CLINICAL TRIALS PROFILE FOR BENZNIDAZOLE

505(b)(2) Clinical Trials for BENZNIDAZOLE

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Dosage	NCT03981523 ↗	New Therapies and Biomarkers for Chagas Infection	Active, not recruiting	Barcelona Institute for Global Health	Phase 2	2019-12-18	Chagas disease (CD) is an endemic zoonotic disease with a significant global impact. Current approved treatments for CD (benznidazole (BZN) and nifurtimox (NFX)) were developed in the 1970s with regimens and dosing intervals derived from decades-old patient series and with very limited direct comparisons. Treatment recommendations vary significantly from country to country and the comparative evidence-base with the current treatment regimens is limited. The reported efficacy of both drugs in patients with T. cruzi infection is variable and depends on the disease stage, the drug dose, the age of patients, and the infecting T. cruzi strain or genotype. Due to a therapeutic failure of at least 20% after 12 months in chronic patients and the high rate of adverse events, together with the recent data that suggest that we may be overdosing patients, we propose to test new dosing regimens of these two old compounds. Hypotheses: - Lowering the frequency of drug dosing of BZN and NFX, the plasma drug levels of the drugs within the therapeutic range will be maintained. - The duration of treatment with BZN or NFX may be related to the effectiveness of these drugs. - Blood levels of the proposed biomarkers will significantly diminish or became negative after a relatively short interval after treatment.
New Dosage	NCT03981523 ↗	New Therapies and Biomarkers for Chagas Infection	Active, not recruiting	Drugs for Neglected Diseases	Phase 2	2019-12-18	Chagas disease (CD) is an endemic zoonotic disease with a significant global impact. Current approved treatments for CD (benznidazole (BZN) and nifurtimox (NFX)) were developed in the 1970s with regimens and dosing intervals derived from decades-old patient series and with very limited direct comparisons. Treatment recommendations vary significantly from country to country and the comparative evidence-base with the current treatment regimens is limited. The reported efficacy of both drugs in patients with T. cruzi infection is variable and depends on the disease stage, the drug dose, the age of patients, and the infecting T. cruzi strain or genotype. Due to a therapeutic failure of at least 20% after 12 months in chronic patients and the high rate of adverse events, together with the recent data that suggest that we may be overdosing patients, we propose to test new dosing regimens of these two old compounds. Hypotheses: - Lowering the frequency of drug dosing of BZN and NFX, the plasma drug levels of the drugs within the therapeutic range will be maintained. - The duration of treatment with BZN or NFX may be related to the effectiveness of these drugs. - Blood levels of the proposed biomarkers will significantly diminish or became negative after a relatively short interval after treatment.
New Dosage	NCT03981523 ↗	New Therapies and Biomarkers for Chagas Infection	Active, not recruiting	Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente (CEADES)	Phase 2	2019-12-18	Chagas disease (CD) is an endemic zoonotic disease with a significant global impact. Current approved treatments for CD (benznidazole (BZN) and nifurtimox (NFX)) were developed in the 1970s with regimens and dosing intervals derived from decades-old patient series and with very limited direct comparisons. Treatment recommendations vary significantly from country to country and the comparative evidence-base with the current treatment regimens is limited. The reported efficacy of both drugs in patients with T. cruzi infection is variable and depends on the disease stage, the drug dose, the age of patients, and the infecting T. cruzi strain or genotype. Due to a therapeutic failure of at least 20% after 12 months in chronic patients and the high rate of adverse events, together with the recent data that suggest that we may be overdosing patients, we propose to test new dosing regimens of these two old compounds. Hypotheses: - Lowering the frequency of drug dosing of BZN and NFX, the plasma drug levels of the drugs within the therapeutic range will be maintained. - The duration of treatment with BZN or NFX may be related to the effectiveness of these drugs. - Blood levels of the proposed biomarkers will significantly diminish or became negative after a relatively short interval after treatment.

All Clinical Trials for BENZNIDAZOLE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00123916 ↗	BENEFIT: Evaluation of the Use of Antiparasital Drug (Benznidazole) in the Treatment of Chronic Chagas' Disease	Completed	Canadian Institutes of Health Research (CIHR)	Phase 3	2004-11-01	Evaluate if benznidazole, an antiparasite drug, given at a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 to 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg) - reduces morbidity and mortality in patients with Chronic Chagas' Cardiomyopathy (CCC). The BENEFIT study is being conducted by the Population Health Research Institute (in Hamilton, Canada) and the Institute Dante Pazzanese de Cardiologia (Sao Paulo, Brazil) together with a Steering Committee, and an independent Safety Monitoring Board.
NCT00123916 ↗	BENEFIT: Evaluation of the Use of Antiparasital Drug (Benznidazole) in the Treatment of Chronic Chagas' Disease	Completed	Instituto Dante Pazzanese de Cardiologia	Phase 3	2004-11-01	Evaluate if benznidazole, an antiparasite drug, given at a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 to 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg) - reduces morbidity and mortality in patients with Chronic Chagas' Cardiomyopathy (CCC). The BENEFIT study is being conducted by the Population Health Research Institute (in Hamilton, Canada) and the Institute Dante Pazzanese de Cardiologia (Sao Paulo, Brazil) together with a Steering Committee, and an independent Safety Monitoring Board.
NCT00123916 ↗	BENEFIT: Evaluation of the Use of Antiparasital Drug (Benznidazole) in the Treatment of Chronic Chagas' Disease	Completed	University of Sao Paulo	Phase 3	2004-11-01	Evaluate if benznidazole, an antiparasite drug, given at a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 to 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg) - reduces morbidity and mortality in patients with Chronic Chagas' Cardiomyopathy (CCC). The BENEFIT study is being conducted by the Population Health Research Institute (in Hamilton, Canada) and the Institute Dante Pazzanese de Cardiologia (Sao Paulo, Brazil) together with a Steering Committee, and an independent Safety Monitoring Board.

Clinical Trial Conditions for BENZNIDAZOLE

Condition Name

Condition Name for BENZNIDAZOLE
Intervention	Trials
Chagas Disease	17
Trypanosoma Cruzi Infection	2
Trypanosomiasis	1

Condition MeSH

Condition MeSH for BENZNIDAZOLE
Intervention	Trials
Chagas Disease	20
Trypanosomiasis	3
Inflammation	1

Clinical Trial Locations for BENZNIDAZOLE

Trials by Country

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−

Trials by Country for BENZNIDAZOLE
Location	Trials
Argentina	20
Brazil	13
Bolivia	10
Colombia	5
Spain	5

Trials by US State

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−

Trials by US State for BENZNIDAZOLE
Location	Trials
Louisiana	1
California	1

Clinical Trial Progress for BENZNIDAZOLE

Clinical Trial Phase

Clinical Trial Phase for BENZNIDAZOLE
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	5
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for BENZNIDAZOLE
Clinical Trial Phase	Trials
Completed	11
Unknown status	5
Recruiting	4

Clinical Trial Sponsors for BENZNIDAZOLE

Sponsor Name

Sponsor Name for BENZNIDAZOLE
Sponsor	Trials
Drugs for Neglected Diseases	8
Hospital Universitari Vall d'Hebron Research Institute	2
Barcelona Centre for International Health Research	2

Sponsor Type

Sponsor Type for BENZNIDAZOLE
Sponsor	Trials
Other	51
Industry	6
NIH	1

Benznidazole: Clinical Trials, Market Analysis, and Projections

Introduction

Benznidazole is the standard treatment for Chagas disease, a parasitic infection caused by Trypanosoma cruzi that affects millions of people, particularly in Latin America. Despite its efficacy, benznidazole has significant limitations, including a long treatment duration and substantial side effects. This article will delve into the latest clinical trials, market analysis, and projections for benznidazole, highlighting efforts to improve its safety, efficacy, and patient adherence.

Current Clinical Trials and Studies

BENDITA Study

The BENDITA (Benznidazole New Doses Improved Treatment & Therapeutic Associations) study, conducted by the Drugs for Neglected Diseases initiative (DNDi), aimed to evaluate new therapeutic regimens of benznidazole. This Phase II study, carried out from 2016 to 2018 in Bolivia, tested six different benznidazole treatments, including monotherapy and combination with fosravuconazole, against a placebo. The results showed that shorter regimens, particularly a two-week course of benznidazole monotherapy, were effective and had fewer side effects compared to the standard eight-week treatment[1].

MULTIBENZ Trial

The MULTIBENZ trial, an international Phase 2b study, compared the parasitological efficacy and safety of three different benznidazole regimens in adult patients with chronic Chagas disease. The study found that reducing the treatment duration from 60 days to 15 days maintained similar parasitological responses while improving adherence and reducing discontinuations due to side effects[4].

NuestroBen Study

Following the positive results from the BENDITA study, DNDi and its partners initiated the NuestroBen study, a Phase III clinical trial in Argentina. This study aims to compare the safety and efficacy of 2-week and 4-week regimens of benznidazole against the standard 8-week regimen in adults with chronic Chagas disease. The study was reinitiated in 2023 after receiving ethical and regulatory approvals, with recruitment expected to continue until the first quarter of 2025[1][5].

Market Analysis

Market Drivers

The Chagas disease treatment market is driven by several key factors:

• Increase in R&D Activities: Efforts to develop novel treatments and approval of new products are boosting the market.
• Prevalence of Chagas Disease: The rise in the number of people affected by Chagas disease, partly due to unhygienic conditions, is a significant driver.
• Population Growth: An increase in the population affected by Chagas disease is contributing to market growth[2].

Market Restraints

Despite the growth drivers, the market faces several challenges:

• Supply Chain Issues: Problems in the supply chain of Chagas disease drugs hinder market expansion.
• Lack of Awareness: Limited awareness about Chagas disease treatment among patients and healthcare providers is a restraint.
• Limited Approved Products: The current market has a limited number of approved products, which restricts growth[2].

Market Segmentation

The Chagas disease treatment market is segmented based on:

• Treatment Type: Antiparasitic treatment and symptomatic treatment.
• Drug Type: Benznidazole and nifurtimox.
• Distribution Channel: Hospital pharmacies, online pharmacies, and retail pharmacies.
• Region: North America, Europe, Asia-Pacific, and LAMEA (Latin America, Middle East, and Africa)[2].

Market Projections

Growth Forecast

The global Chagas disease treatment market is expected to grow significantly due to the increasing prevalence of the disease and ongoing R&D activities. The market is anticipated to expand as new treatments and vaccines are developed and approved. Key players such as Bayer AG, AstraZeneca, and GlaxoSmithKline are expected to enter the market with new products, further driving growth[2].

Regional Analysis

The market analysis across different regions provides insights into current trends and future market potential. The LAMEA region, where Chagas disease is most prevalent, is expected to be a significant market for benznidazole and other Chagas disease treatments. Strategic regional plans by companies will be crucial in capturing this market[2].

Safety and Efficacy Improvements

Reduced Treatment Duration

Studies have shown that shorter treatment regimens of benznidazole can maintain efficacy while reducing side effects and improving patient adherence. For example, the BENDITA study found that an 83% efficacy rate was achieved with a two-week course of benznidazole monotherapy, with no patients discontinuing treatment due to side effects[1].

Combination Therapies

Combination therapies with fosravuconazole are also being explored to enhance the safety and efficacy of benznidazole. These combinations have shown promising results in reducing side effects and improving treatment outcomes[1].

Future Directions

New Drug Candidates

DNDi and its partners are working on discovering and developing entirely new drug candidates for Chagas disease. The development of DNDI-6148, for instance, is ongoing, although it has been paused pending further studies on potential reproductive toxicity. Oxaboroles are also being assessed as potential new candidates[5].

Test-and-Treat Strategies

Efforts are being made to roll out ‘test-and-treat’ strategies to reach people living with Chagas disease in remote areas of Latin America. This approach aims to reduce mother-to-child transmission and improve treatment coverage[5].

Key Takeaways

• Clinical Trials: Ongoing and planned clinical trials, such as the BENDITA and NuestroBen studies, are focused on improving the safety and efficacy of benznidazole regimens.
• Market Growth: The Chagas disease treatment market is expected to grow driven by R&D activities, increasing prevalence, and new product approvals.
• Regional Focus: The LAMEA region is a key market due to the high prevalence of Chagas disease.
• Safety Improvements: Shorter treatment regimens and combination therapies are being explored to reduce side effects and improve patient adherence.
• Future Directions: New drug candidates and test-and-treat strategies are being developed to address the limitations of current treatments.

FAQs

What are the main limitations of the current benznidazole treatment for Chagas disease?

The main limitations include a long treatment duration of 60 days and significant side effects, such as gastric intolerance, skin rashes, and neuromuscular problems, which lead to about 20% of patients discontinuing treatment[1].

What are the key findings of the BENDITA study?

The BENDITA study found that a two-week course of benznidazole monotherapy was as effective as the standard eight-week treatment and had fewer side effects, with no patients discontinuing treatment due to side effects[1].

What is the NuestroBen study, and what is its objective?

The NuestroBen study is a Phase III clinical trial in Argentina that aims to compare the safety and efficacy of 2-week and 4-week regimens of benznidazole against the standard 8-week regimen in adults with chronic Chagas disease[1][5].

How is the Chagas disease treatment market segmented?

The market is segmented based on treatment type, drug type, distribution channel, and region. Key segments include antiparasitic treatment, benznidazole, hospital pharmacies, and the LAMEA region[2].

What are the future directions for Chagas disease treatment?

Future directions include the development of new drug candidates, such as DNDI-6148 and oxaboroles, and the implementation of ‘test-and-treat’ strategies to reduce mother-to-child transmission and improve treatment coverage[5].

Sources

1. DNDi: New benznidazole regimens - DNDi
2. Allied Market Research: Chagas Disease Treatment Market Size, Share and Trends | 2019
3. Biospace: U.S. Clinical Trials Market Size Industry Analysis Report, 2033
4. PubMed: Efficacy of three benznidazole dosing strategies for adults living with ...
5. DNDi: 2023 R&D portfolio in review: Chagas - DNDi