1 
mm or less between his or her measurements and the principal investigator.  Each examiner 
will measure the recession depth on two subjects three times each during each calibration 
session.  These measurements will be recorded on a case report form and analyzed to 
ensure each examiner’s accuracy is 1 mm or less.  Examiner recalibration will be performed 
at the six month follow-up visit to ensure that his or her accuracy in measuring recession 
depth remains within that limit.  Any examiner who has greater than 1.0 mm variability 

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Protocol Number:  CUSD2 
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Original Issue Date: January 6th 2017 
 
 
Page 23 of 63  
from the principal investigator will undergo retraining by the principal investigator, as 
necessary. 
 
One examiner will make all the measurements for each subject.  The investigator 
guarantees that the examiner, who has working experience with the probe, is well qualified.  
All investigators will be noted on the Investigator’s Agreement and appropriate 
qualifications (CV and license) will be maintained in the investigator file.   
 
3.3.4 Blinding and Probe Calibration  
All study staff, with the exception of the treating clinician will be blinded to the treatment 
administered.  Only calibrated UNC 15 probes will be used. 
 
3.4 
Study Procedures 
 
3.4.1 Pre-Operative Treatment 
Medical examination and past history as well as dental examination and past history will 
be completed at this stage.  
Within 32 days prior to surgery, the subject will undergo plaque removal and the test sites 
will be undergo to root planing and scaling (if determined to be appropriate treatment by 
the investigator). Two to four (2-4) weeks prior to the first study treatment, subjects may 
undergo plaque removal and root planing and scaling to the areas to be treated, if 

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Periodontics  
Protocol Number:  CUSD2 
Revision: October 22nd 2018 
Original Issue Date: January 6th 2017 
 
 
Page 24 of 63  
appropriate. Also, they will receive personalized oral hygiene instructions to reach full-
mouth plaque score (FMPS) <20% and full-mouth bleeding score (FMBS) <20%, which will 
be considered requirement for surgery to occur. 
 
3.4.2 Study Treatments 
Screening will take place no more than 32 days prior to the first treatment and will include 
the clinical assessments required to confirm eligibility.  Informed Consent Form will be 
signed at Screening Visit (Visit 1). Clinical photograph, radiographs of the implant treated, 
clinical measurements will be taken and recorded (Pocked Depth, Mucosal Recession, 
Clinical Attachment Level). 
The day of surgery will be designated as Day 0. Subjects will have peri-implant regeneration 
surgery. 
Whenever possible implant crown will be removed and cleaned. Healing screw will be 
placed on the implant. Upon flap elevation and debridement of the peri implant lesion, the 
operator will record the type of bony defect associated to the treated implant (see Inclusion 
criteria 3). Titanium Implant surface will be debrided with rotating burs and brushes (PERI-
SET, Sweden&Martina Inc.), and decontaminated with EDTA (PrefGel: Straumann) for 2 
minutes and with the alternation of Perio-Flow Chlorhexidine mouthwash (GUM® ParoEx®, 
Chlorhexidine Gluconate Oral Rinse USP 0,12% SUNSTAR), saline water and H2O2 using 
cotton pellets. After the completion of these procedures, Easy-graft® CLASSIC will be placed 
on the peri-implant defect surface. GUIDOR® Bio-resorbable Matrix Membrane will be 

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Protocol Number:  CUSD2 
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Original Issue Date: January 6th 2017 
 
 
Page 25 of 63  
placed on top of the easy-graft classic and stabilized. If the implant crown was successfully 
removed, flaps will be primary closed and the implant will be covered completely. Second 
stage, minimally invasive surgery to gain access to the implant will be performed at 6 
months. Intraoperative and postoperative measurements will be made and the flap will be 
closed with sutures. Patients will be instructed to take 500 mg of amoxicillin three times a 
day for 7 days, starting at least one hour prior the procedure.  
 Fifteen (15) male or female subjects, aged 21 to 85 years, will be recruited for the study 
from existing patient databases, as well as, from screenings of volunteers responding to 
advertisements, if necessary.  
 
3.4.3 Other Therapy 
No other dental therapies are permitted in conjunction with the study treatments, dental 
emergencies excluded (i.e. Acute abscesses, Pulpitis, tumors or oral lesions). 
 
3.4.4 Postsurgical Care  
Patients will be instructed to take 500 mg of amoxicillin three times a day for 7 days, 
starting at least one hour prior the procedure. In case of allergy to amoxicillin, patient will 
assume 300mg Clindamycin three times a day for 7 days. Subjects will be advised to follow 
good oral hygiene habits in all non-study sites by brushing twice daily using a soft bristled 
toothbrush, and flossing once per day.  All subjects will be instructed to avoid brushing and 
avoid the use of interdental cleaning devices for the first seven days following the surgical 

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Page 26 of 63  
procedure.  In addition, all subjects will be instructed to avoid chewing directly on the test 
sites and to avoid trauma to the test sites for the first week following the surgery.  During 
that interval, the subjects will be instructed to rinse twice daily after meals with 0.12% 
chlorhexidine gluconate non-alcohol oral rinse.  After the first week, the subjects will be 
instructed to resume gentle tooth brushing and interdental cleaning with dental floss and 
continue the 0.12% chlorohexidine gluconate oral rinse for the first 4 weeks following 
surgery. All subjects will receive local implant cleaning  at the month 3, 6 and 12  follow up 
visits. 
 
3.4.5 Management of Post-Surgical Oral Pain 
Any pre-surgical pain medications should be recorded and noted as such (i.e. pre-surgical 
pain medication).  Post-surgical pain can be divided into mild, moderate, and severe levels 
and requires a subjective assessment by the periodontists based on knowledge of the 
surgical procedure performed and the presenting signs and symptoms of the subject.  Pain 
as a secondary outcome to an adverse event, such as infection, is to be excluded if pain is an 
expected outcome of such events.  Treatment of the pain is usually the best indicator of 
pain intensity. 
MILD (Over-the Counter) 
 
Acetaminophen 250 or 500 mg. 
Products include:  Tylenol®, Datril®, Anacin®3 
 
Ibuprofen 

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Page 27 of 63  
Products include:  Motrin® 800 mg 
MODERATE (Prescription Only) 
 
Tylenol® No. 3 (codeine and acetaminophen) 
 
Vicodin® (hydrocodone 5 mg and acetaminophen 500 mg) 
 
Vicodin ES® (hydrocodone 7.5 mg and acetaminophen 750 mg) 
 
Lortab® (hydrocodone 5 mg, 7.5 mg, 10 mg and acetaminophen 500 mg) 
 
SEVERE (Prescription Only) 
• 
Demerol® 50 mg (Meperidine)* 
• 
Percocet® or Tylox® (oxycodone 5 mg and acetaminophen 500 mg)* 
*Triplicate prescription where applicable 
 
3.4.6 Post-surgical Control, Professional Tooth Cleaning , Maintenance Care.  
 
The objective of the post-operative appointments for professional tooth cleaning is both the 
removal of plaque and staining from the treated areas and the monitoring of the healing 
events.  Post-surgical controls and professional tooth cleaning will be performed at s 3, 6 
and 12 months post-surgical. At these appointments, the conditions of the soft tissue at the 
treated sites will be evaluated.  The overall level of oral hygiene will be evaluated and 
reinstruction will be given as needed at all visits. 
 
Instructions on post-operative care will be repeated at each appointment.  In particular, the 
following points should be covered during the first month: (1) continue chlorhexidine rinses 

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Protocol Number:  CUSD2 
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Page 28 of 63  
(from surgery to four weeks post-op); (2) resume gentle brushing; and (3) avoid vigorous 
chewing on, or trauma to, the treated areas. 
 
At week 6, subjects will be instructed to gradually resume interproximal cleaning, as well as 
chewing, in the treated areas.  All subjects will be maintained by full mouth professional 
prophylaxis and calculus removal once every three months, excluding surgical sites which 
will be maintained supragingivally. 
 
All treatment-related adverse events that occur up to 30 days excepting surgery related AEs 
within 48 hours after any treatment will be recorded in CRFs, and all serious adverse events 
throughout the study will be recorded.   
 
3.5 
Clinical Assessments 
 
3.5.1 Summary of Clinical Assessments 
All examinations and measurements will be performed in accordance with the Schedule of Events. 
Data will be collected and assessments will be made on study sites treated. 
 
3.5.2 Primary Efficacy Assessment 
• Esthetic satisfaction from baseline to 6 and 12 months of all treated areas, as assessed by both 
the examiner and the subject using the Visual Analog Scale (VAS), prior to and after viewing 
baseline photos 
• Subject pain/discomfort questionnaire 

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• Change from baseline in probing depth 
• Change from baseline visit in clinical attachment level  
• Change from baseline visit in width of the keratinized tissue  
• Change from baseline in radiographic a) bone gain; B) pathology 
 
3.5.3 Probing Depths  
Clinical probing depths of the periodontal sulcus will be measured using the a UNC 15 periodontal 
probe.  Measurements will be performed without local anesthesia at six (6) locations around each 
study tooth.  The number of additional locations to be measured around each experimental site will 
be determined by the extent and morphology of the area.  Interproximal pocket depths will be 
recorded at the deepest point probable at the contact points from both buccal and lingual aspects.  
Buccal and lingual pocket depth measurements will be recorded at the mid-buccal and mid-lingual 
sites.  All pocket depth measurements will be rounded down to the nearest mm and recorded.  In 
conjunction with recording the pocket depths, any bleeding from the periodontal pockets will be 
indicated by marking an asterisk on the figure recorded for the depth measurement for that same 
pocket.   
 
3.5.4 O’Leary Plaque Index 
The plaque index is determined by scoring the percentage of individual tooth surfaces with plaque.  
The following procedure will be followed: 
 
Apply disclosing solution to all exposed tooth surfaces. 

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Rinse to remove any excess solution. 
 
Examine each tooth surface (mesial, distal, facial, lingual) at the dento-gingival junction for 
presence of plaque. 
 
Presence of plaque at the dento-gingival junction is indicated by making a dash in the 
appropriate spaces on the plaque control record diagram (see Figure 1). 
 
If a tooth is missing, draw a line through the tooth on the diagram.  Missing teeth should not be 
counted in the total number of surfaces scored. 
 
Calculate the plaque index by dividing the number of surfaces with plaque by the total number 
of surfaces scored, and then multiply by 100 to obtain a percentage. 
Figure 1 Plaque Control Record 
 
3.5.5 Laboratory Assessments 
The following laboratory assessments will be conducted at screening:  
 Urine pregnancy test (females of child-bearing potential only) 

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3.6 Schedule of Investigational Events 
 
3.6.1 Screening Visit (Visit 1) 
At the screening visit the following procedures and assessments will be performed within 32 days 
prior to surgery: 
• Informed Consent 
• Subject registration  
• Medical history collection and physical examination: 
• Record of past therapy 
• Urine pregnancy test (females of child-bearing potential only) 
• Medications 
• Dental history collection 
• Record of past therapy 
• Screening assessments to determine eligibility:  
• O’Leary Plaque Index 
• Probing depths  
• Implant mobility, 
• Clinical attachment level 
• Obtain baseline radiographs of study sites  
• Dental cleaning  

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• Oral hygiene instruction 
• Supragingival plaque control, as appropriate 
• Examiner and subject baseline esthetic satisfaction VAS assessments 
• Radiographs of all target study sites  
 
 
3.6.2 Baseline/Treatment (Visit 2) 
Visit 2 may occur concurrently with Visit 1.  If separate visits are to occur, Visit 2 must occur within 
32 days of the screening examine. 
• Examiner calibration (for first 2 subjects enrolled only) 
• Preoperative and Intraoperative digital photographs 
• Concomitant medications 
• Surgical procedure 
• Post-operative instructions 
• Collection of any Adverse Events 
 
3.6.3 Post op - Week 1 (Visit 3) 
• An Investigator will rate and record the judgment of healing 
• Study personnel will obtain clinical photographs of surgical sites taking care not to place apical 
tension on flap 

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Original Issue Date: January 6th 2017 
 
 
Page 33 of 63  
• Post-operative instructions (e.g. Chlorhexidine rinse) and pain management according to 
standard procedures 
• Complete Pain Rating Scale 
• Rate and record color and texture of treated areas 
• Adverse event review 
• Concomitant medication review 
• Suture removal according to healing  
• Measurement of width of keratinized tissue 
• Pain Medication review 
 
3.6.4 Post op – 1 Month (Visit 4) 
• Rate and record the color and texture of treated areas 
• Digital photographs 
• Rate and record judgment of healing 
• Clinical attachment level 
• The examiner and subject esthetic satisfaction VAS assessments (before and after viewing 
baseline photos)  
• Supragingival plaque control as indicated 
• Oral hygiene instruction 
• Complete pain rating scale 
• Concomitant medications 

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Page 34 of 63  
• Collection of Adverse Events 
• Pain medication review 
 
3.6.5 3-Months Follow up (Visit 5) 
At the month 3 visit (Day 90 ± 14 days) the following procedures and assessments will be 
performed: 
• Rate and record the color and texture of treated areas 
• Digital photographs 
• Rate and record judgment of healing 
• Measurement of width of keratinized tissue 
• Clinical attachment level 
• The examiner and subject esthetic satisfaction VAS assessments (before and after viewing 
baseline photos)  
• Supragingival plaque control as indicated 
• Oral hygiene instruction 
• Complete pain rating scale 
• Concomitant medications 
• Collection of Adverse Events 
• Pain medication review 
• Implant area professional cleaning 
 

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3.6.6 6 Months Follow up. (Visit 6) 
Subjects will return to the clinic for a study visit 6  months (± 14 days) after surgery.  The following 
procedures and assessments will be performed at this visit: 
• Digital photographs 
• Radiographs of all treated sites 
• The examiner and subject esthetic satisfaction VAS assessments (before and after viewing 
baseline photos) 
• Rate and record the color and texture of treated areas 
• Rate and record judgment of healing 
• Measurement of width of keratinized tissue 
• Clinical attachment level 
• Supragingival plaque control as indicated 
• Oral hygiene instruction 
• Complete pain rating scale 
• Concomitant medications 
• Probing depth 
• Collection of Adverse Events 
• Pain medication review 
• Adverse Events review 
• Implant area professional cleaning 
 

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Original Issue Date: January 6th 2017 
 
 
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3.6.7  12 Months Follow up. (Visit 7) 
Subjects will return to the clinic for a study visit 6  months (± 14 days) after surgery.  The following 
procedures and assessments will be performed at this visit: 
• Digital photographs 
• Radiographs of all treated sites 
• The examiner and subject esthetic satisfaction VAS assessments (before and after viewing 
baseline photos) 
• Rate and record the color and texture of treated areas 
• Rate and record judgment of healing 
• Measurement of width of keratinized tissue 
• Clinical attachment level 
• Supragingival plaque control as indicated 
• Oral hygiene instruction 
• Complete pain rating scale 
• Concomitant medications 
• Probing depth 
• Collection of Adverse Events 
• Pain medication review 
• Adverse Events review 
• Implant area professional cleaning 
 

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Protocol Number:  CUSD2 
Revision: October 22nd 2018 
Original Issue Date: January 6th 2017 
 
 
Page 37 of 63  

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3.7 Summary of Clinical Assessments (revised by UoC to meet assessment for implant tooth) 
All examinations and measurements will be accomplished in accordance with the Schedule of 
Procedures (See Study Flowchart).  
 
Oral Hygiene Status 
 
Plaque recorded as present (1) or not present (0) on buccal and lingual surfaces of study teeth only 
 
 
 
Bleeding following Angulated Probing 
 
Bleeding will be registered at the surgical sites by means of pulling a probe with 60° angle to the 
root surface along the gingival margin. 
 
 
 
Probing Pocket Depth 
 
Distance of probe penetration (UNC 15 periodontal probe), measured from the gingival margin to 
the bottom of the probable pocket of the buccal surface to the nearest 0.5 mm. 
 
 
 
Probing Proximal Pocket Depth 
 

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Distance of probe penetration (UNC 15 periodontal probe), measured from the gingival margin to 
the bottom of the probable pocket of the mesial and distal surface to the nearest 0.5 mm. 
 
 
 
Clinical Attachment Level (CAL) 
 
Distance of probe penetration (UNC 15 periodontal probe) measured from fixed reference point to 
the nearest 0.5 mm. 
 
 
 
Proximal Probing Attachment Loss 
 
Distance of probe penetration (UNC 15 periodontal probe) measured from fixed reference point at 
the mesial and distal aspect of the tooth to the nearest 0.5 mm. 
 
 
 
Recession Depth 
 
The distance between the fixed reference point  and the soft tissue margin, measured to the 
nearest 0.5 mm with a UNC 15 periodontal probe.  At the 6 and 12 month visit, tissue coronal to 
the fixed reference point will be recorded as a negative measurement 

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Width of Keratinized Tissue 
 
The distance between the free gingival margin and the muco-gingival junction, measured to the 
nearest 0.5 mm with a graded periodontal probe.  To facilitate the identification of the muco-
gingival line, a probe may be used horizontally to move the mucosa in a coronal direction, creating 
a fold at the muco-gingival junction.  Shiller’s Iodine Solution may also be used to identify the 
muco-gingival junction 
 
 
 
Examination of Defects During Surgery 
 
After the flaps have been raised and the area debrided, characterization of the morphology and 
measurements of the defects are made, with the UNC 15 periodontal probe, and recorded as 
follows: 
Alveolar Bone Level (Before and after osteoplasty if needed) 
 
 
 
Notation of intra marrow penetration  of alveolar crest 
 
Notation of alveolar crest topography and whether osteoplasty was to be performed to refine 
contours. 
 

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Clinical Photographs 
 
Clinical photographs will be taken of each tooth involved in the study before, during and after 
surgery, at Weeks 1, and 6 post surgery and at the 3, and 6 month follow-up examinations.  
  
 
 
Post-Op Discomfort and Satisfaction Questionnaires 
 
 
The subject’s satisfaction with respect to postoperative discomfort between test and  
 
control quadrants will be evaluated by asking the subject about pain, bleeding, 
 
 
swelling and sensitivity using 10 cm visual analogue scale (See Appendix 1).

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Procedure/ Assessment 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Screen 
0-32 Days 
Prior 
Surgery 
 
Day 0 
 
Post-op 
Day 7 
 
1 Month 
42± 7 Days 
 
Month 3 
90± 14 Days 
 
Month 6 
±14 Days 
 
Month 12 
±14 Days 
 
Informed Consent 
X 
 
 
 
 
 
 
Eligibility/ Study Lesion Identification, 
Subject Registration 
X 
 
 
 
 
 
 
Demographics/Dental/Medical History 
X 
 
 
 
 
 
 
O’Leary Plaque Index 
X 
 
 
 
 
X 
X 
Probing Depths 
X 
 
 
 
 
X 
X 
Pregnancy Test 
X1 
 
 
 
 
 
 
Radiographic Exam 
X 
 
 
 
 
X 
X 
Dental Cleaning 
X 
 
 
 
X 
X 
X 

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Digital Photos 
 
X 
X 
X 
X 
X 
X 
Examiner and Subject GORS and VAS of 
esthetic satisfaction 
 
X 
X 
X 
X 
X 
X 
Plaque Control/Oral Hygiene Instruction 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
Clinical Attachment level 
X 
 
 
 
 
X 
X 
Examiner calibration 
 
X 
 
 
 
 
 
Easy Graft Classic surgery 
 
X 
 
 
 
 
 
Second stage surgery for submerged 
implants only 
 
 
 
 
 
X 
 
Rate and record Judgment of Healing 
 
 
X 
X 
X 
X 
X 
Pain Rating Scale 
 
 
X 
X 
X 
X 
X 
Color and Texture 
 
 
X 
X 
X 
X 
X 
Width of Keratinized Tissue 
 
 
 
X 
X 
X 
X 
1. 
 
In 
females 
of 
child-bearing 
potential 
only

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3.7 
Radiography 
Radiographs will be taken using a modified Rinn system in order to obtain radiographs with 
minimum projection error. Rinn system is a radiograph sensor holder that favors a standard 
system to have reproducible radiograph images. We will customize this holder in order to 
reproduce standard radiographic image.  Evaluable bitewings radiographs will be taken in 
each of the tooth regions included in the study. 
 
3.7.1 Exposure 
Intraoral film, 24 × 40 mm, from the same batch will be used. 
 
3.7.2 Processing 
Digital X-ray system will be used. 
 
3.7.3 Handling 
Study radiographs are stored in Axium system. 
 
3.7.4  Radiographic assessment  
 
Intra-oral biewing radiographs will be obtained at baseline, at 6 and 12 months. These 
radiographs should be taken using device to standardize during course of the study and 
should image the target tooth and at least 2 mm on either side of the osseous defect. 

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The following standardizing technique will produce repeatable diagnostic quality 
radiographs with close to identical geometry and image clarity. 
Once the exposure parameters are selected they should not be changed during the 
course of the study. Send the image files to the central reading center at each study site 
for analysis following the instructions. 
 
3.7.5  Derivation or calculation of variable 
 
Image processing software is used to capture measurements (MiPACS Dental 
Enterprise). Measurement tool will be calibrated with a 1 millimeter radiographic image.  
The measurements are taken from a stationary landmark (Distal and Mesial portion of 
implant platform -  Bdp and Bmp) to the mesial and distal bone crest of osseous defect in 
millimeters (Bda and Bma). In order to calculate percentage of bone fill (or residual 
defect) this last measured will be compared with implant length noted on the chart. 
Subsequent images are logged in and saved to the file. Linear measurements of bone 
height along root surfaces are made using the same method as the original defect.  
 
• Linear bone change (distal) = Bdp(0,6,12) – Bda(0,6,12) 
• Linear bone change (mesial) = Bmp(0,6,12) – Bma(0,6,12) 
Where (0,6,12) is the measure at baseline, 6 and 12 months. 

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3.8 
Discontinuation of Treatment 
Subjects may be withdrawn from the study prior to completion of treatment for the 
following reasons: 
• 
Subject withdrawal of consent 
• 
Investigator’s decision 
• 
Death 
• 
Poor maintenance of oral hygiene 
• 
Lack of compliance 
• 
Discontinues Orthodontics treatment and/or other treatments on study site(s) and 
adjacent teeth 
When a subject is terminated from the study prior to completion of treatment, the 
subject will continue to be evaluated as scheduled.  Attempts will be made to 
perform all follow-up assessments and procedures required by the protocol. 
 
4.0 
ADVERSE EVENTS 
 
 
Recording and Reporting Adverse Events 
An Adverse Event (AE) is defined as any untoward medical occurrence in a subject of a 
clinical investigation administered an investigational product and that does not necessarily 
have a causal relationship with this treatment.  An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 

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associated with the use of an investigational product, whether or not related to use of the 
product. 
 
Recording Adverse Events 
All adverse events occurring after surgical procedure will be collected during the entire trial.  
Each adverse event will be followed until the adverse event has resolved or stabilized.  
During visits, subjects should be encouraged to report adverse events spontaneously or in 
response to general, non-directed questioning.   
• 
Standard medical terminology for the AE and the associated body system 
• 
Description of adverse event and clinical consequences  
• 
Date and time of onset 
• 
Date and time of resolution of the adverse event  
• 
Whether or not the event is ongoing 
• 
Severity of the event  
• 
Relationship between the adverse event and the investigational agent or related 
procedure 
• 
Description of any therapy administered and associated outcome (actions required) 
• 
Outcome of the AE 
• 
Whether or not the effect was serious and/or unanticipated 
All AEs, regardless of seriousness, severity, or presumed relationship to study 
therapy, must be recorded using medical terminology in the source document and 
on the adverse event case report form.   

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Whenever possible, a diagnosis should be given when signs and symptoms are due 
to common etiology (e.g., cough, runny nose, sneezing, sore throat, and head 
congestion should be reported as “upper respiratory infection”).   
Each adverse event should be reported separately.  For example, “nausea and 
vomiting” should be recorded as two (2) separate events. 
 
 
Grading Adverse Events 
Common Terminology Criteria for Adverse Events v3.0, (on the NCI website, 
http://ctep.info.nih.gov) will be used to grade all toxicities/adverse events.  Adverse events 
not included in the CTCAE v.3.0 should be reported with common medical terminology and 
graded according to definitions in the CTC Manual. 
 
Assigning Relationship of Adverse Events to Treatment 
A relationship must be assigned by the investigator to each reported adverse event, and will 
be documented as follows: 
• 
Unrelated  
The event is clearly due to causes other than the study treatment. 
• 
Unlikely  
Toxicity is doubtfully related to the study treatment.  The event was 
 
 
most likely related to other factors such as the subject’s clinical state, 
 
 
concomitant drugs or other therapeutic interventions. 
• 
Possible  
The event follows a reasonable temporal sequence from the time of 
 
 
study treatment administration, but could have been produced by 

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other   
factors such as the subject’s clinical state, therapeutic interventions 
or  
 
concomitant drugs. 
• 
Probable  
The event follows a reasonable temporal sequence from the time of 
 
 
study treatment, and follows a known response pattern to treatment.  
 
 
The toxicity cannot be reasonably explained by other factors such as 
 
 
the subject’s clinical state, therapeutic interventions or concomitant 
 
 
drugs. 
• 
Definite 
The event follows a reasonable temporal sequence from the time of 
 
 
study treatment administration, follows a known response pattern to 
 
 
the study treatment, cannot be reasonably explained by other factors 
 
 
such as the subject’s condition, concomitant drugs or therapeutic  
 
 
interventions, AND either occurs immediately following  
 
 
 
administration of the study treatment, improves on stopping the 
study   
treatment, or reappears on re-exposure. 
 
 
Serious Adverse Events 
 
 
Definition of a Serious Adverse Event 
 
A Serious Adverse Event (SAE) is defined as any event meeting any of the following criteria: 

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• 
Is life-threatening or fatal 
• 
Requires, or significantly prolongs, inpatient hospitalization 
• 
Results in persistent or significant disability and/or incapacity 
• 
Is a congenital anomaly or birth defect 
• 
Requires medical or surgical intervention to prevent one of the outcomes listed 
above 
 
 
SAE report to Sponsor and IRB 
Investigators and other study site personnel must inform appropriate Sponsor 
representatives of any SAE that occurs during the course of the study within one day 
(i.e., immediately but no later than the end of the next business day) of when he or she 
becomes aware of it.  
 
The Sponsor representative will work with the Investigator to compile all the necessary 
information and ensure that the appropriate Sponsor personnel receives a report by day 
one for all fatal and life-threatening cases and by day five for all other SAEs. 
If an AE becomes a SAE, this and other relevant follow-up information must also be 
provided to Sponsor within one day for all fatal and life-threatening cases and by day 
five for all other SAEs. 

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The Investigator is responsible for informing the ethics committee of SAEs as per local 
requirements.  
SUNSTAR IS RESPONSIBLE FOR INFORMING THE REGULATORY AUTHORITY OF DEVICE RELATED SAES AS PER 
REQUIREMENTS. 
 
5.0 
STATISTICAL AND ANALYTICAL PLAN 
 
Intent to Treat Population 
The primary efficacy analysis and summaries will be performed on the “intent to treat” (ITT) 
population, defined as all subjects who successfully completed the screening to enter this 
trial. 
 
Safety Population  
All safety summaries and analyses will be performed on the safety population, defined to be 
all subjects.   
 
Evaluable Population 
All secondary efficacy analyses will be performed on an evaluable population, defined to be 
all subjects who received surgical treatment in accordance with the protocol.   

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Subjects exiting after undergoing surgery, but before month 6 due to treatment-related 
adverse events will be included in the evaluable population.  Subjects that do not complete 
the assessments due to satisfaction with treatment will also be included in the evaluable 
population. All attempts will be made to collect complete follow-up evaluations for these 
subjects despite study exit.  These subjects will be included in the analysis based on the 
assessments that are completed. 
Subjects will be deemed non-evaluable if they do not meet the eligibility criteria as outlined 
in the protocol.  Other reasons to be considered non-evaluable include protocol violations, 
as described below, and any actions that compromise the effectiveness of the treatment, 
for non-efficacy or safety related reasons. 
Protocol violators consist of subjects who do not comply with the protocol in terms of 
treatment administration, visit timing, and/or assessment compliance.  Each protocol 
violation will be discussed between Investigators and the Sponsor to evaluate the impact on 
the statistical assessment before performing the analyses. 
Missing Data 
It is not anticipated that many subjects will exit the study prematurely or will miss visits. The 
reasons for early termination, along with the timing of the early terminations will be 
provided.   
Subjects missing a baseline evaluation will be discussed between Investigators and the 
Sponsor to evaluate the impact on the statistical assessment before performing the 
analyses  

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Assessment of Safety 
Adverse events with an onset within 30 days of any surgical treatment will be recorded and 
tabulated.  All adverse events will be tabulated by first occurrence of the event, maximum 
severity, and strongest relationship to study treatment by body system. 
 
6.0 
REGULATORY AND ADMINISTRATIVE REQUIREMENTS 
 
6.1 
IRB Requirements   
United States Federal regulations require that all investigational studies be conducted 
under the auspices of an Institutional Review Board (IRB), as defined in the Code of Federal 
Regulations, Title 21, Part 56.  This committee, the makeup of which must conform to the 
Federal, State and local guidelines regarding such, will approve all aspects of the Study, 
including said Protocol and Informed Consents to be used, prior to initiation.  The formal 
written approval notice must be signed by the chairman or authorized designee and must 
identify the specific protocol.  In cases where an IRB member has a conflicting interest, 
abstention of that individual from voting should be documented.  The investigator will 
provide the sponsor with a copy of the communication from the Committee to investigator 
indicating approval of the protocol and consent form.  All changes to the protocol and 
consent form must be reviewed and approved prior to implementation, except where 
necessary to eliminate apparent immediate hazards to human subjects. 

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The investigator must also report to the IRB, at least annually, on the progress of the 
investigation.  Continuing IRB review should be documented by a letter from the IRB.  
Notification to the IRB by the investigator within three months after completion, 
termination, or discontinuation of the study at the specific site must be documented. 
 
6.2 
Protocol Amendments 
Amendments will originate from the sponsor and will be provided to the investigator for 
submission to his or her IRB for its review and approval prior to implementation.  It should 
be noted that when an amendment to a protocol substantially alters the study design or 
increases potential risk to the study subject, the informed consent should be revised and if 
applicable, subject’s consent to continue participation should again be obtained. 
No deviations from the protocol should be made except in emergency situations where 
alternative treatment is necessary for the protection, proper care and wellbeing of subjects.  
In situations requiring a departure from the protocol, the investigator or other physician in 
attendance will contact the sponsor’s clinical representative by fax or telephone.  If 
possible, this contact will be made before implementing any departure from the protocol.  
In all cases, contact with the sponsor’s clinical representative must be made as soon as 
possible in order to discuss the situation and agree on an appropriate course of action.  The 
case report form and source document will describe any departure from the protocol and 
the circumstances requiring it. 
 

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6.3 
Informed Consent 
In accordance with the Code of Federal Regulations, Title 21, Part 50.20 the investigator will 
be responsible for obtaining an Informed Consent, signed by the subject or legally 
authorized representative, from every subject prior to his/her participation in the study.  
The consent form that is used must be the current version and must be approved by both 
the reviewing IRB and by the sponsor.  Informed consent will be obtained from the subject 
after a full explanation of the purpose of the study, risks and discomforts involved, potential 
benefits, etc. have been provided by the investigator both verbally and in writing.  The 
original signed copy of the informed consent must be maintained in the institution’s 
records, and is subject to inspection by a sponsor representative. 
 
 
 

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APPENDIX I: QUESTIONNAIRES/SURVEYS 
 
1. 
 
Examiner’s Judgment of Healing 
2. 
 
Pain Visual Analogue Scales 
3. 
 
Discomfort and Satisfaction Questionnaire 
4. 
 
Color and Texture Scale 
5. 
 
Inflammation Score 

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EXAMINER’S JUDGMENT OF HEALING 
(circle response) 
 
Upper Right Quadrant:    
 
Much worse 
than expected 
Worse than 
expected 
As Expected 
Better than 
expected 
Much better 
than expected 
 
 
 
Upper Left Quadrant:   
 
Much worse 
than expected 
Worse than 
expected 
As Expected 
Better than 
expected 
Much better 
than expected 
 
_________________________________________________________________________________ 
 
 
Lower Right Quadrant:    
 

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Much worse 
than expected 
Worse than 
expected 
As Expected 
Better than 
expected 
Much better 
than expected 
 
_________________________________________________________________________________ 
 
 
Lower Left Quadrant:  
 
Much worse 
than expected 
Worse than 
expected 
As Expected 
Better than 
expected 
Much better 
than expected 
 
_________________________________________________________________________________

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PAIN VISUAL ANALOGUE SCALES 
 
Please have patient complete the scales below by drawing a single vertical line across each scale at 
the point corresponding to the patient’s level of pain. 
 
 
 
 
 
Upper Right Quadrant    
 
 
 
___________________________________________________ 
No Pain 
 
 
 
 
 
 
 
 
 
Extreme Pain 
 
 
 
 
 
Upper Left Quadrant 
 
 
 
___________________________________________________ 
No Pain 
 
 
 
 
 
 
 
 
 
Extreme Pain 
 
 
 
 
 
Lower Right Quadrants  
 
 
___________________________________________________ 
No Pain 
 
 
 
 
 
 
 
 
 
Extreme Pain 

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Lower Left Quadrant 
 
 
 
___________________________________________________ 
No Pain 
 
 
 
 
 
 
 
 
 
Extreme Pain 
 
 
 
     DISCOMFORT & ESTHETIC SATISFACTION QUESTIONNAIRE:  Maxillae 
Category 
Right Quadrant 
Left Quadrant 
Sensitivity 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
Bleeding 
None 
Mild 
Moderate* 
Severe* 
None 
Mild 
Moderate* 
Severe* 

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Duration:__________ 
Duration:__________ 
Swelling 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
 
(*Record as Adverse Event) 
Has the patient experienced any other differences between the Left and Right Study sites? 
□ Y   □  N 
If Yes, explain:___________________________________________________________ 
Overall, how satisfied is the patient with the appearance of the study sites? 
Right Study Site 
□  Very Satisfied   □  Satisfied   □  Neither   □  Unsatisfied   □  Very Unsatisfied 
Left Study Site 
□  Very Satisfied   □  Satisfied   □  Neither   □  Unsatisfied   □  Very Unsatisfied 
If not satisfied, please explain: ______________________________________________ 
Overall, which side did the patient experience the most discomfort?  □  Right   □ Left 
 
Examiner’s signature: _________________________________Date:______________ 

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Color and texture will be scored in relation to adjacent tissues as follows: 
 
                 DISCOMFORT & SATISFACTION QUESTIONNAIRE: Mandible 
Category 
Right Quadrant 
Left Quadrant 
Sensitivity 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
Bleeding 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
Swelling 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
None 
Mild 
Moderate* 
Severe* 
Duration:__________ 
 
(*Record as Adverse Event) 

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Has the patient experienced any other differences between the Left and Right Study sites? 
□ Y   □  N 
If Yes, explain:___________________________________________________________ 
Overall, how satisfied is the patient with the appearance of the study sites? 
Right Study Site 
□  Very Satisfied   □  Satisfied   □  Neither   □  Unsatisfied   □  Very Unsatisfied 
Left Study Site 
□  Very Satisfied   □  Satisfied   □  Neither   □  Unsatisfied   □  Very Unsatisfied 
If not satisfied, please explain: ______________________________________________ 
Overall, which side did the patient experience the most discomfort?  □  Right   □ Left 
 
Examiner’s signature: _________________________________Date:______________