Periodontitis
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled Phase II clinical study designed to evaluate the clinical efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of multiple local injections of different doses of LP-005 injection in patients with moderate-to-severe periodontitis, and to investigate changes in biomarker levels.
Interventions
DRUGLP-005 Injection
LP-005 is a bifunctional antibody fusion protein consisting of an anti-human C5 monoclonal antibody and a human complement regulatory protein, formulated as a sterile injectable solution. Each vial contains 300 mg of LP-005 in 6 mL (50 mg/mL). The LP-005 is administered via interdental papilla injection.
DRUGPlacebo Injection
Placebo is a sterile injectable solution matched to LP-005 for appearance, formulation, and administration, with 0 mg of active ingredient per 6 mL vial.
Sponsors
Longbio Pharma (Suzhou) Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18 to 70 years (inclusive), with no restriction on sex. 2. Clinically diagnosed with moderate to severe (Stage II or III) periodontitis according to the 2018 International Classification of Periodontal and Peri-Implant Diseases. participants must have at least 2 non-adjacent natural teeth (excluding third molars) in the dentition with a Probing Depth (PD) of 5 to 8 mm (inclusive), and at least 1 site per tooth with a BI score \> 2. 3. Participants and their partners must agree to practice effective non-pharmacological contraception from the time of signing the Informed Consent Form (ICF) until 3 months after the study completion. For female participants of childbearing potential, a negative pregnancy test result is required within 7 days prior to the first dose. 4. Voluntary participation in the trial and signed approval of the ICF.
Exclusion criteria
1. At the time of screening, the target tooth and/or adjacent teeth (as determined by the investigator to affect the target tooth) exhibit periapical periodontitis, pericoronitis, or combined pulp-periodontal lesions; or the participant has orthodontic appliances (including fixed lingual retainers, etc.); 2. At screening, the target tooth and/or adjacent teeth (as determined by the investigator to affect the target tooth) are found by the investigator to have severe caries or caries requiring immediate treatment; 3. At screening, the participant has a periodontal or dental abscess, or a tumor of the oral soft or hard tissues; 4. Participants who have previously undergone periodontal surgery on the target teeth and/or adjacent teeth (as determined by the investigator to affect the target teeth), or who have undergone subgingival scaling and root planning (SRP) within 6 months prior to screening; 5. Participants with a history of Neisseria meningitidis infection; 6. Participants with a history of splenectomy or congenital asplenia; 7. Participants with impaired immune function (e.g., HIV infection, neutropenia, complement deficiency, etc.); 8. Participants with autoimmune diseases that the investigator determines may interfere with the evaluation of the study disease, such as Sjögren's syndrome, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, etc.; 9. Participants with poorly controlled blood pressure at screening, such as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg; 10. Participants with glycated hemoglobin (HbA1c) \>7.5% or severe diabetic complications at screening; 11. Participants with severe or poorly controlled systemic diseases at screening, as determined by the investigator, such as respiratory, gastrointestinal, cardiovascular, hematological, urological, neurological, or psychiatric disorders; 12. Participants who have continuously taken medications deemed by the investigator to interfere with the study within 1 month prior to screening, such as nifedipine, phenytoin, or anticoagulants (e.g., warfarin); 13. Participants who have received systemic antibiotic therapy within 3 months prior to screening; 14. Participants who have taken nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids on a long-term basis (≥3 times per week) prior to screening; 15. Participants with any of the following laboratory test results at the time of screening: * ALT or AST \> 2.5 times the upper limit of normal (ULN) or serum total bilirubin \> 1.5 times ULN; * Serum creatinine \> 1.5 times the upper ULN; * International Normalized Ratio (INR) ≥ 1.5 times ULN, or activated partial thromboplastin time (APTT) ≥ 1.5 times ULN (excluding participants currently receiving anticoagulant therapy); * Platelet count (PLT) \< 100 × 10⁹/L; 16. Participants who test positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or Treponema pallidum antibody (TP-Ab) at screening; 17. Participants with a history of malignant tumors within 5 years prior to screening; 18. Participants with a history of heavy smoking (≥10 cigarettes per day) within 12 months prior to screening; 19. Participants with known allergies to any drugs or materials used during surgery; 20. Pregnant or breastfeeding women; 21. Participants who have participated in other clinical trials within 30 days prior to screening or who plan to participate in other clinical trials during the study period; 22. Participants assessed by the investigator as having other conditions rendering them unsuitable for participation in the clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Gingival Index (GI) | Day 43, Day 85, Day 127, and Day 169 | GI is measured using the Löe-Silness scale (range: 0-3), where higher scores indicate more severe gingival inflammation (worse outcome). Changes from baseline in gingival index (GI) scores are measured at Day 43, Day 85, Day 127, and Day 169 after the first administration of LP-005 injection. |
| Change from Baseline in Bleeding Index (BI) | Day 43, Day 85, Day 127, and Day 169 | BI is measured using the Caton-Paton scale (range: 0-4), where higher scores indicate more severe gingival bleeding (worse outcome). Changes from baseline in BI scores are measured at Day 43, Day 85, Day 127, and Day 169 after the first administration of LP-005 injection. |
| Change from Baseline in Probing Pocket Depth (PD) | Day 43, Day 85, Day 127, and Day 169 | Changes from baseline in probing pocket depth (PD) are measured at Day 43, Day 85, Day 127, and Day 169 after the first administration of LP-005 injection. |
| Change from Baseline in Clinical Attachment Loss (AL) | Day 43, Day 85, and Day 127, Day 169 | Clinical AL is evaluated by standardized periodontal probing: after measuring probing depth, the probe tip is withdrawn along the root surface to identify the cemento-enamel junction (CEJ). The distance from the CEJ to the gingival margin (GM) is recorded. AL is calculated by subtracting this distance from the probing depth. A result of zero or an undetectable CEJ indicates no attachment loss. In cases of gingival recession where the gingival margin is apical to the CEJ, AL is determined by summing the two measurements. Six sites per tooth are examined, and AL values are recorded at all measured sites, with units expressed in millimeters (mm); larger values represent more severe periodontal attachment destruction. Changes from baseline in AL are measured at Day 43, Day 85, Day 127, and Day 169 after the first administration of LP-005 injection. |
| Change from Baseline in Plaque Index (PI) | Day 43, Day 85, Day 127, and Day 169 | PI is measured using the Silness-Löe scale (range: 0-3), higher scores indicate thicker dental plaque accumulation and more severe periodontal plaque condition. Changes from baseline in plaque index (PI) scores are measured at Day 43, Day 85, Day 127, and Day 169 after the first administration of LP-005 injection. |
| Change from Baseline in Alveolar Bone Defect Height | Day 85, and Day 169 | Changes from baseline in alveolar bone defect height are measured at Day 85 and Day 169 after the first administration of LP-005 injection, assessed via cone-beam computed tomography (CBCT). |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Up to approximately 24 weeks | Incidence and severity of TEAEs from first dose to end of study are recorded. |
| Detect Pharmacokinetic (PK) Characteristics of LP-005 | Up to approximately 24 weeks | Assess detectable serum concentration of LP-005 after local administration; if sufficient systemic exposure is detected, evaluate the systemic plasma PK characteristics of LP-005. |
| Gingival Crevicular Fluid (GCF) Concentration of LP-005 | Up to approximately 24 weeks | GCF samples to evaluate changes in LP-005 concentration in participants' GCF after local administration. |
| Detect Pharmacodynamics (PD) Characteristics of LP-005 | Up to approximately 24 weeks | Collect systemic venous blood samples to evaluate changes in participants' serum complement hemolytic activity (CH50), free C5 level, and C3b deposition after local administration of LP-005. |
| Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Assessment | Up to approximately 24 weeks | Collect systemic venous blood samples to evaluate the positivity rate of ADA in participants, the titer of ADA-positive samples, and further detect NAb in ADA-positive samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Gingival Crevicular Fluid (GCF) Biomarker Levels | Up to approximately 24 weeks | GCF samples will be collected in participants' GCF after local administration of LP-005 to assess changes from baseline in a predefined panel of inflammatory and tissue-degrading biomarkers, including C3b, C5a, IL-1β, IL-6, TNF-α, MMP-8, and MMP-9. All biomarkers are quantified in standardized protein concentration units within GCF, and individual biomarker changes will be reported separately without aggregation. |
Countries
China
Contacts
CONTACTJie Yang
PRINCIPAL_INVESTIGATORHong Hua
Peking University School and Hospital of Stomatology
Outcome results
None listed