Proof-of-Concept Study of E1224 to Treat Adult Patients With Chagas Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01489228
• Date of registration: 24/11/2011
• Prospective Registration: No
• Primary sponsor: Drugs for Neglected Diseases
• Public title: Proof-of-Concept Study of E1224 to Treat Adult Patients With Chagas Disease
• Scientific title: Phase 2 Randomized, Multicenter, Placebo-controlled, Safety and Efficacy Study to Evaluate Three Oral E1224 Dosing Regimens and Benznidazole for the Treatment of Adult Patients With Chronic Indeterminate Chagas Disease
• Date of first enrolment: June 2011
• Target sample size: 230
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01489228
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Bolivia

Contacts

• Name: Faustino Torrico, PhD
• Affiliation: Universidad Mayor San Simón. Cochabamba, Bolivia.

• Name: Fabiana P Alves, PhD

• Name: Joaquim Gascón, PhD
• Affiliation: CRESIB - Centre de Recerca en Salut Internacional de Barcelona, Spain.

• Name: Isabela Ribeiro, MD
• Affiliation: Drugs for Neglected Diseases initiative

Key inclusion & exclusion criteria

Screening Criteria:

- Age >18 to < 50 years

- Weight > 40 kg

- Diagnosis of T. cruzi infection by conventional serology (a minimum of two out of
three positive tests [enzyme linked immunosorbent assay (ELISA), indirect
immunofluorescence (IIF), or hemagglutination inhibition (HAI)])

- Signed, written informed consent form

- No signs and/or symptoms of the chronic cardiac and/or digestive form of CD

- No acute or chronic health conditions that may interfere with the efficacy and/or
safety evaluation of the study drug

- No formal contraindication to BZN and E1224

- No known history of hypersensitivity, allergic, or serious adverse reactions to the
study drugs

- No history of CD treatment with BZN or NFX at any time in the past

- No history of systemic treatment with itraconazole, ketoconazole, posaconazole,
isavuconazole, or allopurinol in the past

Inclusion Criteria:

- Confirmed diagnosis of T. cruzi infection by serial qualitative PCR AND Conventional
serology

- Women in reproductive age must have a negative serum pregnancy test at screening,
must not be breastfeeding, and consistently use and/or have partner consistently use
an adequate contraceptive method

- Normal ECG at screening

Exclusion Criteria:

- Abnormal laboratory test values at screening for the following parameters: total
White Blood Cells (WBC) count, platelet count, alanine transaminase (ALT), aspartate
transaminase (AST), total bilirubin, or creatinine; or gamma-glutamyl transferase
(GGT)

- History of alcohol abuse or any other drug addiction (as specified in the Study
Manual of Operations)

- Any condition that prevents the patient from taking oral medication

- Any concomitant use of antimicrobial or antiparasitic agents



Age minimum: 18 Years
Age maximum: 50 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic Chagas Disease, Indeterminate

Intervention(s)

Drug: E1224

Drug: Placebo

Drug: Benznidazole

Primary Outcome(s)

Serial negative qualitative Polymerase Chain Reaction (PCR) results (3 negative PCR results from 3 samples to be collected over 7 days) as a measure of parasitological cure at end of treatment [Time Frame: Day 65 (end of treatment)]

Secondary Outcome(s)

Changes in the levels of biomarkers over time: brain natriuretic peptide, troponin T, selected prothrombotic factors, lytic antibodies, apolipoprotein A1 and multiplex serodiagnostic assay [Time Frame: Day 36 , 65 and at 4, 6 and 12 months follow-up]

Incidence of serological conversion to negative and changes in titers over time as measured by conventional and non-conventional serologies [Time Frame: Day 65 and at 4, 6 and 12 months after treatment]

Consistently negative serial qualitative PCR as a measure of sustained parasitological eradication [Time Frame: 4, 6 and 12 months follow-up]

Area under the plasma concentration versus time curve (AUC), Peak Plasma Concentration (Cmax), Minimum Plasma Concentration (Cmin), Clearance, Volume of Distribution , and Plasma Terminal Half-Life (t1/2) of ravuconazole and benznidazole [Time Frame: Day 0 (pre-dose), Day 1 (after 1st dose), Day 2, Day 3, steady-state phase (D8-D50), at the end of treatment (D65) and at the 4 months follow-up visit]

Incidence and severity of adverse events (clinical and laboratory) [Time Frame: Up to 12 months follow-up]

Qualitative PCR as a measure of parasite eradication [Time Frame: Day 8, 15, 36 , 65 and at 4, 6 and 12 months follow-up]

Incidence of Serious Adverse Events and/or adverse events leading to treatment discontinuation [Time Frame: Up to 12 months follow-up]

Quantitative PCR as a measure of change in parasite load over time [Time Frame: Day 8, 15, 36, 65 and at 4, 6 and 12 months follow-up]

Early and late predictors of sustainable response to treatments [Time Frame: Up to 12 months follow-up]

Correlation of pharmacokinetic parameters with parasitological response, changes in biomarkers and safety outcomes [Time Frame: Day 8, 15, 36, 65, and at 4, 6 months and 12 months follow-up]

Secondary ID(s)

DNDi-CH-E1224-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Eisai Co., Ltd.