Periodontal Disease
Conditions
Brief summary
The purpose of this study is to determine whether ST266 will reduce pocket depth (PD) as an adjunctive to scaling and root planing (SRP) in subjects with moderate to severe periodontal disease.
Detailed description
The study is a 9-month, randomized, double-blind, parallel-design study of subjects with existing moderate to severe periodontal disease randomly assigned to one of three groups. The primary endpoint of PD change will be evaluated following 9 months of treatment. Subjects will be followed for 9 months for safety and radiographic evaluations. Subjects who meet inclusion criteria will be randomized to one of three treatment groups. Randomization will be stratified by site and smoker status (never smoked or quit smoking more than two years ago vs. has smoked within the last two years). Randomization will be blocked such that assignment to treatment groups both within sites and within smoker status will be approximately even (1:1:1). Treatment will be initiated after SRP. All subjects will be evaluated at baseline and Days 1, 15, 30, 60, 90, 180, and 270.
Interventions
BIOLOGICALST266
1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).
DRUGSaline (0.9% NaCl)
Saline applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. Saline will be applied directly to the marginal gingiva around each tooth (buccal and lingual).
Sponsors
Noveome Biotherapeutics, formerly Stemnion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed, written informed consent prior to participation in any study-related procedures. * Good general health as evidenced by medical history. * Between 18 and 85 years of age at time of informed consent signature. * Male or female. * Minimum of 18 teeth, excluding third molars. * Having moderate to severe periodontal disease according to AAP definition (at least 6 teeth ≥6 mm PD and ≥3 mm CAL at baseline). * Having \>30 percent bleeding sites upon probing. * Willing to abstain from chewing gums and other mouth rinses for the study duration. * Ability and willingness to attend all study visits and comply with all study visits and comply with all study procedures and requirements. * Willingness to abstain from routine dental care. * For women with reproductive potential, willingness to use highly effective contraception (e.g. licensed hormonal contraception, intrauterine device, abstinence, or vasectomy in partner).
Exclusion criteria
* Presence of orthodontic appliances. * A soft or hard tissue tumor of the oral cavity. * Any dental condition that requires immediate treatment, such as carious lesions. * Participation in any other clinical study within 30 days of screening or during the study. * Pregnancy or lactation. If a subject meets this criterion, she may be rescreened for study participation when she no longer meets this criterion. * Antibiotic therapy within the last 30 days. * Chronic use (≥3 times/week) of anti-inflammatory medications (e.g., non-steroidal anti inflammatory drugs, steroids). Low-dose aspirin (less than 325 mg daily) is allowed. * Immunocompromised subjects. * Subjects with cancer or a history of cancer within the last 5 years of screening. * Any medical history or any concomitant medication that might affect the assessment of the study treatment or periodontal tissues, such as diabetes, nifedipine, phenytoin (Dilantin), or anticoagulant medications (e.g., warfarin \[Coumadin\] etc.). * Involvement in the planning or conduct of the study. * History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or interfere with interpretation of the subject's study results. * Previous randomization for treatment in the present study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Baseline; 9 months | The primary efficacy endpoint of this study is the change from baseline in the PD at 9 months (Day 270) for those pockets ≥6 mm at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Clinical Attachment Level (CAL) | Baseline, 9 months | Change in Clinical Attachment Level (CAL) (the measurement of the position of the soft tissue in relation to the cemento-enamel junction (CEJ) that is a fixed point, using probing depth and the distance from the gingival margin to the CEJ.) from baseline in CAL at 9 months (Day 270) in tooth sites with baseline PD ≥ 6mm. |
| Bleeding on Probing (BOP) | Baseline and 9 months | A secondary efficacy endpoint of this study is change from baseline in BOP at 9 months (Day 270) with BOP for each subject calculated as the percentage of tooth sites in the whole mouth with BOP. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Group 1 received ST266 treatment daily on Days 1 through 5, 8 through 12, 22, and 30, and then monthly for 7 months (Days 60, 90, 120, 150, 180, 210, and 240).
ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual). | 52 |
| Group 2 Group 2 received ST266 treatment 2x/week (with at least 1 day between treatments) for the first 3 months, and then monthly for 5 months (Days 120, 150, 180, 210, and 240).
ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual). | 49 |
| Group 3 Group 3 received commercially available sterile saline (0.9% sodium chloride) according to the same schedule as Group 1.
Saline (0.9% NaCl): Saline applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. Saline will be applied directly to the marginal gingiva around each tooth (buccal and lingual). | 50 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 49.4 years STANDARD_DEVIATION 12.52 | 51.6 years STANDARD_DEVIATION 11.91 | 52.5 years STANDARD_DEVIATION 11.16 | 51.1 years STANDARD_DEVIATION 11.88 |
| Age, Customized 55 - ≤ 65 years | 13 Participants | 12 Participants | 16 Participants | 41 Participants |
| Age, Customized ≤ 55 years | 34 Participants | 29 Participants | 28 Participants | 91 Participants |
| Age, Customized > 65 years | 5 Participants | 8 Participants | 6 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 13 Participants | 9 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 36 Participants | 40 Participants | 115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 14 Participants | 15 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 10 Participants | 7 Participants | 30 Participants |
| Race (NIH/OMB) White | 25 Participants | 23 Participants | 22 Participants | 70 Participants |
| Sex: Female, Male Female | 22 Participants | 21 Participants | 25 Participants | 68 Participants |
| Sex: Female, Male Male | 30 Participants | 28 Participants | 25 Participants | 83 Participants |
| Smoking Status Non-Smoker | 39 Participants | 35 Participants | 37 Participants | 111 Participants |
| Smoking Status Smoker | 13 Participants | 14 Participants | 13 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 49 | 0 / 50 |
| other Total, other adverse events | 29 / 52 | 27 / 49 | 24 / 50 |
| serious Total, serious adverse events | 2 / 52 | 2 / 49 | 2 / 50 |
Outcome results
Primary
Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline
The primary efficacy endpoint of this study is the change from baseline in the PD at 9 months (Day 270) for those pockets ≥6 mm at baseline.
Time frame: Baseline; 9 months
Population: Intention-to-Treat (ITT) population: All randomized subjects with non-missing data for a given endpoint and time point. If the proportion of subjects (and oral sites) with missing data is ≤5 percent, as we expect it to be, for these analyses we will use the non-missing data and ignore the missingness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Pocket Depth (mm) - Change from Baseline | -2.1 Pocket Depth (mm) | Standard Deviation 1.4 |
| Group 1 | Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Pocket Depth (mm) - Day 270 | 4.5 Pocket Depth (mm) | Standard Deviation 1.45 |
| Group 1 | Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Pocket Depth (mm) - Baseline | 6.6 Pocket Depth (mm) | Standard Deviation 0.93 |
| Group 2 | Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Pocket Depth (mm) - Change from Baseline | -2.0 Pocket Depth (mm) | Standard Deviation 1.39 |
| Group 2 | Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Pocket Depth (mm) - Baseline | 6.6 Pocket Depth (mm) | Standard Deviation 1.02 |
| Group 2 | Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Pocket Depth (mm) - Day 270 | 4.6 Pocket Depth (mm) | Standard Deviation 1.53 |
| Group 3 | Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Pocket Depth (mm) - Day 270 | 4.5 Pocket Depth (mm) | Standard Deviation 1.49 |
| Group 3 | Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Pocket Depth (mm) - Baseline | 6.7 Pocket Depth (mm) | Standard Deviation 1.03 |
| Group 3 | Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline | Pocket Depth (mm) - Change from Baseline | -2.1 Pocket Depth (mm) | Standard Deviation 1.44 |
p-value: 0.341Generalized Estimating Equation
p-value: 0.774Generalized Estimating Equations
Secondary
Bleeding on Probing (BOP)
A secondary efficacy endpoint of this study is change from baseline in BOP at 9 months (Day 270) with BOP for each subject calculated as the percentage of tooth sites in the whole mouth with BOP.
Time frame: Baseline and 9 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | Bleeding on Probing (BOP) | Bleeding on Probing (%) - Day 270 | 40.9 Percentage of bleeding tooth-sites | Standard Deviation 20.8 |
| Group 1 | Bleeding on Probing (BOP) | Bleeding on Probing (%) - Baseline | 67 Percentage of bleeding tooth-sites | Standard Deviation 17.51 |
| Group 1 | Bleeding on Probing (BOP) | Bleeding on Probing (%) - Change from Baseline | -26.2 Percentage of bleeding tooth-sites | Standard Deviation 18.52 |
| Group 2 | Bleeding on Probing (BOP) | Bleeding on Probing (%) - Day 270 | 38.8 Percentage of bleeding tooth-sites | Standard Deviation 19.96 |
| Group 2 | Bleeding on Probing (BOP) | Bleeding on Probing (%) - Baseline | 62.8 Percentage of bleeding tooth-sites | Standard Deviation 15.84 |
| Group 2 | Bleeding on Probing (BOP) | Bleeding on Probing (%) - Change from Baseline | -24.0 Percentage of bleeding tooth-sites | Standard Deviation 21.23 |
| Group 3 | Bleeding on Probing (BOP) | Bleeding on Probing (%) - Baseline | 67.5 Percentage of bleeding tooth-sites | Standard Deviation 19.15 |
| Group 3 | Bleeding on Probing (BOP) | Bleeding on Probing (%) - Change from Baseline | -25.8 Percentage of bleeding tooth-sites | Standard Deviation 19.42 |
| Group 3 | Bleeding on Probing (BOP) | Bleeding on Probing (%) - Day 270 | 41.7 Percentage of bleeding tooth-sites | Standard Deviation 25.2 |
p-value: 0.816ANCOVA
p-value: 0.706ANCOVA
Secondary
Changes in Clinical Attachment Level (CAL)
Change in Clinical Attachment Level (CAL) (the measurement of the position of the soft tissue in relation to the cemento-enamel junction (CEJ) that is a fixed point, using probing depth and the distance from the gingival margin to the CEJ.) from baseline in CAL at 9 months (Day 270) in tooth sites with baseline PD ≥ 6mm.
Time frame: Baseline, 9 months
Population: Intention-to-Treat (ITT) population: All randomized subjects with non-missing data for a given endpoint and time point. If the proportion of subjects (and oral sites) with missing data is ≤5 percent, as we expect it to be, for these analyses we will use the non-missing data and ignore the missingness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | Changes in Clinical Attachment Level (CAL) | Clinical Attachment Level (mm) - Day 270 | 5.1 Clinical Attachment Level (mm) | Standard Deviation 2.01 |
| Group 1 | Changes in Clinical Attachment Level (CAL) | Clinical Attachment Level (mm) - Baseline | 6.7 Clinical Attachment Level (mm) | Standard Deviation 1.69 |
| Group 1 | Changes in Clinical Attachment Level (CAL) | Clinical Attachment Level (mm) - Difference from Baseline | -1.6 Clinical Attachment Level (mm) | Standard Deviation 1.48 |
| Group 2 | Changes in Clinical Attachment Level (CAL) | Clinical Attachment Level (mm) - Day 270 | 5.1 Clinical Attachment Level (mm) | Standard Deviation 1.92 |
| Group 2 | Changes in Clinical Attachment Level (CAL) | Clinical Attachment Level (mm) - Baseline | 6.8 Clinical Attachment Level (mm) | Standard Deviation 1.62 |
| Group 2 | Changes in Clinical Attachment Level (CAL) | Clinical Attachment Level (mm) - Difference from Baseline | -1.7 Clinical Attachment Level (mm) | Standard Deviation 1.79 |
| Group 3 | Changes in Clinical Attachment Level (CAL) | Clinical Attachment Level (mm) - Baseline | 6.7 Clinical Attachment Level (mm) | Standard Deviation 1.7 |
| Group 3 | Changes in Clinical Attachment Level (CAL) | Clinical Attachment Level (mm) - Difference from Baseline | -1.6 Clinical Attachment Level (mm) | Standard Deviation 1.6 |
| Group 3 | Changes in Clinical Attachment Level (CAL) | Clinical Attachment Level (mm) - Day 270 | 5.1 Clinical Attachment Level (mm) | Standard Deviation 2.05 |
p-value: 0.501Generalized Estimating Equations
p-value: 0.486Generalized Estimating Equations