ALIS for Nontuberculous Mycobacterial Infections

(ENCORE Trial)

Not currently recruiting at 371 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new inhaled treatment called ALIS for individuals with lung infections caused by Mycobacterium avium complex (MAC). The goal is to determine if ALIS, combined with azithromycin and ethambutol, improves breathing symptoms over a year. Participants will receive either the ALIS treatment or a placebo (a substance with no active ingredients) alongside the two other medicines. Individuals with a current MAC lung infection, no more than three past infections, and no prior treatment for the current infection may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that ALIS (Amikacin Liposome Inhalation Suspension) is safe to use. Research indicates that adding ALIS to standard treatments was effective and well-tolerated in a small group of patients with difficult lung infections. ALIS is designed for inhalation, which helps prevent most of the drug from spreading throughout the body, potentially reducing side effects.

Azithromycin and ethambutol, part of the standard treatment plan, are commonly used antibiotics for lung infections. They are considered safe due to their widespread use in many cases. Overall, the treatments in this trial are deemed safe based on past studies and general medical use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for nontuberculous mycobacterial (NTM) infections, which typically include combinations of oral antibiotics like azithromycin, ethambutol, and rifampin, ALIS (amikacin liposome inhalation suspension) offers a novel delivery method using inhalation. This approach allows the drug to be delivered directly to the lungs, where NTM infections primarily occur, potentially increasing the drug's effectiveness while minimizing systemic side effects. Researchers are excited because this targeted delivery could improve treatment outcomes and reduce the treatment duration compared to traditional oral regimens. Additionally, ALIS uses liposome technology to encapsulate amikacin, which may enhance the drug's penetration into infected cells.

What evidence suggests that this trial's treatments could be effective for nontuberculous mycobacterial infections?

Research has shown that adding ALIS, an inhaled medication, to standard treatments effectively aids patients with difficult-to-treat lung infections caused by certain bacteria. In this trial, some participants will receive ALIS alongside a background regimen of azithromycin and ethambutol. One study found that patients, particularly those with nodular bronchiectatic disease, improved significantly, with 84.2% achieving culture conversion, meaning the bacteria were no longer present in their samples. ALIS works by penetrating protective layers around the bacteria and helping the medicine remain longer in the lungs where it's needed. Clinical guidelines recommend ALIS for patients with resistant Mycobacterium avium complex infections. These findings suggest ALIS could be a promising addition for managing these lung infections. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39459407/

Amikacin Liposomal Inhalation Suspension for Non- ... Adding ALIS to standard regimens was effective and safe in a small group of Greek patients with refractory or recurrent NTM lung disease.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04677569

NCT04677569 | Study to Evaluate ALIS (Amikacin ... The main objective of this study is to evaluate the efficacy of ALIS (amikacin liposome inhalation suspension) + background regimen (azithromycin [AZI] + ...

3. frontiersin.org frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.00915/full

Amikacin Liposome Inhalation Suspension (ALIS ... ALIS effectively penetrates NTM biofilms, enhances amikacin uptake into macrophages, both in vitro and in vivo, and retains amikacin within airways and lung ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0954611125004718

Real-world effectiveness and Lung Abnormalities ... The guideline recommends the addition of amikacin liposome inhalation suspension (ALIS) for patients with refractory Mycobacterium avium complex ...

5. academic.oup.com academic.oup.com/ofid/article/12/3/ofaf118/8046251

Effects of Amikacin Liposome Inhalation Suspension and ... ALIS efficacy in 44 refractory MAC-PD patients was higher in nodular bronchiectatic (84.2% culture conversion) than cavitary (36.0%) subtypes. High CRP lev.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9279646/

Safety and Outcomes of Amikacin Liposome Inhalation ... Amikacin liposome inhalation suspension (ALIS) allows for better biofilm and macrophage penetration and is likely more effective than inhalation of the IV ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0012369221007030

Amikacin Liposome Inhalation Suspension for Refractory ... Amikacin liposome inhalation suspension (ALIS; Arikayce) was developed for nebulized administration to limit systemic amikacin exposure while increasing uptake ...

8. journal.chestnet.org journal.chestnet.org/article/S0012-3692(22)00051-4/pdf

Safety and Outcomes of Amikacin Liposome Inhalation ... Amikacin liposome inhalation suspension (ALIS) allows for better biofilm and macrophage penetration3 and is likely more effective than inhalation of the IV ...