A Phase 2, Randomized, Double-blind, Parallel, Placebo-controlled Study to Evaluate Efficacy and Safety of Local Injection of Human Dental Pulp Mesenchymal Stem Cells for the Treatment of Chronic Periodontitis Patients.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 204
- 试验地点
- 1
- 主要终点
- Changes from baseline in height of the periodontal bone defect
研究概览
简要总结
The primary objective:To evaluate the efficacy of different administration protocols of human dental pulp mesenchymal stem cells for the treatment of chronic periodontitis patients.
The secondary objective:To evaluate the safety of different administration protocols of human dental pulp mesenchymal stem cells for the treatment of chronic periodontitis patients.
The exploratory objective:To investigate the effects of human dental pulp mesenchymal stem cells on biomarkers in gingival crevicular fluid in chronic periodontitis patients.
详细描述
This is a multicenter, randomized, double-blind, parallel, placebo-controlled study, including three treatment groups which are single-dose group, two-dose group (low-dose), and two-dose group (high-dose). The patients of single-dose group will receive only one dose on day 1 (D1), and the patients of two-dose groups will receive one dose on D1 and D90 respectively. 68 participants will be enrolled in each group, and be randomized (3:1) to receive human dental pulp mesenchymal stem cells (hDP-MSCs) or placebo (normal saline). Participants in the single-dose group and the two-dose group (high-dose) will receive local injection of 1.0 × 107 hDP-MSCs (0.6mL normal saline suspension) / periodontal defect site or 0.6mL normal saline / periodontal defect site, and participants in the two-dose group (low-dose) will receive local injection of 1.0 × 106 hDP-MSCs (0.6mL normal saline suspension) / periodontal defect site or 0.6mL normal saline / periodontal defect site. All participants will receive basic periodontal treatment simultaneously.
Dosing interval: the dosing interval is set at 89 days, which is based on the results of preclinical trials of hDP-MSCs, the improvement of periodontitis observed on D90 after hDP-MSCs administration, and good safety profile in phase 1 clinical trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •18 to 65 years old (including threshold), unlimited gender; 2)Radiological examination of the periodontal defect site shows angular bone defect; 3)The probing depth (PD) at the periodontal defect site is 4 to 8 mm at baseline; 4)Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures; 5)Voluntarily participate in the clinical study, understand and sign the informed consent;
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Participants with severe periodontal diseases (alveolar bone resorption exceeds two-thirds of the tooth root length) which affect the investigator's judgment;
- •The grade of studied tooth looseness ≥ grade 3 at baseline (only buccolingual movement is defined as grade 1; buccolingual and mesiodistal movement is grade 2; vertical loosening is grade 3);
- •The studied tooth with occlusal trauma which affect the investigator's judgment;
- •Participants with surgical treatment of previous periodontal defect sites and adjacent periodontal tissues;
- •Participants with non-steroid anti-inflammatory drug, steroid hormone therapy, and/or other hormone (except topical hormones) treatment within past 3 months of the screening visit, and/or previous use of bisphosphonates;
- •Participants with severe systemic infection within past 3 months of the screening visit, or antibiotics treatment within past 72h of the screening visit;
- •Participants with uncontrolled hypertension within 1 month before screening (defined as sitting systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg after receiving the optimal antihypertensive therapy);
- •Participants with severe or uncontrolled diseases in any system (cardiac, hepatic, renal, respiratory, hematologic, endocrine, nervous, or psychiatric);
- •Participants are known to be allergic to any materials that may be used during surgery (allergy-prone constitution or history of allergy to blood products);
- •Any of the following abnormalities in clinical laboratory tests at screening: ALT > 3 ULN, total bilirubin > 1.5 ULN, serum creatinine > 1.5 ULN, international normalized ratio (INR) ≥ 1.5 ULN or activated partial thromboplastin time (APTT) ≥ 1.5 ULN (except for patients receiving anticoagulation therapy), Hb < 80 g/L, or PLT < 75.0×109/L;
- •Positive result for any of the following tests at screening: hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or Treponema pallidum antibody (TP-Ab);
- •Females who are pregnant or breastfeeding;
- •Participants and their partners who plan to conceive or do not agree to use the effective non-pharmacological method of contraceptive during the trial from screening visit to 6 months after the end of the trial;
- •Participants participated in other clinical studies within past 3 months of the screening visit;
- •Participants with a history of smoking addiction within past 12 months of the screening visit (the number of cigarettes smoked per day ≥ 10); Other circumstances deemed inappropriate by the investigator.
研究组 & 干预措施
single-dose group
Human Dental Fulp Stem Cells Injection: 1X 10^7 cells/periodontaldefect site.
干预措施: Human Dental Fulp Stem Cells (Drug)
two-dose group (low-dose)
Human Dental Pulp Stem Cells Injection: 1X 10^6 cells/periodontaldefect site. Continuous administration twice, with an interval of 89 days between each administration.
干预措施: Human Dental Fulp Stem Cells (Drug)
two-dose group (high-dose)
Human Dental Pulp Stem Cells Injection: 1X 10^7 cells/periodontaldefect site. Continuous administration twice, with an interval of 89 days between each administration.
干预措施: Human Dental Fulp Stem Cells (Drug)
结局指标
主要结局
Changes from baseline in height of the periodontal bone defect
时间窗: at baseline, 90 days, 180 days
Changes from baseline in height of the periodontal bone defect which will be examined by CBCT at D90±7 and D180±14 (primary efficacy endpoint)
次要结局
- Changes from baseline in respiration rate of Vital Signs(within 180 days after administration)
- Changes from baseline in heart rate of Vital Signs(within 180 days after administration)
- Changes from baseline in blood pressure of Vital Signs(within 180 days after administration)
- Changes from baseline in body temperature of Vital Signs(within 180 days after administration)
- Changes from baseline in red blood cell count of Laboratory Examination(within 180 days after administration)
- Changes from baseline in lymphocyte count of Laboratory Examination(within 180 days after administration)
- Changes from baseline in platelet count of Laboratory Examination(within 180 days after administration)
- Changes from baseline in total bilirubin of Laboratory Examination(within 180 days after administration)
- Changes from baseline in white blood cell count of Laboratory Examination(within 180 days after administration)
- Changes from baseline in neutrophil count of Laboratory Examination(within 180 days after administration)
- Changes from baseline in total bile acid of Laboratory Examination(within 180 days after administration)
- Changes from baseline in urea of Laboratory Examination(within 180 days after administration)
- Changes from baseline in creatinine of Laboratory Examination(within 180 days after administration)
- Changes from baseline in uric acid of Laboratory Examination(within 180 days after administration)
- Changes from baseline in glucose of Laboratory Examination(within 180 days after administration)
- Changes from baseline in potassium of Laboratory Examination(within 180 days after administration)
- Changes from baseline in sodium of Laboratory Examination(within 180 days after administration)
- Changes from baseline in chlorine of Laboratory Examination(within 180 days after administration)
- Changes from baseline in Pregnancy test of Laboratory Examination(within 180 days after administration)
- Changes from baseline in urine specific gravity of Laboratory Examination(within 180 days after administration)
- Changes from baseline in urine pH of Laboratory Examination(within 180 days after administration)
- Changes from baseline in hemoglobin of Laboratory Examination(within 180 days after administration)
- Changes from baseline in INR of Laboratory Examination(within 180 days after administration)
- Changes from baseline in direct bilirubin of Laboratory Examination(within 180 days after administration)
- Changes from baseline in ALT of Laboratory Examination(within 180 days after administration)
- Changes from baseline in AST of Laboratory Examination(within 180 days after administration)
- Changes from baseline in total protein of Laboratory Examination(within 180 days after administration)
- Changes from baseline in albumin of Laboratory Examination(within 180 days after administration)
- Changes from baseline in APTT of Laboratory Examination(within 180 days after administration)
- Changes from baseline in PT of Laboratory Examination(within 180 days after administration)
- Changes from baseline in Detection of infectious diseases of Laboratory Examination(within 180 days after administration)
- Changes from baseline in IgA of Laboratory Examination(within 180 days after administration)
- Changes from baseline in IgG of Laboratory Examination(within 180 days after administration)
- Changes from baseline in IgM of Laboratory Examination(within 180 days after administration)
- Changes from baseline in total IgE of Laboratory Examination(within 180 days after administration)
- Changes from baseline in urine glucose of Laboratory Examination(within 180 days after administration)
- Changes from baseline in urine protein of Laboratory Examination(within 180 days after administration)
- Changes from baseline in urine ketone body of Laboratory Examination(within 180 days after administration)
- Changes from baseline in urine occult blood of Laboratory Examination(within 180 days after administration)
- Changes from baseline in ECG PR interval(within 180 days after administration)
- Changes from baseline in ECG QRS interval(within 180 days after administration)
- Changes from baseline in ECG RR interval(within 180 days after administration)
- Changes from baseline in ECG QT interval(within 180 days after administration)
- Incidence of Treatment-Emergent Adverse Event(within 180 days after administration)
- Change from baseline in Clinical Attachment Level (AL)(at baseline, 90 days, 180 days)
- Change from baseline in Tooth Mobility (TM)(at baseline, 90 days, 180 days)
- Change from baseline in Probing Depth (PD)(at baseline, 90 days, 180 days)
- Change from baseline in Gingival recession （GR）(at baseline, 90 days, 180 days)
- Change from baseline in Probing bleeding on probing (BOP)(at baseline, 90 days, 180 days)
- Changes from baseline in urine white blood cell of Laboratory Examination(within 180 days after administration)
- Changes from baseline in urine bilirubin of Laboratory Examination(within 180 days after administration)