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.

项目概要 该申请寻求资金来完成正在进行的 1/2 期临床试验以评估 脂氧素类似物 BLXA4-ME 口腔冲洗液治疗的安全性和初步疗效 牙龈炎。该研究包括 3 组随机、安慰剂对照、双盲临床研究 试验设计，治疗组，安慰剂冲洗组和不冲洗对照组。这 治疗组（1.0 μM BLXA4-ME 口腔冲洗剂）和安慰剂冲洗组包括 50 名受试者。 免冲洗对照组由 25 名受试者组成。接受治疗和安慰剂冲洗的受试者 各组接受漱口水（BLXA4-ME 或安慰剂），每天在晨牙后使用一次 刷牙。将在治疗前以及治疗后 3、7、14、21 和 28 天评估安全参数 初步治疗后。疗效参数将在治疗前以及治疗后 14 天和 28 天进行评估 初步治疗后。主要目标是评估研究的安全性 化合物 BLXA4-ME，作为每日口腔冲洗剂局部应用于患有牙龈炎症的成人。 安全性评估将包括不良事件的发生率，包括粘膜炎症 和刺激性，以及安全实验室测试的结果。受试者将受到监测 将分析牙周炎和口腔菌群的发生或进展，以检测牙周炎和口腔菌群的增加 机会有机体。第二个目标是评估口服药物的初步疗效 冲洗时，通过监测菌斑指数（PI）、改良牙龈指数（MGI）、出血情况的变化 探诊（BOP）敏感性、龈沟液（GCF）中白细胞介素-1β（IL-1β）水平和 治疗前后血清中特殊脂质介质谱的变化。活跃的 制剂（测试冲洗液）将在含有 10% 的配制口腔冲洗液中含有 1.0 μM 的 BLXA4-ME 乙醇和0.25%十二烷基硫酸钠。化合物 BLXA4-ME 是脂氧素 A4 的类似物， 由必需脂肪酸花生四烯酸生物合成的局部作用脂质介质。在 BLXA4-ME，稠合的邻位取代苯并环掺入四烯的 2 个位置之间 天然脂氧素A4的单位。安慰剂制剂将由配制的口腔冲洗液组成，不含 BLXA4ME。每个科目的参与持续时间约为3个月（通过访问 28 天，加上最后一次使用产品后 2 个月的安全跟进电话）。招聘率为 每月大约 20 名受试者，其中 6-8 名被随机分配。根据这个比率， 预计注册将在12个月内完成。