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，以完成正在进行的1/2期临床试验，以评估 脂氧素类似物BLXA 4-ME口服冲洗液治疗以下疾病的安全性和初步疗效 牙龈炎。本研究包括3组，随机、安慰剂对照、双盲临床试验， 试验设计，治疗组，安慰剂冲洗组和无冲洗对照组。的 治疗组（1.0 μM BLXA 4-ME口腔含漱液）和安慰剂含漱液组包括50名受试者。 无冲洗对照组由25名受试者组成。接受治疗和安慰剂冲洗的受试者 组在早晨刷牙后接受口腔冲洗（BLXA 4-ME或安慰剂），每天使用一次 刷牙将在治疗前和第3、7、14、21和28天评估安全性参数 经过初步治疗。将在治疗前以及第14天和第28天评估疗效参数 经过初步治疗。主要目的是评价研究药物的安全性。 化合物BLXA 4-ME，作为每日口腔冲洗液局部应用于牙龈炎症成人。 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。将监测受试者的 将分析牙周炎和口腔植物群的发展或进展， 机会生物次要目的是评估口服 通过监测菌斑指数（PI）、改良牙龈指数（MGI）、 龈沟液（GCF）中白细胞介素-1 β（IL-1β）水平， 治疗前后血清中特异性脂质介质谱的变化。活性 制备液（供试漱口液）将在含有10% 乙醇和0.25%十二烷基硫酸钠。化合物BLXA 4-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 BLXA 4-ME，在四烯的2个位置之间引入稠合的O-取代的苯并环 天然脂氧素A4单位。安慰剂制剂将由配制的口腔冲洗液组成， BLXA4ME。每例受试者参与研究的持续时间约为3个月（访视至 最后一次产品使用后28天加2个月的安全性随访电话）。招聘率为 每月约20名受试者，其中6-8名被随机化。根据这一比例， 预计招募将在12个月内完成。