Alveolar Bone Loss, Periodontal Diseases
Conditions
Keywords
bone grafting, alveolar bone loss, periodontal diseases
Brief summary
GUIDOR Growth Factor Enchanted Bone Graft Substitute (GFeBGS) when used in periodontal surgery will shown greater gum and bone regeneration when compare to bone graft substitute alone. Also, to find the optimal dose.
Detailed description
This will be a prospective, randomized, double-blinded, controlled, multi-center, dose-verification clinical study in subjects who require surgical intervention to treat a qualifying periodontal defect. Subjects 25 years and older with advanced periodontal disease in at least one site requiring surgical treatment to correct a bone defect.
Interventions
DEVICEbeta-tricalcium phosphate alone
DEVICEGFeBGS 0.1%
DEVICEGFeBGS 0.3%
DEVICEGFeBGS 0.4%
Sponsors
Sunstar Americas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, age of 25 and older * Must have read, understood, and signed a consent form * Must be able and willing to follow study procedures and instructions * Must have undergone thorough scaling and root planing of the target tooth and be expected to demonstrate good plaque control after instruction in oral hygiene * The target tooth must exhibit the following: * A pocket depth of 7 mm or greater * After surgical debridement, 4 mm or greater intrabony defect with at least 1 bony wall * Sufficient keratinized tissue to allow complete tissue coverage of the defect * Radiographic base of defect at least 3 mm coronal to the apex of the tooth
Exclusion criteria
* Failure to maintain adequate oral hygiene during the screening phase * Women of child-bearing potential * A history within the last 6 months of HIV, Type IV heart disease, or end-stage renal disease * A history of oral cancer or any other cancer (exception: subjects with a history of skin cancers such as squamous and basal carcinoma with end of treatment at least 6 months ago and/or prostate cancer with end of treatment at least 5 years ago may be enrolled) * A history within 12 months of previous open flap periodontal surgery on the study tooth. * A diagnosis of pre-malignant oral lesion(s) * A traumatic occlusion of the target tooth * Target study tooth exhibiting Grade III mobility * Maxillary molars or maxillary first premolar with a prominent mesial concavity * Study tooth exhibiting a Class II or greater furcation defect * Clinical or radiographic signs of untreated acute or chronic periapical infection at the surgical site, apical pathology, root fracture, severe root irregularities, cemental pearls, cervical enamel projections not easily removed by odontoplasty, untreated carious lesions at the cemento-enamel junction (CEJ) or on the root surface, or restorations with open or otherwise defective margins at or below the CEJ * A history within the last 6 months of the daily use of any tobacco products besides cigarettes (smokeless chewing tobacco, pipe or cigar smoking), or of smoking more than 10 cigarettes per day * Subjects participating in other clinical trials within 30 days of enrollment * Subjects having uncontrolled endocrine-induced diseases (e.g. uncontrolled diabetes mellitus and hyperparathyroidism) * Subjects undergoing current therapy with systemic steroids or other drugs that significantly alter bone metabolism * Subjects with Localized Juvenile Periodontitis (LJP) sites in the oral cavity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements | 6 months post-surgery | The primary effectiveness endpoint is a composite endpoint that considers radiographic and clinical measurements at six months post-implantation: the amount of linear bone growth (LBG), which is assessed with the use of radiographs, and the regain from baseline of clinical attachment level (∆CAL), which is assessed clinically. Linear bone growth (LBG) in a vertical and horizontal direction is determined radiographically at six months post-implantation. The clinical attachment level (CAL) is the distance from the cemento-enamel junction (CEJ) (or other fixed reference point) generally along the long axis of the tooth to the deepest extent of the periodontal pocket. The success criteria are ΔCAL ≥1.5 mm and LBG ≥1 mm at 6 months after the treatment. Both the ∆CAL and LBG must meet the success criteria for a subject to be considered a success. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinical Attachment Level at 6 Months | Baseline and 6 months post-surgery | The clinical attachment level is the distance from the cemento-enamel junction (or other fixed reference point) generally along the long axis of the tooth to the deepest extent of the periodontal pocket. Change = (6 months measurement - Baseline measurement) |
| Linear Bone Growth at 6 Months | Baseline and 6 months post-surgery | Linear measurement of bone height in millimeters along mesial and/or distal root surfaces of the defect site is captured radiographically at baseline and 6 months. Linear Bone Growth = (Baseline measurement - 6 months measurement) |
| Percent Bone Fill at 6 Months | Baseline and 6 months post-surgery | Linear measurement of bone height in millimeters along mesial and/or distal root surfaces of the defect site is captured radiographically at baseline and 6 months. Percent Bone Fill is calculated by dividing Linear Bone Growth at 6 months by bone height at baseline. |
| Change in Clinical Attachment Level at 3 Months | Baseline and 3 months post-surgery | The clinical attachment level is the distance from the cemento-enamel junction (or other fixed reference point) generally along the long axis of the tooth to the deepest extent of the periodontal pocket. Change = (3 months measurement - Baseline measurement) |
| Pocket Depth Change at 6 Months | Baseline and 6 months post-surgery | Length from free gingival margin to the base of the pocket in millimeter is measured with North Carolina 15 mm periodontal probes. Pocket Depth Change = (6 months measurement - Baseline measurement) |
| Change in Gingival Recession at 3 Months | Baseline and 3 months post-surgery | Length from the free gingival margin to the CEJ is measured in millimeter with North Carolina 15 mm periodontal probes. Gingival Recession = (3 months measurement - Baseline measurement) |
| Change in Gingival Recession at 6 Months | Baseline and 6 months post-surgery | Length from the free gingival margin to the CEJ is measured in millimeter with North Carolina 15 mm periodontal probes. Gingival Recession = (6 months measurement - Baseline measurement) |
| Pocket Depth Change at 3 Months | Baseline and 3 months post-surgery | Length from free gingival margin to the base of the pocket in millimeter is measured with North Carolina 15 mm periodontal probes. Pocket Depth Change = (3 months measurement - Baseline measurement) |
Countries
United States
Participant flow
Recruitment details
Participants were recruited and enrolled at 6 dental clinical centers between November 2012 and December 2013.
Participants by arm
| Arm | Count |
|---|---|
| Beta-tricalcium Phosphate Alone beta-tricalcium phosphate + placebo vehicle | 22 |
| GFeBGS 0.1% GFeBGS consisting of beta-tricalcium phosphate + 0.1% recombinant human basic fibroblast growth factor (rh-bFGF) | 21 |
| GFeBGS 0.3% GFeBGS consisting of beta-tricalcium phosphate + 0.3% rh-bFGF | 22 |
| GFeGBS 0.4% GFeBGS consisting of beta-tricalcium phosphate + 0.4% rh-bFGF | 23 |
| Total | 88 |
Baseline characteristics
| Characteristic | Beta-tricalcium Phosphate Alone | Total | GFeGBS 0.4% | GFeBGS 0.3% | GFeBGS 0.1% |
|---|---|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 10.7 | 56.0 years STANDARD_DEVIATION 11 | 54.0 years STANDARD_DEVIATION 10.5 | 54.0 years STANDARD_DEVIATION 10.6 | 59.7 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 10 Participants | 1 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 78 Participants | 22 Participants | 19 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 9 Participants | 2 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 11 Participants | 3 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 4 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 63 Participants | 18 Participants | 14 Participants | 15 Participants |
| Sex: Female, Male Female | 9 Participants | 34 Participants | 9 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Male | 13 Participants | 54 Participants | 14 Participants | 13 Participants | 14 Participants |
| Smoking history Current smoker or smoked within past 6 months | 3 Participants | 13 Participants | 3 Participants | 4 Participants | 3 Participants |
| Smoking history Non-smoker | 19 Participants | 75 Participants | 20 Participants | 18 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 22 | 0 / 21 | 0 / 22 | 0 / 23 |
| other Total, other adverse events | 4 / 22 | 6 / 21 | 2 / 22 | 10 / 23 |
| serious Total, serious adverse events | 2 / 22 | 1 / 21 | 1 / 22 | 0 / 23 |
Outcome results
Primary
Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements
The primary effectiveness endpoint is a composite endpoint that considers radiographic and clinical measurements at six months post-implantation: the amount of linear bone growth (LBG), which is assessed with the use of radiographs, and the regain from baseline of clinical attachment level (∆CAL), which is assessed clinically. Linear bone growth (LBG) in a vertical and horizontal direction is determined radiographically at six months post-implantation. The clinical attachment level (CAL) is the distance from the cemento-enamel junction (CEJ) (or other fixed reference point) generally along the long axis of the tooth to the deepest extent of the periodontal pocket. The success criteria are ΔCAL ≥1.5 mm and LBG ≥1 mm at 6 months after the treatment. Both the ∆CAL and LBG must meet the success criteria for a subject to be considered a success.
Time frame: 6 months post-surgery
Population: The modified Intent-to-Treat population consisted of 83 subjects after two subjects were removed for lack of compliance with the study protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Beta-tricalcium Phosphate Alone | Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements | 16 Participants |
| GFeBGS 0.1% | Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements | 15 Participants |
| GFeBGS 0.3% | Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements | 19 Participants |
| GFeGBS 0.4% | Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements | 17 Participants |
Secondary
Change in Clinical Attachment Level at 3 Months
The clinical attachment level is the distance from the cemento-enamel junction (or other fixed reference point) generally along the long axis of the tooth to the deepest extent of the periodontal pocket. Change = (3 months measurement - Baseline measurement)
Time frame: Baseline and 3 months post-surgery
Population: The modified Intent-to-Treat population consisted of 84 subjects after a subject was removed for lack of compliance with the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beta-tricalcium Phosphate Alone | Change in Clinical Attachment Level at 3 Months | 3.1 mm | Standard Deviation 1.4 |
| GFeBGS 0.1% | Change in Clinical Attachment Level at 3 Months | 2.9 mm | Standard Deviation 1.7 |
| GFeBGS 0.3% | Change in Clinical Attachment Level at 3 Months | 3.1 mm | Standard Deviation 1.6 |
| GFeGBS 0.4% | Change in Clinical Attachment Level at 3 Months | 3.5 mm | Standard Deviation 1.7 |
Secondary
Change in Clinical Attachment Level at 6 Months
The clinical attachment level is the distance from the cemento-enamel junction (or other fixed reference point) generally along the long axis of the tooth to the deepest extent of the periodontal pocket. Change = (6 months measurement - Baseline measurement)
Time frame: Baseline and 6 months post-surgery
Population: The modified Intent-to-Treat population consisted of 83 subjects after two subjects were removed for lack of compliance with the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beta-tricalcium Phosphate Alone | Change in Clinical Attachment Level at 6 Months | 2.9 mm | Standard Deviation 2.1 |
| GFeBGS 0.1% | Change in Clinical Attachment Level at 6 Months | 2.5 mm | Standard Deviation 2.1 |
| GFeBGS 0.3% | Change in Clinical Attachment Level at 6 Months | 3.0 mm | Standard Deviation 1.4 |
| GFeGBS 0.4% | Change in Clinical Attachment Level at 6 Months | 3.6 mm | Standard Deviation 1.8 |
Secondary
Change in Gingival Recession at 3 Months
Length from the free gingival margin to the CEJ is measured in millimeter with North Carolina 15 mm periodontal probes. Gingival Recession = (3 months measurement - Baseline measurement)
Time frame: Baseline and 3 months post-surgery
Population: The modified Intent-to-Treat population consisted of 84 subjects after a subject was removed for lack of compliance with the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beta-tricalcium Phosphate Alone | Change in Gingival Recession at 3 Months | -0.6 mm | Standard Deviation 1.4 |
| GFeBGS 0.1% | Change in Gingival Recession at 3 Months | -0.6 mm | Standard Deviation 1.1 |
| GFeBGS 0.3% | Change in Gingival Recession at 3 Months | -0.3 mm | Standard Deviation 1.2 |
| GFeGBS 0.4% | Change in Gingival Recession at 3 Months | -0.3 mm | Standard Deviation 1.2 |
Secondary
Change in Gingival Recession at 6 Months
Length from the free gingival margin to the CEJ is measured in millimeter with North Carolina 15 mm periodontal probes. Gingival Recession = (6 months measurement - Baseline measurement)
Time frame: Baseline and 6 months post-surgery
Population: The modified Intent-to-Treat population consisted of 83 subjects after two subjects were removed for lack of compliance with the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beta-tricalcium Phosphate Alone | Change in Gingival Recession at 6 Months | -0.7 mm | Standard Deviation 1.5 |
| GFeBGS 0.1% | Change in Gingival Recession at 6 Months | -0.4 mm | Standard Deviation 1 |
| GFeBGS 0.3% | Change in Gingival Recession at 6 Months | -0.4 mm | Standard Deviation 1.1 |
| GFeGBS 0.4% | Change in Gingival Recession at 6 Months | -0.1 mm | Standard Deviation 1.3 |
Secondary
Linear Bone Growth at 6 Months
Linear measurement of bone height in millimeters along mesial and/or distal root surfaces of the defect site is captured radiographically at baseline and 6 months. Linear Bone Growth = (Baseline measurement - 6 months measurement)
Time frame: Baseline and 6 months post-surgery
Population: The modified Intent-to-Treat population consisted of 83 subjects after two subjects were removed for lack of compliance with the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beta-tricalcium Phosphate Alone | Linear Bone Growth at 6 Months | 3.1 mm | Standard Deviation 1.8 |
| GFeBGS 0.1% | Linear Bone Growth at 6 Months | 3.0 mm | Standard Deviation 1.2 |
| GFeBGS 0.3% | Linear Bone Growth at 6 Months | 3.7 mm | Standard Deviation 1.3 |
| GFeGBS 0.4% | Linear Bone Growth at 6 Months | 3.6 mm | Standard Deviation 2.1 |
Secondary
Percent Bone Fill at 6 Months
Linear measurement of bone height in millimeters along mesial and/or distal root surfaces of the defect site is captured radiographically at baseline and 6 months. Percent Bone Fill is calculated by dividing Linear Bone Growth at 6 months by bone height at baseline.
Time frame: Baseline and 6 months post-surgery
Population: The modified Intent-to-Treat population consisted of 83 subjects after two subjects were removed for lack of compliance with the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beta-tricalcium Phosphate Alone | Percent Bone Fill at 6 Months | 62.5 percentage of bone height change | Standard Deviation 26.4 |
| GFeBGS 0.1% | Percent Bone Fill at 6 Months | 61.0 percentage of bone height change | Standard Deviation 23 |
| GFeBGS 0.3% | Percent Bone Fill at 6 Months | 74.6 percentage of bone height change | Standard Deviation 20 |
| GFeGBS 0.4% | Percent Bone Fill at 6 Months | 71.1 percentage of bone height change | Standard Deviation 37.8 |
Secondary
Pocket Depth Change at 3 Months
Length from free gingival margin to the base of the pocket in millimeter is measured with North Carolina 15 mm periodontal probes. Pocket Depth Change = (3 months measurement - Baseline measurement)
Time frame: Baseline and 3 months post-surgery
Population: The modified Intent-to-Treat population consisted of 84 subjects after a subject was removed for lack of compliance with the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beta-tricalcium Phosphate Alone | Pocket Depth Change at 3 Months | 3.7 mm | Standard Deviation 1.4 |
| GFeBGS 0.1% | Pocket Depth Change at 3 Months | 3.5 mm | Standard Deviation 1.4 |
| GFeBGS 0.3% | Pocket Depth Change at 3 Months | 3.5 mm | Standard Deviation 1.6 |
| GFeGBS 0.4% | Pocket Depth Change at 3 Months | 3.8 mm | Standard Deviation 1.1 |
Secondary
Pocket Depth Change at 6 Months
Length from free gingival margin to the base of the pocket in millimeter is measured with North Carolina 15 mm periodontal probes. Pocket Depth Change = (6 months measurement - Baseline measurement)
Time frame: Baseline and 6 months post-surgery
Population: The modified Intent-to-Treat population consisted of 83 subjects after two subjects were removed for lack of compliance with the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beta-tricalcium Phosphate Alone | Pocket Depth Change at 6 Months | 3.7 mm | Standard Deviation 1.2 |
| GFeBGS 0.1% | Pocket Depth Change at 6 Months | 2.9 mm | Standard Deviation 2 |
| GFeBGS 0.3% | Pocket Depth Change at 6 Months | 3.4 mm | Standard Deviation 1 |
| GFeGBS 0.4% | Pocket Depth Change at 6 Months | 3.7 mm | Standard Deviation 1 |
Post Hoc
Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements (Updated Success Criteria)
The primary effectiveness endpoint is a composite endpoint that considers radiographic and clinical measurements at six months post-implantation: the amount of linear bone growth (LBG), which is assessed with the use of radiographs, and the regain from baseline of clinical attachment level (∆CAL), which is assessed clinically. Linear bone growth (LBG) in a vertical and horizontal direction is determined radiographically at six months post-implantation. The clinical attachment level (CAL) is the distance from the cemento-enamel junction (CEJ) (or other fixed reference point) generally along the long axis of the tooth to the deepest extent of the periodontal pocket. The updated success criteria are ΔCAL ≥1.5 mm and LBG ≥ 2.5 mm at 6 months after the treatment. Both the ∆CAL and LBG must meet the success criteria for a subject to be considered a success.
Time frame: 6 months post-surgery
Population: The modified Intent-to-Treat population consisted of 83 subjects after two subjects were removed for lack of compliance with the study protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Beta-tricalcium Phosphate Alone | Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements (Updated Success Criteria) | 9 Participants |
| GFeBGS 0.1% | Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements (Updated Success Criteria) | 10 Participants |
| GFeBGS 0.3% | Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements (Updated Success Criteria) | 15 Participants |
| GFeGBS 0.4% | Number of Participants That Met the Success Criteria of Radiographic and Clinical Measurements (Updated Success Criteria) | 15 Participants |