A Randomized, Open-label, Multicenter Study of Liposomal Amikacin for Inhalation (LAI) in Adult Patients With Nontuberculous Mycobacterial (NTM) Lung Infection Caused by Mycobacterium Avium Complex (MAC) That Are Refractory to Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 336
- 主要终点
- Number of Participants Achieving Durable Culture Conversion Through 3 Months Off Treatment in the LAI + MDR Arm Compared to the MDR Arm Alone
研究概览
简要总结
A study to evaluate the effectiveness of Liposomal Amikacin for Inhalation (LAI) 590 mg administered once daily (QD) when added to multi-drug regimen (MDR) in participants with Nontuberculous Mycobacterial (NTM) lung infection caused by Mycobacterium Avium Complex (MAC) that were refractory to treatment.
Participants were randomized 2:1 to LAI 590 mg administered QD + MDR or MDR alone.
详细描述
This is a randomized, open-label, multicenter study of LAI in adult participants with NTM lung infections caused by MAC that were refractory to treatment. Participants received either LAI 590 mg administered QD by inhalation plus a multidrug regimen, hereafter referred to as LAI + MDR or a multidrug regimen alone, hereafter referred to as MDR alone for a minimum of 8 months. Participants who demonstrated culture conversion by Month 6 went on to complete a treatment course of 12 months, starting from the first of 3 negative cultures that defined culture conversion.
Sputum culture results were made available to the site after the Month 6 sputum result was known, in time for the Month 8 visit. Prior to the Month 8 visit, the culture results from Baseline to Month 6 inclusively were blinded to the site and Sponsor. The results were blinded to reduce the potential for bias in an open-label study. At Month 8 (-28 to +7 days), after all sputum culture results were made available to the site only, up to and including Month 6, participants were assessed as converters or non-converters.
A converter was defined as a participant who had 3 consecutive monthly MAC-negative sputum cultures at any time within the first 6 months of the study.
"Relapse or recurrence" was defined as having MAC-positive sputum cultures in liquid broth media (agar negative) for 3 or more consecutive months, or having at least 1 MAC-positive sputum culture on solid media (agar positive) after achieving culture conversion.
A non-converter was defined as a participant who did not have 3 consecutive monthly MAC-negative sputum cultures at any time within the first 6 months of the study.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be continually positive for MAC on sputum culture while adhering to a multi-drug treatment regimen for a minimum duration of 6 months which is either ongoing or was completed no more than 12 months before screening
- •Be diagnosed with MAC NTM lung infection with evidence of nodular bronchiectasis and/or fibrocavitary disease by chest CT
- •Be willing to adhere to multi-drug treatment regimen during the course of the study
排除标准
- •Patients with cystic fibrosis
- •Positive pregnancy test or lactation at screening. All women of child bearing potential will be tested. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrheic for at least 1 year), or surgically or naturally sterile.
- •Active pulmonary tuberculosis requiring treatment at screening
- •History of lung transplantation
- •Prior exposure to LAI (including clinical study).
研究组 & 干预措施
LAI + Multi-drug Regimen
Participants received LAI 590 mg QD in addition to their already prescribed anti-mycobacterial regimen (based on the 2007 ATS/IDSA Guidelines)
LAI 590 mg QD, administered by inhaling drug product that had been aerosolized in an eFlow nebulizer over approximately 14 minutes
干预措施: LAI (Liposomal Amikacin for Inhalation) 590 mg (Drug)
结局指标
主要结局
Number of Participants Achieving Durable Culture Conversion Through 3 Months Off Treatment in the LAI + MDR Arm Compared to the MDR Arm Alone
时间窗: up to Month 19
Sputum specimens were collected at screening, baseline (Day 1), during treatment, and at Months 1, 3, 6, and 12 months off treatment. Culture conversion with durability was defined as achieving culture conversion by Month 6 and then having no more than 2 consecutive broth positive cultures and no Agar positive culture up to 3 months off treatment. Converters with missing broth or Agar sputum culture result after Month 6 up to 3 months off treatment were considered as not achieving culture conversion with durability except those participants who are unable to produce sputum despite reasonable efforts, as reported by source documentation. Participants who had relapse/recurrence, had "rescue" medication and/or died before reaching 3 months off treatment were considered as not achieving culture conversion with durability.
Number of Participants Achieving Culture Conversion by Month 6 in the Liposomal Amikacin for Inhalation (LAI) + Multi-drug Regimen (MDR) Arm Compared to the MDR Alone Arm
时间窗: by Month 6
Sputum specimens were collected at Screening (Visit 1), Baseline (Visit 2), and at Visits 3 (Month 1) through 8 (Month 6). A negative culture result reflected a negative culture result for all sputum samples collected at each visit. Participants met the primary endpoint of culture conversion by Month 6 if they had 3 consecutive monthly MAC-negative sputum cultures during the first 6 months of the study. A participant needed to achieve the first of 3 consecutive negative sputum cultures (that defined culture conversion) by Month 4 in order to meet the primary endpoint by Month 6. Each participant in the intent to treat (ITT) population (ie, all randomized participants) was classified as either a converter or non-converter by Month 6.
次要结局
- Change in 6-Minute Walk Test (6MWT) Distance at EOT in the LAI Arm Compared to a Multi-drug Regimen Alone(up to Month 16)
- Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm(at Month 6)
- Number of Participants Achieving Sustained Culture Conversion at the End of Treatment (EOT) in the LAI + MDR Arm Compared to the MDR Arm Alone(up to Month 16)
- Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score(at Month 6)
- Time to Culture Conversion by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm(by Month 6)