ALIS for Nontuberculous Mycobacterial Infections

(ENCORE Trial)

Recruiting at 320 trial locations

Overseen By Fraz Ismat

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Insmed Incorporated

Must be taking: Azithromycin, Ethambutol

Must not be taking: Corticosteroids, Macrolides

Disqualifiers: Cystic fibrosis, COPD, HIV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 13 months

425 Participants Needed

Trial Summary

What is the purpose of this trial?

The main objective of this study is to evaluate the efficacy of ALIS (amikacin liposome inhalation suspension) + background regimen (azithromycin \[AZI\] + ethambutol \[ETH\]) compared to the ELC (empty liposome control) + background regimen on participant-reported respiratory symptoms at Month 13.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently receiving mycobacterial antibiotic treatment for a MAC lung infection, you may not be eligible to participate.

What evidence supports the effectiveness of the drug ALIS for treating nontuberculous mycobacterial infections?

Research shows that azithromycin, a component of ALIS, is effective in treating Mycobacterium avium complex (MAC) lung disease, with success rates of 55-65% in different regimens. Additionally, azithromycin and clarithromycin, another similar drug, have shown effectiveness against nontuberculous mycobacteria in animal studies, suggesting potential benefits for human treatment. ^{1 2 3 4 5}

Is ALIS safe for treating nontuberculous mycobacterial infections?

ALIS (Amikacin liposome inhalation suspension) has been approved for treating Mycobacterium avium complex infections and is designed to minimize side effects by targeting the lungs directly. Early-phase studies have shown it to be generally safe, but like any medication, it may have some adverse effects. ^{6 7 8 9 10}

How is the drug ALIS for Nontuberculous Mycobacterial Infections different from other treatments?

The drug ALIS, combined with azithromycin and ethambutol, is unique because it includes a macrolide antibiotic (azithromycin) that is effective against nontuberculous mycobacteria and is well-tolerated, potentially improving survival and quality of life for patients. This combination targets the bacteria more effectively than some traditional treatments, which may not be as active against these infections. ^{1 3 11 12 13}

Eligibility Criteria

This trial is for adults with a lung infection caused by Mycobacterium Avium Complex (MAC) who haven't started treatment, haven't had a lung transplant, don't have cystic fibrosis, and have never taken ALIS before. Participants must be at least 18 years old, or the age of majority in their country.

Inclusion Criteria

You have an ongoing MAC lung infection and have not yet started treatment.

You have not had a lung transplant.

You do not have a disease called cystic fibrosis.

Exclusion Criteria

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ALIS (amikacin liposome inhalation suspension) or ELC (empty liposome control) along with azithromycin and ethambutol daily

13 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ALIS
• Azithromycin
• ELC (matching placebo for ALIS)
• Ethambutol

Trial Overview The study tests if inhaling ALIS (amikacin liposome inhalation suspension) combined with azithromycin and ethambutol improves respiratory symptoms after 13 months compared to an empty liposome control plus the same background regimen.

Participant Groups

Group I: ALIS + Background Regimen Experimental Treatment 3 Interventions

Participants will be administered 590 mg of ALIS (amikacin liposome inhalation suspension) once daily. Participants will also be administered azithromycin 250 mg and ethambutol 15 mg/kg, once daily.

Group II: ELC + Background Regimen Placebo Group 3 Interventions

Participants will be administered ELC (empty liposome control), a visually matching placebo to ALIS (amikacin liposome inhalation suspension), once daily. Participants will also be administered azithromycin 250 mg and ETH (ethambutol) 15 mg/kg, once daily.

Who Is Running the Clinical Trial?

Insmed Incorporated

Lead Sponsor

Trials

44

Recruited

7,600+

Findings from Research

In a study involving 92 patients with pulmonary Mycobacterium avium complex (MAC) disease, multidrug regimens containing azithromycin were effective, with treatment success rates of 59% for daily dosing, 55% for thrice-weekly dosing with daily companions, and 65% for thrice-weekly dosing with thrice-weekly companions.

All treatment regimens, which included rifabutin or rifampin and ethambutol, showed no significant differences in outcomes, indicating that both daily and thrice-weekly azithromycin regimens are viable options for treating MAC lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin-containing regimens for treatment of Mycobacterium avium complex lung disease. Griffith, DE., Brown, BA., Girard, WM., et al.[2022]

In a study using inbred C57BL/6 mice and a macrophage model, the combination of rifabutin, clarithromycin, and ethambutol showed the best results against the Mycobacterium avium strain 101, indicating that combination therapy may enhance efficacy.

However, for strain 2-151, the combination therapy did not significantly outperform clarithromycin alone, suggesting that the effectiveness of drug combinations can vary depending on the specific strain of bacteria being targeted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activities of rifabutin, clarithromycin, and ethambutol against two virulent strains of Mycobacterium avium in a mouse model. Furney, SK., Skinner, PS., Farrer, J., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Does in vitro susceptibility to rifabutin and ethambutol predict the response to treatment of Mycobacterium avium complex bacteremia with rifabutin, ethambutol, and clarithromycin? Canadian HIV Trials Network Protocol 010 Study Group. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Azithromycin-containing regimens for treatment of Mycobacterium avium complex lung disease. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Activities of azithromycin and clarithromycin against nontuberculous mycobacteria in beige mice. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Impact of clarithromycin and azithromycin on patterns of treatment and survival among AIDS patients with disseminated Mycobacterium avium complex. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Activities of rifabutin, clarithromycin, and ethambutol against two virulent strains of Mycobacterium avium in a mouse model. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Analysis of adverse drug events in pulmonary Mycobacterium avium complex disease using spontaneous reporting system. [2022]

7. China pubmed.ncbi.nlm.nih.gov

Risk for cardiovascular disease in patients with nontuberculous mycobacteria treated with macrolide. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Early-Phase Adverse Effects and Management of Liposomal Amikacin Inhalation for Refractory Mycobacterium avium Complex Lung Disease in Real-World Settings. [2022]

9. Chile pubmed.ncbi.nlm.nih.gov

[Severe neutropenia as side effect of medical treatment in nontuberculous mycobacterial adenitis]. [2015]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Discontinuation rates attributed to adverse events and treatment outcomes between clarithromycin and azithromycin in Mycobacterium avium complex lung disease: A propensity score analysis. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Nontuberculous mycobacterial infections. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Nontuberculous Mycobacterial Pulmonary Disease from Mycobacterium hassiacum, Austria. [2021]

13. Japan pubmed.ncbi.nlm.nih.gov

[Antimycobacterial susceptibility against nontuberculous mycobacteria using brothmic NTM]. [2020]