A Phase IIa, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of 3% LTX-109 Compared to Placebo for Nasal Decolonisation of Staphylococcus Aureus.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Operating Window Eradication
研究概览
简要总结
A Phase IIa, double-blind, placebo-controlled, randomised study designed to evaluate the efficacy, safety and tolerability of two dosing regimens with LTX-109 administered topically to the anterior nares in subjects with persistent carriage of Staphylococcus aureus (S. aureus).
详细描述
Approximately 90 subjects planned screened to achieve 27 randomised and dosed subjects with persistent S. aureus carriage.
On Day 1, subject randomisation in a 2:1 ratio to receive either LTX-109 (n=18) or placebo (n=9). Cohort (1 [8 doses] or 2 [6 doses]) used as a stratification variable to preserve the 2:1 treatment randomisation ratio in each cohort (LTX-109 n=9 or placebo n=5/4).
For all subjects, the IMP was to be applied 4 times during an intensive dosing regimen for 4 ½-hours (on Day 1 at 0, 1 ½, 3 and 4 ½ - hours). For subjects in Cohort 1, this was followed by 4 additional applications: on Day 1 at 12 hours, on Day 2 at 24 and 36 hours, and on Day 3 at 48 hours. For subjects in Cohort 2 the IMP was likewise applied 4 times during the 4 ½-hour period (on Day 1 at 0, 1 ½, 3 and 4½ hours), but was followed by 2 applications: on Day 1 at 12 hours and on Day 2 at 36 hours. On each dosing occasion, a large drop (approximately 250 μL) of IMP was applied into each nostril and distributed to cover the whole area of the nostril. The subjects were carefully monitored by clinical staff during and after dosing. Safety assessments (AEs, vital signs, safety laboratory assessments and local tolerability) and efficacy assessments (nasal swab) were performed.
All subjects were instructed to wash the body and hair with chlorhexidine body wash and shampoo at the CRU on Day 1 (prior to the first dose) and on Day 2. Subjects were provided with chlorhexidine body wash and shampoo for body and hair wash at home on Day 3, Day 4, Day 5, Day 6 and Day 7. On Day 3 and Day 7, subjects used the chlorhexidine shower before the visits to the CRU.
A final end-of-study visit (Visit 5) took place on Day 7 (+2 days) or after early withdrawal.
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
- Triple (Participant, Care Provider, Investigator)
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
- 是
入选标准
- •Willing and able to give written informed consent for participation in the study.
- •Male or female subject aged 18 to 65 years, inclusive.
- •Persistent nasal carrier of S. aureus (MSSA), confirmed by 2 positive bacterial cultures from the nose during the screening period.
- •Medically healthy subjects without abnormal clinically significant medical history, physical findings, vital signs, or laboratory values at the time of screening, as judged by the Investigator.
- •Women of child bearing potential (WOCBP) had to practice abstinence (only allowed when this was the preferred and usual lifestyle of the subject) or had to agree to use a highly effective method of contraception with a failure rate of < 1% to prevent pregnancy from the date of dosing until 2 weeks after last dose. Female subjects had to refrain from donating eggs from the date of dosing until 3 months after dosing with the IMP. Their male partner had to agree to use a condom from date of first dosing until 2 weeks after last dose if he had not undergone vasectomy.
- •Male subjects had to be willing to use condom or had to be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner and had to refrain from donating sperm from the date of dosing until 3 months after dosing with the IMP. Their female partner of child-bearing potential had to use contraceptive methods with a failure rate of < 1% to prevent pregnancy (see above).
排除标准
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, could either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- •Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of IMP.
- •Severe eczema or skin wounds, dry or sensitive skin assessed as clinically significant by the Investigator.
- •Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody and HIV.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to LTX-109 or chlorhexidine.
- •S. aureus (MSSA and/or MRSA) decolonisation attempt in the 6 months prior to - MRSA positive at screening (Visit 1 and/or Visit 2).
- •Inability to take medications nasally.
- •Nasal polyps or significant anatomical nasal abnormality, as judged by the Investigator.
- •Evidence of open wound, lesion, inflammation, erythema or infection (including active rhinitis, sinusitis or upper respiratory infection or severe acne vulgaris) affecting the nostril area, lip and skin close to the nose.
- •History of multiple episodes (>3) of epistaxis within 12 months prior to screening Visit
- •Disease in the region of the application sites, significant history of trauma or skin disease in the region of the application sites, current nasal skin or nasal septum condition requiring treatment or nasal surgery in the 6 months prior to screening Visit
- •In situ nasal jewellery or open nasal piercings.
- •Previous or concurrent treatment with antimicrobials for an infection within the last 28 days prior to the first administration of IMP.
研究组 & 干预措施
Placebo
Vehicle treatment
干预措施: Vehicle gel, 4 + 4 applications or 4 + 2 applications (Drug)
Cohort 1
For all subjects, the IMP was applied 4 times during an intensive dosing regimen for 4 ½-hours (on Day 1 at 0, 1 ½, 3 and 4 ½ - hours). For subjects in Cohort 1, this was followed by 4 additional applications: on Day 1 at 12 hours, on Day 2 at 24 and 36 hours, and on Day 3 at 48 hours.
干预措施: LTX-109 3% gel, 4 + 4 applications (Drug)
Cohort 2
For all subjects, the IMP was applied 4 times during an intensive dosing regimen for 4 ½-hours (on Day 1 at 0, 1 ½, 3 and 4 ½ - hours). For subjects in Cohort 2 the IMP was likewise applied 4 times during the 4 ½-hour period (on Day 1 at 0, 1 ½, 3 and 4½ hours), but was followed by 2 applications: on Day 1 at 12 hours and on Day 2 at 36 hours.
干预措施: LTX-109 3% gel, 4 + 2 applications (Drug)
结局指标
主要结局
Operating Window Eradication
时间窗: 6 hour to 12 hours after start of treatment
Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 6 hours, from 6 to 12 hours after start of treatment (the "Operation Window").
次要结局
- Percentage change in colony forming units (CFUs) in subjects from baseline(4.5 hours, 6 hours, 12 hours)
- Asessment of Vital Signs (Systolic and diastolic blood pressure and pulse)(24 hours, 54 hours and Day 7)
- Safety laboratory assessments(54 hours and Day 7)
- Adverse events(Through treatment and followup of 7 days)
- Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 48 hours(From 6 hours to 54 hours after start of treatment)
- Local tolerability assessed by health care professional(Pre-dose, 1.5 hours, 4.5 hours, 6 hours, 12, hrs, 54 hours and Day 7)
- Local tolerability assessed by the subject(Pre-dose, 1.5 hours, 4.5 hours, 6 hours, 12, hrs, 54 hours and Day 7)
- Number eradicated at specific timepoints(4.5 hours, 6 hours, 12 hours)