A Study of the Use of Oral Posaconazole (POS) in the Treatment of Asymptomatic Chronic Chagas Disease (P05267) (STOP CHAGAS)

Phase 2 Proof-of-Activity Study of Oral Posaconazole in the Treatment of Asymptomatic Chronic Chagas Disease (Phase 2, Protocol No. P05267)

This is a study to compare the efficacy of oral posaconazole to placebo for the treatment of asymptomatic Chagas disease. The primary hypothesis of the study is that posaconazole 400 mg twice daily improves therapeutic response compared to placebo in participants with a diagnosis of asymptomatic chronic Chagas disease.

Study Overview

• Status: Completed
• Conditions: Chagas Disease
• Intervention / Treatment: Drug: Posaconazole; Drug: Placebo for posaconazole; Drug: Benznidazole

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Must have a positive serology result for Trypanosoma cruzi on any 2 of 3 of the following tests: indirect immunofluorescence, indirect hemagglutination, or enzyme-linked immunoabsorbent assay (ELISA)

• Must have a positive qualitative polymerase chain reaction (PCR) for Trypanosoma cruzi
• Must have a normal 12-lead electrocardiogram (ECG)
• Must have a normal 2-D echocardiogram
• Must have no evidence of ventricular tachycardia on 24-hour Holter monitoring
• Female participants of childbearing age must be using a medically accepted method of birth control before beginning study drug treatment and must agree to continue its use during the study, or must have been surgically sterilized
• Female participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at Screening and a negative urine pregnancy test at Baseline or within 72 hours before the start of study drug

Exclusion Criteria:

• Are breastfeeding, pregnant, or planning to become pregnant
• Body weight <60 kg
• Have an immunodeficiency or are immunosuppressed
• History of megacolon with obstipation or megaesophagus with severe swallowing impairment.
• Have previously received treatment with benznidazole or nifurtimox
• Known allergy/sensitivity to azoles
• Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal at Screening
• Has serum creatinine >2.5 mg/dL or 200 micromoles at Screening
• Has a history of severe alcohol abuse within two years from Screening
• Is taking any of the prohibited medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Posaconazole; Posaconazole (POS) 400 mg (10 mL) oral suspension twice daily for 60 days	Drug: Posaconazole; POS 40 mg/mL oral suspension; Other Names: SCH 056592, MK-5592
Placebo Comparator: Placebo; Posaconazole placebo (10 mL) oral suspension twice daily for 60 days	Drug: Placebo for posaconazole; Placebo oral suspension
Experimental: Posaconazole + Benznidazole; Posaconazole 400 mg (10 mL) oral suspension twice daily for 60 days and benznidazole (BNZ) 100 mg oral tablet twice daily (200-mg daily dose) for 60 days	Drug: Posaconazole; POS 40 mg/mL oral suspension; Other Names: SCH 056592, MK-5592; Drug: Benznidazole; BNZ 100 mg oral tablet
Active Comparator: Benznidazole + Placebo; Posaconazole placebo (10 mL) oral suspension twice daily for 60 days and benznidazole 100 mg oral tablet twice daily (200-mg daily dose) for 60 days	Drug: Placebo for posaconazole; Placebo oral suspension; Drug: Benznidazole; BNZ 100 mg oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Successful Response as Measured by Qualitative Polymerase Chain Reaction	Blood samples were collected for qualitative polymerase chain reaction (PCR) assay for Trypanosoma cruzi deoxyribonucleic acid (DNA). Successful response was defined as a negative qualitative PCR value at the Day 180 follow up visit.	Day 180

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Morillo CA, Waskin H, Sosa-Estani S, Del Carmen Bangher M, Cuneo C, Milesi R, Mallagray M, Apt W, Beloscar J, Gascon J, Molina I, Echeverria LE, Colombo H, Perez-Molina JA, Wyss F, Meeks B, Bonilla LR, Gao P, Wei B, McCarthy M, Yusuf S; STOP-CHAGAS Investigators. Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial. J Am Coll Cardiol. 2017 Feb 28;69(8):939-947. doi: 10.1016/j.jacc.2016.12.023.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2011
• Primary Completion (Actual): July 22, 2014
• Study Completion (Actual): January 12, 2015

Study Registration Dates

• First Submitted: May 13, 2011
• First Submitted That Met QC Criteria: June 20, 2011
• First Posted (Estimate): June 21, 2011

Study Record Updates

• Last Update Posted (Actual): August 27, 2018
• Last Update Submitted That Met QC Criteria: July 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Trypanosomiasis; Euglenozoa Infections; Chagas Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole; Benzonidazole
• Other Study ID Numbers: P05267; MK-5592-055 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis