Mycobacterium Infections, Nontuberculous Clinical Trial
Official title:
A Randomized, Double-Blind, Placebo-Controlled Study of Liposomal Amikacin for Inhalation in Patients With Recalcitrant Nontuberculous Mycobacterial Lung Disease
Verified date | August 2019 |
Source | Insmed Incorporated |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is to evaluate the efficacy, safety and tolerability of 84 days of
daily dosing of 590 mg of LAI versus placebo in patients with treatment refractory NTM lung
disease.
The first part of the study is the 84-day double-blind phase to evaluate the primary and
secondary endpoints.
Status | Completed |
Enrollment | 90 |
Est. completion date | June 18, 2015 |
Est. primary completion date | August 18, 2014 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 85 Years |
Eligibility |
Key Inclusion Criteria: 1. Diagnosis of pulmonary nontuberculous mycobacterial lung disease in accordance with the 2007 ATS/IDSA criteria with evidence of nodular bronchiectasis and/or cavitary disease by chest computed tomography (CT). 2. History of chronic infection with either Mycobacterium avium complex or Mycobacterium abscessus or mixed infection with both species (defined as at least 2 documented positive cultures in the prior 2 years, of which at least one was obtained in the 6 months prior to screening). 3. Positive sputum culture obtained at screening visit with either Mycobacterium avium complex or Mycobacterium abscessus or mixed infection with one dominant species. 4. Receiving ATS/IDSA guidelines-based treatment regimen defined as: adherent to a multi-drug regimen for at least 6 months prior to screening with persistently positive mycobacterial cultures. 5. Ability to produce at least 3 mL of sputum or be willing to undergo an induction that produces at least 3 mL of sputum for clinical evaluation. 6. Female of childbearing potential agrees to practice an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD). Key Exclusion Criteria: 1. Forced Expiratory Volume in 1 second (FEV1) <30% of predicted at Screening. 2. Presence of any clinically significant cardiac disease as determined by Investigator. The QTc criteria for Exclusion is QTc> 450 msec for males or QTc> 470 msec for females. 3. Subjects with hemoptysis of =60 mL in a 24 hour period within 4 weeks prior to screening. 4. Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within one year prior to screening or anticipated during the study period. 5. Active allergic bronchopulmonary mycosis or any other condition requiring systemic steroids at a dose > equivalent of 10 mg/day of prednisone within 3 months prior to screening or anticipated during the study period. 6. Pulmonary tuberculosis requiring treatment or treated within 2 years prior to screening. 7. History of lung transplantation. 8. Hypersensitivity to aminoglycosides. 9. Any change in chronic NTM multi-drug regimen within 28 days prior to Study Day 1. 10. Evidence of biliary cirrhosis with portal hypertension. 11. History of daily, continuous oxygen supplementation. 12. Smoking tobacco or any substance within 6 months prior to screening or anticipated inability to refrain from smoking throughout the study. Subjects with CF or primary ciliary dyskinesia were eligible to participate in the study if all eligibility criteria defined above were met. Subjects with CF were required to have documented confirmation of CF to be eligible for the study. The CF diagnosis had to be documented by a positive sweat test = 60 mmol/L or by DNA analysis revealing both mutated alleles consistent with CF disease. |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Insmed Incorporated | National Institute of Allergy and Infectious Diseases (NIAID) |
United States, Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. | The endpoint used the 7-step semi-quantitative scale (SQS) for mycobacterial culture reporting in both solid and liquid growth media, with step 1 = culture negative in both solid and liquid media, step 2 = growth in liquid medium only, 3 = solid medium positive, 4 = 50 to 100 colonies in solid medium & growth in liquid, 5 = >100 to 200 colonies in solid medium & growth in liquid, 6 = >200 to 500 colonies in solid medium & growth in liquid, 7 = >500 colonies in solid medium & growth in liquid. Full scale range is 1 (best score) to 7 (worst score). The change in step measures the growth at Day 84 compared to the growth at Baseline. The negative values represent reduction in colony growth. | Baseline and end of double-blind phase of 84 days | |
Secondary | Number of Subjects With Negative NTM Culture for the LAI Arm at Day 84 Compared to the Placebo Arm at Day 84 | Sputum specimens were cultured in liquid media in addition to solid media (agar). If results were negative on agar, the liquid media was held for 6 weeks before reporting as culture negative. Culture was negative when confirmed with no growth in liquid medium. | 84 days double-blind phase | |
Secondary | Time to Negative NTM Culture….During the 84-day Double-blind Treatment Phase | Sputum specimens were cultured in liquid media in addition to solid media (agar). If results were negative on agar, the liquid media was held for 6 weeks before reporting as culture negative. Culture was negative when confirmed with no growth in liquid medium. | 84 days double-blind phase | |
Secondary | Ordinal, 3-level Response From Baseline on the SQS for Mycobacterial Culture for the LAI Arm at Day 84 Compared to the Placebo Arm at Day 84 | The ordinal, 3-level response are (1) improvement (2) no change (3) worsening or death | Baseline and end of double-blind phase of 84 days | |
Secondary | Change From Baseline in Respiratory and Systemic Symptoms Questionnaire (RSSQ) Score at Day 84 for the LAI Arm Compared to the Placebo Arm | The RSSQ was administered to gather information from the subject about the types of symptoms that the subject has experienced since the last contact. A reduction in score indicates improvement. The range of values for the scores are -2 (best) to +2 (worst) in whole numbers. The composite score was calculated by averaging the scores of the subscales. | Baseline to day 84. | |
Secondary | Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm | The assessing physician asked the subject to rate his/her assessment of health according to the GRH. Subject responses to, "How would you rate your health at the present time?" included: Excellent, Good, Fair, or Poor. | Baseline and end of double-blind phase of 84 days | |
Secondary | Number of Participants Requiring "Rescue" Anti-mycobacterial or Other "Rescue" Drugs During the 84-day Double-blind Phase | Per the study protocol, study subjects were on a stable, multi-drug, anti-mycobacterial regimen based on the 2007 ATS/IDSA Guidelines; the regimen should not have changed during the study period except for safety concerns. The need for changes to the concurrent anti-mycobacterial regimen or "rescue" therapy was at the discretion of the Investigator and was tracked as a study outcome. | 84 days double-blind phase | |
Secondary | Number of Subject for "Rescue" Anti-mycobacterial or Other "Rescue" Drugs During the 84-day Double-blind Phase | Per the study protocol, study subjects were on a stable, multi-drug, anti-mycobacterial regimen based on the 2007 ATS/IDSA Guidelines; the regimen should not have changed during the study period except for safety concerns. The need for changes to the concurrent anti-mycobacterial regimen or "rescue" therapy was at the discretion of the Investigator and was tracked as a study outcome. | 84 days double-blind phase |
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