The first and only product studied in a Phase 3 trial for the treatment of refractory MAC lung disease1

Down arrow icon

ARIKAYCE is the only FDA-approved product studied in a Phase 3 trial for the treatment of refractory MAC lung disease1,3

CONVERT clinical trial1,3*

Scroll to see full chart. →
The CONVERT trial is an open-label study that enrolled 336 adult patients with refractory MAC lung disease. Following screening, patients were randomized 2:1 to either: once-daily ARIKAYCE (amikacin liposome inhalation suspension) + background regimen (n=224 patients) or background regimen alone (n=112 patients). The treatment phase of the trial was designed to run from baseline to Month 16. Patients in both arms were treated for a minimum duration of 8 months. The primary study endpoint was the percentage of patients who achieved culture conversion at Month 6. Select secondary endpoints included the 6MWT and SGRQ. A 12-month off-treatment phase was designed to run from Month 16 to Month 28 of the study. The confirmatory endpoint of this phase was sustained culture conversion at 3 months off treatment. Confirmatory endpoint results have not yet been established.
Footnotes

*The CONVERT trial is referred to as "Trial 1" in the ARIKAYCE full Prescribing Information.

Refractory MAC lung disease was defined as continued positive sputum cultures after a minimum duration of 6 consecutive months of background regimen therapy.1

A converter was defined as a patient who had 3 consecutive monthly MAC-negative sputum cultures at any time within the first 6 months of the study. All converters without relapse or recurrence remained in the study for 12 months, starting from the first negative culture that defines culture conversion. “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.3

§The 6MWT was conducted by using the standard protocol based on the ATS guidelines. After assessments were performed for heart rate, blood pressure, pulse oximetry, dyspnea, and overall fatigue using the Borg scale, patients were instructed to walk on a prescribed course as far as they could in 6 minutes. The maximum distance achieved was compared to the pretest values.3

||The change from baseline (Day 1) to Month 6 in SGRQ total score was analyzed.3

The confirmatory endpoint (sustained sputum culture conversion at 3 months after cessation of therapy) has not yet been established and will be evaluated along with all other study endpoints at the conclusion of the trial.3

Patients were considered to have refractory MAC lung disease if they did not achieve negative sputum cultures after a minimum duration of 6 consecutive months of background regimen therapy that was either ongoing or stopped no more than 12 months before the screening visit.1

Checkmark icon

Key inclusion criteria4

  • Had MAC lung disease documented by at least 2 positive cultures (at least 1 positive culture obtained within 6 months prior to screening and 1 positive culture at screening with cultures obtained at least 1 month apart)
  • Did not respond to active therapy for ≥6 months. Treatment was either ongoing or had been stopped no more than 12 months before the screening visit
  • Had evidence of MAC lung disease with underlying lung disease, such as nodular bronchiectasis and/or fibrocavitary disease by chest radiography or chest CT
X-mark icon

Key exclusion criteria4

  • Had cystic fibrosis
  • Had MAC lung disease that was resistant to amikacin (as identified by minimum inhibitory concentration susceptibility >64 μg/mL)
  • Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within 1 year before screening or anticipated during the study period
  • Had acquired and primary immunodeficiency syndromes (eg, HIV-positive patients regardless of CD4 counts)

The primary endpoint was culture conversion by Month 61,2

3 petri dishes with checkmarks icon

Culture conversion was defined as 3 consecutive monthly negative sputum cultures. The study design required 2 or 3 negative sputum samples per month for 3 consecutive months to confirm culture conversion.1,2

Warning mark icon
Sputum samples were collected in the absence of ARIKAYCE administration

Expectorated sputum (approximately 3 mL spontaneous or induced with nebulized hypertonic saline solution as needed) was collected at designated study visits in the CONVERT trial.3,4

The Phase 3 CONVERT trial protocol stipulated that patients were to refrain from administering ARIKAYCE on days that sputum samples were obtained, starting 2 days before the scheduled visit. This procedure minimized sample contamination with ARIKAYCE.3,4

Monthly schedule of sputum collection in CONVERT3,4

The monthly schedule of sputum collection in CONVERT trial stipulated the cycle that patients received ARIKAYCE (amikacin liposome inhalation suspension) for the first 28 days upon treatment initiation (Day 1-28/Month 1); ARIKAYCE was not administered and sputum was collected at home (Day 29-30/Month 1); sputum collected at study visit and ARIKAYCE administered after sputum collection (Day 1/Month 2); and patients started receiving ARIKAYCE again (Day 2-28/Month 2) continuing.

To improve the probability of obtaining a good sputum specimen, at least 2 (and preferably 3) sputum samples were obtained from each patient at each assessment. If a patient was unable to produce sputum spontaneously, one induced sputum specimen collected at the site was acceptable.4

In order to meet the primary endpoint at Month 6 of the study, patients would need to achieve their first negative sputum culture by Month 4.2

The additional endpoints of the change from baseline in 6MWT distance and the SGRQ were evaluated.1

The background regimen in CONVERT was aligned with current guidelines3

The background regimen was composed of an antimycobacterial regimen of at least 2 antibiotics based on the 2007 ATS/IDSA Statement or respective local guidelines. Patients in the CONVERT trial continued with the same background regimen for the duration of the study.3

At baseline, the background regimen included a macrolide (91.9%), a rifamycin (85.7%), or ethambutol (80.3%). Overall, 54.9% of patients were receiving a triple background regimen of a macrolide, a rifamycin, and ethambutol. An additional 11.3% of patients were on an existing background regimen of a macrolide, a rifamycin, ethambutol, plus a fourth antibiotic. Patients in the CONVERT trial continued with the same background regimen for the duration of the study.1,3,4

Summary of background regimen in the CONVERT trial at baseline4

Scroll to see full chart. →
In the ARIKAYCE (amikacin liposome inhalation suspension) + background regimen arm (n=223) vs the background regimen alone arm (112), respectively: the background regimen consisted of 0 drugs (0.9% vs 2.7%), 2 drugs (17.5% vs 12.5%), 3 drugs (66.4% vs 75.0%), or 4+ drugs (15.2% vs 9.8%). 82.5% vs 75.9% of background regimens contained ethambutol; 92.8% vs 90.2% contained a macrolide, 85.7% vs 83.9% contained rifamycin; and 30.9% vs 34.8% contained other drug classes. 13.5% vs 7.1% of drug combinations included ethambutol, macrolide, rifamycin, and other drug classes; 55.2% vs 54.5% included ethambutol, macrolide, and rifamycin; 2.7% vs 5.4% included ethambutol, macrolide, and other drug classes; 5.8% vs 2.7% included ethambutol and macrolide; 3.6% vs 5.4% included ethambutol, rifamycin, and other drug classes; 5.8% vs 10.7% included macrolide, rifamycin, and other drug classes; 5.8% vs 4.5% included macrolide and rifamycin; and 4.0% vs 5.4% included macrolide and other drug classes.
Footnote

#Other may include medications such as fluoroquinolones, linezolid, clofazimine, or agents deemed to be a component of the background regimen by the investigator, excluding parenteral amikacin and/or streptomycin as defined in the protocol.4

More about the CONVERT clinical trial

The efficacy and safety of ARIKAYCE were evaluated in an ongoing, open-label, randomized (2:1), multicenter, global, Phase 3 trial of 336 adult patients with refractory MAC lung disease as confirmed by at least 2 sputum culture results.1-3

Which patients in your practice could benefit from ARIKAYCE?

See patient types
Right arrow icon
Trial design icon
Understanding the open-label trial design

In the CONVERT clinical trial, a 2-arm, open-label, non–placebo-controlled study design was selected to provide a more complete evaluation of the ARIKAYCE safety profile. Comparing ARIKAYCE to a placebo, like the liposomal vehicle (empty liposomes without amikacin), in a blinded study would not have provided a clear assessment of safety, as the nebulization of a placebo may have made it difficult to distinguish the adverse effects associated with liposome inhalation from amikacin inhalation.2,3

Baseline characteristics2,3

Scroll to see full chart. →
In the ARIKAYCE (amikacin liposome inhalation suspension) + background regimen arm (n=224), background regimen alone arm (n=112), and total trial population (N=336), respectively: median duration of MAC lung disease was 4.45, 3.26, and 3.96 years (medians for the ARIKAYCE + background regimen arm and total trial population were based on the safety population); 89.7%, 90.2%, and 89.9% of patients were on treatment prior to enrollment; 10.3%, 9.8%, and 10.1% were off treatment for at least 3 months; 11.6%, 8.9%, and 10.7% of patients were current smokers (including e-cigarette use); 88.4%, 91.1%, and 89.3% were not current smokers; COPD was the underlying lung disease of 12.9%, 17.0%, and 14.3% of patients; bronchiectasis was the underlying lung disease of 65.2%, 57.1%, and 62.5% of patients; comorbid COPD and bronchiectasis were the underlying lung diseases of 9.8%, 16.1%, and 11.9% of patients; and 10.7%, 13.4%, and 11.6% of patients had received prior nebulized IV amikacin.
Footnotes

**Based on safety population (n=223).3

††Based on safety population (N=335).3

‡‡COPD was derived from the medical history data.3

Demographic characteristics2,3

Scroll to see full chart. →
In the ARIKAYCE (amikacin liposome inhalation suspension) + background regimen arm (n=224), background regimen alone arm (n=112), and total trial population (N=336), respectively: mean age was 64.6, 64.9, and 64.7 years; standard deviation was 9.59, 10.16, and 9.77 years; 41.5%, 42.9%, and 42.0% of enrolled patients were from the USA; 6.3%, 5.4%, and 6.0% were from Asia, excluding Japan; 15.2%, 12.5%, and 14.3% were from Japan; 37.1%, 39.3%, and 37.8% were from the rest of the world; 26.3%, 39.3%, and 30.7% of enrolled patients were male; and 73.7%, 60.7%, and 69.3% were female.
Patient population icon

The CONVERT trial evaluated patients who were refractory to treatment. Patients were considered to have refractory MAC lung disease if they did not achieve negative sputum cultures after a minimum duration of 6 consecutive months of background regimen therapy. Treatment was either ongoing or had been stopped no more than 12 months before the screening visit.1

6MWT=6-minute walk test; ATS=American Thoracic Society; CT=computed tomography; HIV=human immunodeficiency virus; IDSA=Infectious Diseases Society of America; IV=intravenous; MAC=Mycobacterium avium complex; SD=standard deviation; SGRQ=St George's Respiratory Questionnaire.

References

  1. ARIKAYCE [package insert]. Bridgewater, NJ: Insmed Incorporated; 2018.
  2. Griffith DE, Eagle G, Thomson R, et al. Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT): a prospective, open-label, randomized study. Am J Respir Crit Care Med. 2018;198(12):1559-1569.
  3. Data on file. Insmed Incorporated. Bridgewater, NJ.
  4. Griffith DE, Eagle G, Thomson R, et al. Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex. Online data supplement. Am J Respir Crit Care Med. 2018;198(12)(suppl):E1-E28. https://www.atsjournals.org/doi/suppl/10.1164/rccm.201807-1318OC. Accessed January 2, 2019.