CLINICAL TRIALS PROFILE FOR CLOFAZIMINE

All Clinical Trials for Clofazimine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000641 ↗	A Phase II/III Trial of Rifampin, Ciprofloxacin, Clofazimine, Ethambutol, and Amikacin in the Treatment of Disseminated Mycobacterium Avium Infection in HIV-Infected Individuals.	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To compare the effectiveness and toxicity of two combination drug treatment programs for the treatment of disseminated Mycobacterium avium infection in HIV seropositive patients. [Per 03/06/92 amendment: to evaluate the efficacy of azithromycin when given in conjunction with either ethambutol or clofazimine as maintenance therapy.] Disseminated M. avium infection is the most common systemic bacterial infection complicating AIDS in the United States. The prognosis of patients with disseminated M. avium is extremely poor, particularly when it follows other opportunistic infections or is associated with anemia. Test tube studies and clinical data indicate that the best treatment program may include clofazimine, ethambutol, a rifamycin derivative, and ciprofloxacin. Test tube and animal studies indicate that amikacin is a bactericidal (bacteria destroying) drug that works better when used with ciprofloxacin. Its role in treatment programs is a key issue because of toxicity and because it must be administered parenterally (by injection or intravenously).
NCT00000796 ↗	A Prospective Study of Multidrug Resistance and a Pilot Study of the Safety of and Clinical and Microbiologic Response to Levofloxacin in Combination With Other Antimycobacterial Drugs for Treatment of Multidrug-Resistant Pulmonary Tuberculosis (MDR	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To determine the demographic, behavioral, clinical, and geographic risk factors associated with the occurrence of multidrug-resistant pulmonary tuberculosis (MDRTB). To evaluate the clinical and microbiological responses and overall survival of MDRTB patients who are treated with levofloxacin-containing multiple-drug regimens chosen from a hierarchical list. Per 9/28/94 amendment, to assess whether persistent or recurrent positive sputum cultures of patients who show failure or relapse are due to the same strain or reinfection with a new strain. Among TB patients, there has been an increase in progressive disease due to the emergence of antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify patients at high risk for MDRTB increases the hazard for both treatment failure and development of resistance to additional therapeutic agents. Efforts to improve survival in patients with MDRTB will depend on improved methods of assessing the risk of acquisition of MDRTB and identifying drug susceptibility patterns in a timely fashion.
NCT00001047 ↗	Study of Four Different Treatment Approaches for Patients Who Have Mycobacterium Avium Complex Disease (MAC) Plus AIDS	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To compare the safety and efficacy of two doses of clarithromycin in combination with ethambutol and either rifabutin or clofazimine for the treatment of disseminated Mycobacterium avium Complex (MAC) disease in AIDS patients. Recommendations have been issued for AIDS patients with disseminated MAC to be treated with at least two antimycobacterial agents and for every regimen to include a macrolide (clarithromycin or azithromycin). However, the optimal treatment for disseminated MAC remains unknown.
NCT00001058 ↗	A Comparison of Three Drug Combinations Containing Clarithromycin in the Treatment of Mycobacterium Avium Complex (MAC) Disease in Patients With AIDS	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To compare the efficacy and safety of clarithromycin combined with rifabutin, ethambutol, or both in the treatment of disseminated Mycobacterium avium Complex (MAC) disease in persons with AIDS, including individuals who have or have not received prior MAC prophylaxis. It is believed that effective therapy for MAC disease in patients with AIDS requires combinations of two or more antimycobacterial agents in order to overcome drug resistance and the unfavorable influence of the profound immunosuppression associated with AIDS. Data suggest that clarithromycin may have substantial activity in two- or three-drug combination regimens with clofazimine, rifamycin derivatives, ethambutol, or the 4-quinolones.
NCT00002058 ↗	A Randomized Controlled Prophylactic Study of Clofazimine To Prevent Mycobacterium Avium Complex Infection in HIV Disease	Completed	University of California, San Francisco	N/A	1969-12-31	This study will examine the effectiveness of clofazimine in the prophylaxis of Mycobacterium avium complex infection in HIV infected individuals who are at risk to develop this untreatable opportunistic disease. In the absence of truly effective antiretroviral therapy, a potential mode of treatment of patients with HIV infection is to prevent the development of the life-threatening opportunistic infections. Current studies demonstrate a possible efficacy of clofazimine in the prophylaxis against Pneumocystis carinii pneumonia (PCP), the most common AIDS-defining opportunistic infection. Future studies will examine the potential for prophylaxis against the other opportunistic infections. This proposal hopes to define the role of prophylactic clofazimine in preventing the currently untreatable Mycobacterium avium complex infection. AMENDED: To include prophylaxis for Asymptomatic and ARC.

Clinical Trial Conditions for Clofazimine

Condition Name

Condition Name for Clofazimine
Intervention	Trials
Tuberculosis	7
Tuberculosis, Multidrug-Resistant	6
HIV Infections	6
Tuberculosis, Pulmonary	5

Condition MeSH

Condition MeSH for Clofazimine
Intervention	Trials
Tuberculosis	26
Tuberculosis, Multidrug-Resistant	17
Tuberculosis, Pulmonary	15
Mycobacterium Infections	10

Clinical Trial Locations for Clofazimine

Trials by Country

Trials by Country for Clofazimine
Location	Trials
United States	62
China	51
South Africa	22
Uzbekistan	7
India	6

Trials by US State

Trials by US State for Clofazimine
Location	Trials
California	6
New York	5
Illinois	5
Pennsylvania	4
Maryland	4

Clinical Trial Progress for Clofazimine

Clinical Trial Phase

Clinical Trial Phase for Clofazimine
Clinical Trial Phase	Trials
Phase 4	8
Phase 3	8
Phase 2/Phase 3	6

Clinical Trial Status

Clinical Trial Status for Clofazimine
Clinical Trial Phase	Trials
Recruiting	18
Completed	12
Not yet recruiting	7

Clinical Trial Sponsors for Clofazimine

Sponsor Name

Sponsor Name for Clofazimine
Sponsor	Trials
National Institute of Allergy and Infectious Diseases (NIAID)	8
Ministry of Health, Republic of Uzbekistan	5
Medecins Sans Frontieres, Netherlands	5

Sponsor Type

Sponsor Type for Clofazimine
Sponsor	Trials
Other	201
Industry	10
NIH	9

Clofazimine: Clinical Trials Update, Market Analysis, and Projections

Introduction

Clofazimine is a crucial antibiotic used primarily in the treatment of tuberculosis (TB), particularly in cases of drug-resistant TB, and increasingly being explored for other mycobacterial infections. Here, we will delve into the latest updates on clinical trials, market analysis, and future projections for this drug.

Clinical Trials Update

Drug-Sensitive TB Trials

A recent clinical trial, known as the Clo-Fast (ACTG A5362; NCT04311502) study, aimed to evaluate the safety and efficacy of a 3-month regimen containing clofazimine and rifapentine for drug-susceptible TB. However, the trial was stopped early due to lack of clinical efficacy. The results showed that while culture conversion rates were high in both the experimental and standard of care arms, the experimental arm had a higher rate of adverse events, particularly related to kidney function[1].

Nontuberculous Mycobacterial (NTM) Lung Disease Trials

MannKind Corporation has initiated a Phase 3 clinical trial, ICoN-1, to evaluate the efficacy and safety of Clofazimine Inhalation Suspension for the treatment of NTM lung disease. This multi-national, randomized, double-blind, placebo-controlled study aims to enroll approximately 230 participants and assess outcomes such as sputum culture conversion and quality of life improvements. The trial has been cleared by health authorities in several countries, including Australia, the U.S., Japan, and South Korea, with Taiwan anticipated to follow[4].

Pharmacokinetics and Dosing Implications

Pharmacokinetic studies on clofazimine have highlighted several important considerations. A study in South African TB patients revealed that clofazimine's disposition is strongly influenced by body fat content, with lower plasma exposures observed in women during the initial months of treatment. This suggests the need for optimized dosing strategies, such as a loading dose, to achieve target efficacy concentrations more quickly[3].

Market Analysis

Current Market Trends

The global clofazimine market has experienced rapid growth in recent years and is projected to continue this trend from 2023 to 2031. The market is segmented by type (pills, powder), application (anti-inflammatory, antimicrobial), and geographical regions (North America, Europe, Asia-Pacific, etc.). Key drivers include increasing demand for effective treatments for TB and other mycobacterial infections, as well as advancements in pharmaceutical formulations[2].

Market Size and Forecast

The market size of clofazimine is expected to grow significantly, with forecasts indicating robust growth rates throughout the forecast period. The report provides a detailed analysis of market dynamics, including drivers, restraints, opportunities, and challenges. It also includes a comprehensive evaluation of the competitive landscape, featuring prominent companies such as Ambeed, Cayman Chemical, and Merck KGaA[2].

Geographical Distribution

The market is geographically diverse, with significant growth anticipated in regions such as Asia-Pacific, driven by high prevalence rates of TB and other mycobacterial infections. North America and Europe are also expected to contribute substantially to the market growth due to advanced healthcare infrastructure and higher adoption rates of new treatments[2].

Projections and Future Outlook

Continued Growth in TB Treatment

Clofazimine is expected to remain a key component in the treatment of drug-resistant TB, driving market growth. However, the need for optimized dosing strategies and better pharmacokinetic data will be crucial for improving treatment outcomes[3].

Expansion into NTM Lung Disease

The ongoing Phase 3 trial by MannKind Corporation for NTM lung disease treatment could significantly expand the market for clofazimine if successful. This would open up new therapeutic avenues and increase demand for the drug[4].

Market Challenges and Opportunities

Despite the positive growth projections, the market faces challenges such as the need for evidence-based dosing recommendations and potential pharmacokinetic interactions with other drugs. However, these challenges also present opportunities for research and development, particularly in optimizing treatment regimens and exploring new formulations like inhalation suspensions[1][3].

Key Takeaways

• Clinical Trials: Recent trials have shown mixed results, with the Clo-Fast study being stopped due to inefficacy, while the ICoN-1 trial for NTM lung disease is ongoing and promising.
• Pharmacokinetics: Body fat content significantly affects clofazimine's pharmacokinetics, necessitating optimized dosing strategies.
• Market Analysis: The global clofazimine market is projected to grow significantly from 2023 to 2031, driven by increasing demand and advancements in pharmaceuticals.
• Future Outlook: The drug is expected to remain crucial in TB treatment and may expand into new therapeutic areas like NTM lung disease.

FAQs

What was the outcome of the Clo-Fast clinical trial for drug-susceptible TB?

The Clo-Fast trial was stopped early due to lack of clinical efficacy, despite high culture conversion rates, and a higher rate of adverse events in the experimental arm[1].

What is the focus of the ICoN-1 clinical trial by MannKind Corporation?

The ICoN-1 trial is evaluating the efficacy and safety of Clofazimine Inhalation Suspension for the treatment of nontuberculous mycobacterial (NTM) lung disease[4].

How does body fat content affect clofazimine's pharmacokinetics?

Body fat content significantly influences clofazimine's disposition, with lower plasma exposures observed in women during the initial months of treatment, suggesting the need for optimized dosing strategies[3].

What are the key drivers of the global clofazimine market growth?

Key drivers include increasing demand for effective treatments for TB and other mycobacterial infections, as well as advancements in pharmaceutical formulations[2].

Which regions are expected to contribute significantly to the growth of the clofazimine market?

Asia-Pacific, North America, and Europe are expected to be significant contributors to the market growth due to high prevalence rates and advanced healthcare infrastructure[2].

Sources

1. Provisional Results From a 3-month Clofazimine/Rifapentine ... - Croiconference.org
2. Global Clofazimine Market Size, Scope And Forecast Report - MarketResearchIntellect.com
3. Clofazimine pharmacokinetics in patients with TB: dosing implications - Academic.oup.com
4. First Site Initiated in Australia for MannKind's Phase 3 Clinical Trial ... - Biospace.com