Phase 1/2 Clinical Trial to assess the safety and preliminary efficacy of Lipoxin Analog BLXA4-MEOral Rinse for the Treatment of Gingivitis

评估脂氧素类似物 BLXA4-MEOral 冲洗液治疗牙龈炎的安全性和初步疗效的 1/2 期临床试验

• 批准号: 9322800
• 负责人: HATICE HASTURK
• 金额: $ 87.03万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9322800
• 关键词: Acute; Adult; Adverse event; Aftercare; Agonist; Anabolism; Anti-Inflammatory Agents; Anti-inflammatory; Arachidonic Acids; Arthritis; Aspirin; Attenuated; Autacoids; Award; CD59 Antigen; Cardiovascular Diseases; Cell Adhesion Molecules; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Complex; Control Groups; Cyclooxygenase Inhibitors; Development; Dinoprostone; Disease; Double-Blind Method; Eicosanoids; Enrollment; Essential Fatty Acids; Ethanol; Event; Flowers; Formulation; Funding; Gingiva; Gingival Crevicular Fluid; Gingival Indexes; Gingivitis; Goals; Gram-Negative Bacteria; Healed; Hemorrhage; Immune response; In Situ; Incidence; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Interleukin-1 beta; Laboratories; Lesion; Leukotrienes; Lipoxins; Lipoxygenase; Maintenance; Mediating; Mediator of activation protein; Modality; Molecular; Monitor; Mucositis; Non-Steroidal Anti-Inflammatory Agents; Oral; Oral health; Organ; Organism; Pathogenesis; Pathway interactions; Periodontal Diseases; Periodontitis; Periodontium; Phagocytes; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Play; Porphyromonas gingivalis; Positioning Attribute; Preparation; Process; Production; Prostaglandins; Protocols documentation; Public Health; Randomized; Reactive Oxygen Species; Regulation; Resolution; Role; Safety; Series; Serum; Signal Transduction; Sodium Dodecyl Sulfate; TNF gene; Telephone; Testing; Therapeutic; Thromboxanes; Tissues; Tooth Loss; Tooth structure; Toothbrushing; Topical application; Transforming Growth Factors; Visit; analog; arachidonate; base; bone; chemical reaction; cyclooxygenase 2; cytokine; follow-up; gallin; healing; indexing; inhibitor/antagonist; injured; lipid mediator; lipoxin A4; microbial; neutrophil; oral bacteria; parent grant; programs; receptor; response; soft tissue; trafficking; treatment group

Project Summary This application seeks funding to complete an ongoing Phase 1/2 Clinical Trial to assess the safety and preliminary efficacy of Lipoxin Analog BLXA4-ME Oral Rinse for the Treatment of Gingivitis. The study comprises 3 groups in a randomized, placebo-controlled, double-blind clinical trial design, a treatment group, the placebo rinse group and the no-rinse control group. The treatment group (1.0 μM BLXA4-ME oral rinse) and the placebo rinse group include 50 subjects. The no-rinse control group consists of 25 subjects. Subjects in the treatment and placebo rinse groups receive oral rinse (BLXA4-ME or placebo) to be used once daily after morning teeth brushing. Safety parameters will be assessed before treatment and 3, 7, 14, 21, and 28 days after initial treatment. Efficacy parameters will be assessed before treatment and 14 and 28 days after initial treatment. The primary objective is to evaluate the safety of an investigational compound, BLXA4-ME, topically applied as a daily oral rinse in adults with gingival inflammation. Safety assessments will include the incidence of adverse events, including mucosal inflammation and irritancy, and findings from safety laboratory tests. Subjects will be monitored for development or progression of periodontitis and oral flora will be analyzed to detect an increase in opportunistic organisms. The secondary objective is to assess preliminary efficacy of the oral rinse, by monitoring changes in the plaque index (PI), modified gingival index (MGI), bleeding on probing (BOP) sensitivity, levels of interleukin-1β (IL-1β) in gingival crevicular fluid (GCF) and changes in the specialized lipid mediator profile in serum before and after treatment. The active preparation (test rinse) will contain BLXA4-ME at 1.0 μM in a formulated oral rinse containing 10% ethanol and 0.25% sodium lauryl sulfate. The compound BLXA4-ME is an analog of lipoxin A4, a locally acting lipid mediator biosynthesized from the essential fatty acid, arachidonic acid. In BLXA4-ME, a fused o-substituted benzo-ring is incorporated between 2 positions of the tetraene unit of native lipoxin A4. The placebo preparation will consist of formulated oral rinse without BLXA4ME. The duration of participation of each subject is approximately 3 months (visits through 28 days plus safety follow-up phone call 2 months after last product use). The recruitment rate is approximately 20 subjects per month of which 6-8 are randomized. Based upon this rate, it is estimated that enrollment will be completed in 12 months.

项目摘要 该申请寻求资金来完成正在进行的1/2临床试验进行评估 Lipoxin Analog Blxa4-Me口服冲洗的安全性和初步效率用于治疗 牙龈炎。该研究包括3组，以随机，安慰剂对照，双盲临床 试验设计，一个治疗组，安慰剂冲洗组和无里边对照组。这 治疗组（1.0μmBlxa4-Me口服冲洗），安慰剂冲洗组包括50名受试者。 无里根对照组由25名受试者组成。治疗和安慰剂冲洗的受试者 小组接受口服冲洗（BLXA4-ME或安慰剂），每天在晨牙后使用一次 刷牙。安全参数将在治疗前和3、7、14、21和28天进行评估 初始治疗后。疗效参数将在治疗前和14天和28天进行评估 初始治疗后。主要目的是评估研究的安全性 化合物Blxa4-Me，在牙龈炎症的成年人中局部用作每日口腔冲洗。 安全评估将包括不良事件的事件，包括粘膜注射 和刺激性，以及安全实验室测试的发现。受试者将受到监视 将分析牙周炎和口腔菌群的发展或进展，以检测 机会主义生物。次要目标是评估口服的初步效率 冲洗，通过监视斑块指数（PI）的变化，修饰的牙龈指数（MGI），出血 探测（BOP）敏感性，牙龈裂纹液（GCF）中白介素-1β（IL-1β）的水平和 治疗前后血清中专门的脂质介质轮廓的变化。活动 制备（测试冲洗）将在包含10％的配制口腔冲洗中以1.0μm的blxa4-me包含Blxa4-Me 乙醇和0.25％Lauryl硫酸钠。复合Blxa4-Me是脂氧蛋白A4的类似物 局部作用的脂质介体生物合成，从必需的脂肪酸，花生四烯酸。在 blxa4-me，一种融合的O取代的Benzo-Ring，在四个位置之间合并 天然脂蛋白A4的单位。安慰剂的准备将包括配制的口头冲洗 blxa4me。每个受试者的参与时间约为3个月（访问 28天加上安全后续电话，在上次产品使用后2个月）。招聘率是 每月约有20名受试者，其中6-8被随机分组​​。基于此速率，是 估计入学率将在12个月内完成。