Efficacy and Safety of LP-005 Injection in Patients With Moderate-to-Severe Periodontitis

Official title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase Ⅱ Study to Evaluate the Efficacy and Safety of LP-005 Injection in Patients With Moderate-to-Severe Periodontitis

Overview

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

• Drug LP-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.
• Drug Placebo 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.

Primary outcome measures

• Change from Baseline in Gingival Index (GI) [Time frame: Day 43, Day 85, Day 127, and Day 169]
• Change from Baseline in Bleeding Index (BI) [Time frame: Day 43, Day 85, Day 127, and Day 169]
• Change from Baseline in Probing Pocket Depth (PD) [Time frame: Day 43, Day 85, Day 127, and Day 169]
• Change from Baseline in Clinical Attachment Loss (AL) [Time frame: Day 43, Day 85, and Day 127, Day 169]
• Change from Baseline in Plaque Index (PI) [Time frame: Day 43, Day 85, Day 127, and Day 169]
• Change from Baseline in Alveolar Bone Defect Height [Time frame: Day 85, and Day 169]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Up to approximately 24 weeks]
• Detect Pharmacokinetic (PK) Characteristics of LP-005 [Time frame: Up to approximately 24 weeks]
• Gingival Crevicular Fluid (GCF) Concentration of LP-005 [Time frame: Up to approximately 24 weeks]
• Detect Pharmacodynamics (PD) Characteristics of LP-005 [Time frame: Up to approximately 24 weeks]

Secondary outcome measures (1)

• Change from Baseline in Gingival Crevicular Fluid (GCF) Biomarker Levels [Time frame: Up to approximately 24 weeks]

Eligibility criteria

Inclusion criteria

• Aged 18 to 70 years (inclusive), with no restriction on sex.
• 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.
• 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.
• Voluntary participation in the trial and signed approval of the ICF.

Exclusion criteria

• 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.);
• 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;
• At screening, the participant has a periodontal or dental abscess, or a tumor of the oral soft or hard tissues;
• 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;
• Participants with a history of Neisseria meningitidis infection;
• Participants with a history of splenectomy or congenital asplenia;
• Participants with impaired immune function (e.g., HIV infection, neutropenia, complement deficiency, etc.);
• 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.;
• Participants with poorly controlled blood pressure at screening, such as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg;
• Participants with glycated hemoglobin (HbA1c) >7.5% or severe diabetic complications at screening;
• 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;
• 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);
• Participants who have received systemic antibiotic therapy within 3 months prior to screening;
• Participants who have taken nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids on a long-term basis (≥3 times per week) prior to screening;
• 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;
• 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;
• Participants with a history of malignant tumors within 5 years prior to screening;
• Participants with a history of heavy smoking (≥10 cigarettes per day) within 12 months prior to screening;
• Participants with known allergies to any drugs or materials used during surgery;
• Pregnant or breastfeeding women;
• 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;
• Participants assessed by the investigator as having other conditions rendering them unsuitable for participation in the clinical study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University School and Hospital of Stomatology — Beijing

Identifiers

NCT: NCT07603713 · P10-LP005-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗