What side effects are associated with this type of intervention?

The most common treatments for Pulmonary Mycobacterium avium complex (MAC) infection include clarithromycin, ethambutol, and rifampicin. Clarithromycin can cause gastrointestinal disturbances, taste disturbances, and, less commonly, hepatotoxicity and QT prolongation. Ethambutol may lead to optic neuritis, which can result in vision changes, and peripheral neuropathy. Rifampicin is known for causing hepatotoxicity, gastrointestinal upset, and red-orange discoloration of bodily fluids. Aminoglycosides like kanamycin, when used, can cause nephrotoxicity and ototoxicity, leading to kidney damage and hearing loss, respectively. These side effects necessitate careful monitoring during treatment.

What prior FDA approvals exist?

The FDA has approved several antibiotics for the treatment of Pulmonary Mycobacterium avium complex (MAC) infection, often used in combination to enhance efficacy and prevent resistance. Key drugs include macrolides like clarithromycin, ethambutol, and rifabutin. Aminoglycosides such as amikacin and kanamycin are also used in certain regimens. These treatments aim to target and manage MAC lung infections effectively.

What other types of research exist?

Promising alternatives to RHB-204 for treating Pulmonary MAC infection include: 1) Clarithromycin-based regimens, often combined with ethambutol and rifabutin, which have shown improved survival rates. 2) Multidrug antibiotic therapy including clarithromycin, ethambutol, rifampicin, amikacin, and moxifloxacin, which has been effective in cases of clarithromycin-resistant MAC. 3) Novel beta-lactamase-inhibitor combinations like ceftazidime-avibactam, which may be effective against multidrug-resistant organisms, though clinical data is sparse. Consultation with an infectious disease specialist is recommended for personalized treatment planning.

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Antibiotic

RHB-204 for MAC Lung Infection (CleaR-MAC Trial)

Phase 3

Waitlist Available

Research Sponsored by RedHill Biopharma Limited

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have symptoms of MAC lung infection that include one of the following: respiratory symptoms such as chronic cough, excessive mucous production, fatigue, dyspnea, hemoptysis or systemic symptoms such as fever, night sweats or loss of appetite.

Have a MAC lung infection documented by one MAC positive culture within 18 months prior to screening and a MAC positive culture at screening (cultures need to be at least 1 month apart).

Must not have

Currently taking or treated in the 6 months prior to screening with any of the following: bedaquiline, clofazimine or any component of American Thoracic Society(ATS)/Infectious Diseases Society of America (IDSA) multi-drug recommended therapy (macrolides, ethambutol, rifabutins/rifampins) for MAC or other multi-drug regime for NTM lung disease

History of ventricular arrhythmias or family history of Long QT syndrome, including torsades de pointes

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 19 months

Awards & highlights

All Individual Drugs Already Approved

Approved for 10 Other Conditions

Pivotal Trial

Summary

This trial tests RHB-204, a new medication, in adults with a specific lung condition and bacterial infection. It aims to see if the drug can clear the infection and improve patients' quality of life by reducing symptoms.

Who is the study for?

Adults aged 18-85 with MAC lung infection, showing symptoms like chronic cough or night sweats, and not treated for MAC in the last 6 months can join. They must weigh over 90 pounds and have a CT scan showing specific lung changes within the past 6 months.

What is being tested?

The trial is testing RHB-204 against a placebo to see if it's effective and safe for treating pulmonary Mycobacterium Avium Complex disease. Participants are randomly assigned to either the drug or placebo group in a double-blind setup.

What are the potential side effects?

While specific side effects of RHB-204 aren't listed here, common ones may include digestive issues, potential allergic reactions, liver enzyme changes, and possibly others as seen with antibiotics used for similar infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have symptoms like chronic cough, fatigue, or night sweats due to a MAC lung infection.

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I have had two positive MAC lung infection tests at least a month apart, one within the last 18 months.

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I weigh more than 90 pounds.

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I have had two positive tests for MAC lung infection, one within the last 18 months and another at screening.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated for lung disease with specific drugs in the last 6 months.

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I have a history of irregular heartbeats or a family history of Long QT syndrome.

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I am scheduled for lung surgery due to MAC lung disease.

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My infection is resistant to standard antibiotics.

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I need to use supplemental oxygen regularly.

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I am currently using an inhaled medication that contains amikacin, tobramycin, or gentamicin.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 19 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~19 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 19 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Quality of Life Questionnaire - Bronchiectasis (QoL B) Respiratory Symptoms domain score from baseline to Month 6 for RHB-204 compared to placebo

Sputum culture conversion (SCC)

Secondary study objectives

Part 1 Secondary efficacy objective - Improvement in Physical Functioning

Part 1 Secondary efficacy objective - Reduction of fatigue

Part 1 Secondary efficacy objective - Time to culture conversion

+8 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: RHB-204Experimental Treatment1 Intervention

Each capsule contains clarithromycin 158.3mg; rifabutin 40mg; clofazimine 13.3mg.

Group II: PlaceboPlacebo Group1 Intervention

Matching placebo will contain riboflavin, a type of B vitamin, which may discolor urine in a similar fashion as RHB-204.

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Pulmonary Mycobacterium avium complex (MAC) Infection include macrolides (clarithromycin, azithromycin), ethambutol, and rifamycins (rifampin, rifabutin). Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit, which is crucial for stopping the growth of MAC bacteria. Ethambutol works by inhibiting the synthesis of the bacterial cell wall, making it easier for other antibiotics to penetrate and kill the bacteria. Rifamycins inhibit bacterial RNA synthesis by binding to the DNA-dependent RNA polymerase, which is essential for bacterial replication. These mechanisms are important for Pulmonary MAC Infection patients because they target different aspects of bacterial growth and survival, making the treatment more effective and reducing the risk of antibiotic resistance.

Streptococcal M1 protein-provoked CXC chemokine formation, neutrophil recruitment and lung damage are regulated by Rho-kinase signaling.Rho-kinase regulates adhesive and mechanical mechanisms of pulmonary recruitment of neutrophils in abdominal sepsis.Macrolides reduce the expression of surface Mac-1 molecule on neutrophil.