New Scheme for Treatment With Benznidazole

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Brief Title

New Scheme for Treatment With Benznidazole

Official Title

A Phase III Non-inferiority Study to Confirm the Efficacy and Safety of a New Benznidazole Regimen Compared to Historical Control to Treat Adult Patients in the Chronic Phase of Chagas Disease Without Evidence of Pathology

Brief Summary

      Chagas disease, a parasitic infection caused by Trypanosoma cruzi, is endemic in much of
      Latin America and affects people throughout the world. Currently treatment with the only two
      drugs effective against the infection, benznidazole and nifurtimox, has significant
      limitations including frequent adverse effects in adult patients. However, timely treatment
      is key to achieving global objectives of controlling the disease. The standard treatment has
      a long duration (60 days). NuestroBen will test the hypothesis that a shorter treatment
      regimen of 14 days will be non-inferior to the standard 60-day treatment while improving the
      safety profile.
    

Detailed Description

      Chagas disease is a vector-borne parasitic infection affecting an estimated 6 million people
      worldwide. Very few people have been able to access antiparasitic treatment for the disease,
      and about 20% of those who do initiate treatment are unable to complete it due to the long
      duration (2 months) and side effects associated with the current regimen. Benznidazole is one
      of only two drugs with proven efficacy against Trypanosoma cruzi, the parasite that causes
      the disease. An earlier Phase 2 clinical trial, BENDITA, indicated 89% of 30 patients treated
      with a shorter (2-week) regimen of benznidazole maintained sustained parasite clearance after
      12 months of follow-up, with no discontinuations of treatment due to side effects. The
      current study will evaluate the shorter treatment regimen with benznidazole in a Phase III
      clinical trial. NuestroBen will assess the efficacy and safety of a 2-week regimen of BZN
      (300 mg daily), compared to the standard treatment of BZN 5mg/kg/day or 300-400 mg daily
      fixed doses for 8 weeks based on historical controls, in terms of reducing and eliminating
      the T. cruzi parasite in adults in the chronic phase of Chagas disease with no proven
      pathology. Efficacy will be measured through conversion from positive to negative
      parasitaemia according to the results of qualitative PCR tests from the end of treatment, and
      up to 12 months of follow-up from the beginning of treatment. Safety will be compared
      according to the frequency and severity of adverse events.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Proportion of patients with sustained negativation of parasitemia according to the results of qualitative PCR tests

Secondary Outcome

 Proportion of patients with negative parasitemia at 6 and 12 months follow-up form the beginning of treatment

Condition

Chagas Disease

Intervention

Short regimen of benznidazole

Study Arms / Comparison Groups

 Short regimen of benznidazole
Description:  Participants will receive an investigational treatment of benznidazole for 2 weeks.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

362

Start Date

July 28, 2021

Completion Date

February 2023

Primary Completion Date

February 2023

Eligibility Criteria

        Screening Criteria:

          -  Signed informed consent form.

          -  Between ≥18 and ≤60 years of age.

          -  Diagnosis of T. cruzi infection by conventional serology (a minimum of two positive
             tests).

          -  Ability to comply with all exams and specific protocol visits. Having a permanent
             address.

          -  Not presenting signs or symptoms of chronic cardiac and/or digestive forms of Chagas
             disease, defined according to national guidelines.

          -  No prior history of mental disorders or suicidal tendencies.

          -  Not suffering from acute or chronic illnesses that, in the Investigator's discretion,
             may interfere with the evaluation of the efficacy or safety of the investigational
             product (such as acute infections, a history of HIV infection, or liver or kidney
             diseases that have required treatment).

          -  Not having received a formal indication not to take BZN (contraindication, according
             to the Summary of Product Characteristics - SmPC). Contraindications to BZN basically
             include hypersensitivity to the active substance and its excipients. According to the
             SmPC for BZN, subjects will be advised not to drink alcoholic beverages during
             treatment.

          -  No prior history of hypersensitivity, allergy, or serious adverse reactions to any of
             the nitroimidazole compounds and/or its components.

          -  Have not previously undergone antiparasitic treatment for Chagas disease.

          -  No prior history of drug abuse or alcoholism.

          -  Not suffering from any disease that prevents subjects from consuming oral medication.

        Inclusion Criteria:

        After the screening period, subjects must meet ALL the inclusion criteria detailed below
        for recruitment:

        Confirmation of the diagnosis of T. cruzi infection by:

        Serial qualitative PCR (three samples collected on the same day, at least one of which must
        be positive)

        AND

        Conventional serology (a minimum of two tests must be reactive).

          -  Women of childbearing potential must have a negative pregnancy result at the time of
             inclusion, must not be breast-feeding, and must use a highly effective method of
             contraception until completion of the trial.

          -  Normal ECG (Heart rate: 50 -100 bpm; interval duration: PR ≤ 200 msec, QRS ≤120 msec,
             and QTc ≥ 350 msec and ≤ 450 msec) at screening.

          -  Normal echocardiogram (left ventricular diastolic diameter (LVDD) <= 55 mm, absence of
             Microaneurysm or tip aneurysm, Hypo or generalized akinesia, Systolic dysfunction (low
             fractional shortening and ejection fraction), and/or Mural thrombus).

          -  Normal chest X-ray (Cardiac silhouette with index <0.5).

        Exclusion Criteria:

        The presence of any of the items below will exclude subjects from inclusion in the study:

          -  Patient pregnant or intending to become pregnant during treatment and within 30 days
             of the last dose of study treatment.

          -  Signs or symptoms of the chronic cardiac and/or digestive form of Chagas disease,
             defined according to national guidelines.

          -  History of cardiomyopathy, heart failure, or ventricular arrhythmia.

          -  History of digestive surgery or mega syndromes.

          -  Acute or chronic disease that, in the Investigator's discretion, may interfere with
             the evaluation of the efficacy or safety of the investigational product (such as acute
             infection, history of HIV infection, or liver or kidney disease that has required
             treatment).

          -  Laboratory test values that are considered clinically significant or outside the
             allowable values, per CTCAE version 5.0 grade 1.

          -  Disease that prevents subjects from consuming oral medication.

          -  Subjects with a contraindication (known hypersensitivity) to any of the nitroimidazole
             compounds, e.g. metronidazole.

          -  Subjects with a history of allergy (serious or not), allergic rash, asthma,
             intolerance, sensitivity or photosensitivity to any drug.

          -  Concomitant use and/or consumption of allopurinol, antimicrobial and antiparasitic
             agents, herbal medicines, dietary supplements and energy drinks.

          -  Scheduled surgery that may interfere with the conduct of the trial and/or with the
             treatment evaluation.

          -  Inability to attend study visits, comply with treatment, and cooperate with study
             procedures.

          -  Previous participation in a trial for the evaluation of the treatment of Chagas
             disease.

          -  Simultaneous participation in another trial or within 3 months prior to screening for
             this trial (in accordance with national regulations).

          -  Serious medical or psychiatric illness that increases the risk associated with study
             participation or that interferes with the interpretation of study results
      

Gender

All

Ages

18 Years - 60 Years

Accepts Healthy Volunteers

No

Contacts

Sergio Sosa-Estani, MD, (54) 11 44898300, [email protected]

Location Countries

Argentina

Location Countries

Argentina

Administrative Informations


NCT ID

NCT04897516

Organization ID

NuestroBen


Responsible Party

Sponsor

Study Sponsor

Laboratorio Elea Phoenix S.A.

Collaborators

 Drugs for Neglected Diseases initiative

Study Sponsor

Sergio Sosa-Estani, MD, Study Director, Drugs for Neglected Diseases


Verification Date

September 2021