Study to Evaluate Efficacy of LAI When Added to Multi-drug Regimen Compared to Multi-drug Regimen Alone (CONVERT)
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|ClinicalTrials.gov Identifier: NCT02344004|
Recruitment Status : Active, not recruiting
First Posted : January 22, 2015
Results First Posted : November 20, 2018
Last Update Posted : February 12, 2019
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 subjects with Nontuberculous Mycobacterial (NTM) lung infection caused by Mycobacterium Avium Complex (MAC) that were refractory to treatment.
Subjects were randomized 2:1 to LAI 590 mg administered QD + MDR or MDR alone.
|Condition or disease||Intervention/treatment||Phase|
|Mycobacterium Infections, Nontuberculous||Drug: LAI (Liposomal Amikacin for Inhalation) 590 mg||Phase 3|
This is an ongoing randomized, open-label, multicenter study of LAI in adult subjects with NTM lung infections caused by MAC that were refractory to treatment. Subjects 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. Subjects 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, subjects were assessed as converters or non-converters.
A converter was defined as a subject 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 subject who did not have 3 consecutive monthly MAC-negative sputum cultures at any time within the first 6 months of the study.
All converters remained in the study. Converters who, after culture conversion, subsequently had MAC-positive sputum cultures in liquid broth media (agar negative) for 1 or 2 consecutive months only by Month 6 also remained in the study. Subjects who remained in the study continued their randomized treatment regimen until they completed a total of 12 months of treatment (EOT), starting from the first of 3 negative cultures that defined culture conversion. These subjects returned after the EOT visit for 28 days, 3, 6, and 12 months off-treatment follow-up visits. The 12 months off-treatment follow-up visit was the EOS visit. No NTM treatment was administered during the off-treatment phase.
At Month 8, all non-converters as assessed at the Month 6 visit were discontinued from Study INS-212. Subjects who experienced a relapse or recurrence by Month 6 also discontinued from Study INS-212 at their Month 8 visit. These subjects were potentially eligible to enter a separate open-label study of LAI (Study INS-312), provided all entry criteria were met for that study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||336 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||May 27, 2015|
|Actual Primary Completion Date :||July 7, 2017|
|Estimated Study Completion Date :||April 9, 2019|
No Intervention: Multi-drug Regimen
Subjects received their already prescribed anti-mycobacterial regimen (based on the 2007 ATS/IDSA Guidelines)
Experimental: LAI + Multi-drug Regimen
Subjects received LAI 590 mg QD in addition to their already prescribed anti-mycobacterial regimen (based on the 2007 ATS/IDSA Guidelines)
LAI (Liposomal Amikacin for Inhalation) 590 mg QD, administered by inhaling drug product that had been aerosolized in an eFlow nebulizer over approximately 14 minutes.
Drug: LAI (Liposomal Amikacin for Inhalation) 590 mg
LAI 590 mg QD, administered by inhaling drug product that had been aerosolized in an eFlow nebulizer over approximately 14 minutes.
- The Proportion of Subjects Achieving Culture Conversion (3 Consecutive Monthly Negative Sputum Cultures) by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm [ Time Frame: by 6 months ]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. Subjects 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 subject 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 subject in the ITT population (ie, all randomized subjects) was classified as either a converter or non-converter by Month 6.
- 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 [ Time Frame: 6 months and up to 16 months ]
A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and at Months 4, 6, and 8, for this initial analysis and again at the EOT visit, and at the 3 months off treatment visit for the latter analysis. The standardized protocol based on the ATS guidelines was used.
The 6MWT was conducted by a site member who was blinded to the subject's open-label treatment assignment.
The analysis of the change from Baseline (Day 1) to Month 6 in the 6MWT distance was performed after the last subject completed Month 6 and his/her 6MWT distance data were available.
- Time to Culture Conversion by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm [ Time Frame: by 6 months ]The time to culture conversion was defined by the date of the first of at least 3 consecutive monthly culture specimens that were MAC-negative.
- Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score [ Time Frame: by 6 months ]
The SGRQ was completed before administration of study drug at Baseline (Day 1) and Months 3, 6, 8, and 12, and at the EOT visit and the 3 months off-treatment visit. The SGRQ is a self-administered questionnaire that has been validated in subjects with airways disease, specifically in subjects with bronchiectasis. The SGRQ assesses health-related quality of life in subjects with chronic pulmonary disease by evaluating 3 health domains: symptoms (distress caused by respiratory symptoms); activity (effects of disturbances on mobility and physical activity); and impacts (the effect of disease on factors such as employment, personal control of one's health, and need for medication).
A composite total score is derived as the sum of domain scores for symptoms, activity, and impact (0=the best possible score and 100=the worst possible score). A reduction in score of 4 units is generally recognized as a clinically meaningful improvement in quality of life.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02344004
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|Study Director:||Gina Eagle, MD||Insmed Incorporated|