Clofazimine for Mycobacterium Avium Complex Infection

Not currently recruiting at 6 trial locations

Overseen By Daniel Bouchat

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Oregon Health and Science University

Must not be taking: Bedaquiline, Macrolide, Ethambutol, others

Disqualifiers: Cavitary NTM, Advanced lung disease, HIV, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness and safety of clofazimine (also known as Lamprene) in treating lung disease caused by Mycobacterium avium complex (MAC). Participants will receive either the experimental drug, clofazimine, or a placebo (a sugar pill with no active medicine). Eligible individuals must have had at least two positive MAC tests in the past year and meet specific lung disease criteria. The trial seeks participants not currently on certain MAC treatments and who can consent to participate. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining this trial, especially if you are currently using specific antibiotics or medications that affect heart rhythm. It's best to discuss your current medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that clofazimine is likely to be safe for humans?

Research has shown that clofazimine is generally safe for treating Mycobacterium avium complex (MAC) lung infections. Studies have found that patients using clofazimine as part of their treatment experienced good results without serious side effects. It has been beneficial for individuals who cannot tolerate or do not respond to other treatments.

Clofazimine is often combined with other drugs like amikacin and clarithromycin. This combination has proven effective against certain bacterial lung infections. Specifically, the treatment has shown positive results in individuals with severe MAC lung disease, with no major safety issues reported.

Overall, clofazimine appears to be a well-tolerated option for managing this type of lung infection. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MAC?

Most treatments for Mycobacterium Avium Complex (MAC) infections involve a combination of antibiotics like clarithromycin, rifampin, and ethambutol. However, clofazimine is unique because it has a different mechanism of action, targeting the bacterial cell membrane and interfering with its growth. Researchers are excited about clofazimine because it offers a potential new weapon against MAC infections, especially for patients who may not respond well to the current standard antibiotics. Additionally, clofazimine's ability to penetrate cells and tissues might help effectively clear infections that are difficult to treat with existing options.

What evidence suggests that clofazimine might be an effective treatment for Mycobacterium avium complex?

Research has shown that clofazimine is a promising treatment for Mycobacterium avium complex (MAC) lung disease. Studies have found that combining clofazimine with other antibiotics, such as clarithromycin, can greatly reduce bacterial levels in patients. One study specifically noted that adding clofazimine to the treatment plan significantly decreased the bacteria causing the disease. In this trial, participants will receive either clofazimine or a placebo to further evaluate its effectiveness when used alone. Despite some uncertainty about its standalone efficacy, clofazimine remains an important option for treating severe MAC lung infections. ^{2 6 7 8 9}

Who Is on the Research Team?

Kevin L Winthrop, MD, MPH

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

Adults over 18 with pulmonary Mycobacterium Avium Complex (MAC) infection, who've had at least two positive MAC sputum cultures in the past year are eligible. They must be able to consent and not have severe lung disease, HIV, active tuberculosis or cancer treatments within a year, high heart rhythm risk (QT prolongation), or use certain drugs.

Inclusion Criteria

Ability to provide informed consent for the use of study drug

My lung condition meets specific health standards.

At least 2 positive MAC sputum cultures in the last 12 months with at least one obtained within 12 weeks prior to randomization

Exclusion Criteria

Pregnancy, or breastfeeding that will continue during treatment

Corrected QT (QTc) interval on electrocardiogram (ECG) > 470 ms for females or 450 ms for males, calculated using Fridericia's formula60,61

I am not taking any medications that can affect my heart's rhythm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either clofazimine or placebo for 6 months

24 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Clofazimine

Trial Overview The trial is testing clofazimine's effectiveness and safety against a sugar pill for treating MAC lung disease. Participants will randomly receive either clofazimine or a placebo to compare outcomes between the two groups.

How Is the Trial Designed?

Group I: clofazimine Experimental Treatment 1 Intervention

Participants receive lamprene

Group II: sugar pill Placebo Group 1 Intervention

Participants receive placebo

Clofazimine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Lamprene for:

• Leprosy

Approved in European Union as Lamprene for:

• Leprosy

Approved in Canada as Clofazimine for:

• Leprosy

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

The University of Texas Health Science Center at Tyler

Collaborator

Trials

15

Recruited

25,700+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Temple University

Collaborator

Trials

321

Recruited

89,100+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

National Jewish Health

Collaborator

Trials

145

Recruited

318,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10849115/

Treatment Outcomes of Clofazimine-Containing Regimens in ... Clofazimine demonstrated a favorable treatment outcome in severe Mycobacterium avium complex pulmonary disease. There was no significant ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924857923003503

Efficacy of clofazimine-containing regimens for treatment ... Clofazimine (CFZ) is considered a promising drug for MAC-PD treatment and is frequently included in alternative regimens; however, its efficacy remains unclear.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40948420/

Comparing clinical outcomes of antibiotics for treating ... Although clarithromycin plus clofazimine appears to be the most effective regimen, other clofazimine-based regimens should not be considered as ...

4. journals.asm.org journals.asm.org/doi/10.1128/aac.01853-24

The efficacy of a regimen comprising clarithromycin ... The triple-drug regimen of clarithromycin + clofazimine + bedaquiline was the most effective, achieving a 3.3 log 10 CFU reduction in bacterial load.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02968212

Clofazimine in the Treatment of Pulmonary Mycobacterium ... The purpose of this study is to evaluate the clinical effectiveness and safety of clofazimine when used to treat Mycobacteria avium complex (MAC) lung disease.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25620390/

Safety and tolerability of clofazimine as salvage therapy for ... Clofazimine appears safe and may be considered as a salvage therapeutic option in SOT recipients with MAC infection who are intolerant or unresponsive to ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1341321X2500220X

Clinical considerations of the safety and efficacy ... Clofazimine (CFZ) has been shown to exhibit synergism with amikacin and clarithromycin against nontuberculous mycobacteria (NTM), ...

8. academic.oup.com academic.oup.com/ofid/article/11/2/ofad682/7502877

Treatment Outcomes of Clofazimine-Containing Regimens in ... Clofazimine demonstrated a favorable treatment outcome in severe Mycobacterium avium complex pulmonary disease. There was no significant ...

9. emedicine.medscape.com emedicine.medscape.com/article/222664-treatment

Mycobacterium Avium Complex (MAC) ... In general, MAC infection is treated with daily dosing of three antimicrobials for at least 12 months after sputum culture conversion.