Study to Evaluate Fexinidazole Dosing Regimens for the Treatment of Adult Patients With Chagas Disease

NCT02498782 | Unknown Phase 2 DMC

• 1 other identifier: DNDi-CH-FEXI-001
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief Summary

The hypothesis is to evaluate if the treatment with Fexinidazole will lead to a better sustained clearance of the parasites at 6 months of follow-up when in comparison to placebo in patients with chronic indeterminate CD.

Conditions

Chagas Disease; Trypanosomiasis, South American; South American Trypanosomiasis; Disease, Chagas

Keywords

Chagas Disease; Dosage forms; Regimens

Outcome Measures

Primary Outcomes (3)

• Parasitological cure rate (PCR)

  Parasitological cure rate as determined by serial negative qualitative PCR results (3 negative PCR results, from 3 samples to be collected in the same day) at end of treatment (8 weeks) and sustained parasitological clearance until 6 months follow-up.

  8 weeks and sustained until 6 months

• Adverse events

  Incidence and severity of adverse events (clinical, laboratory and EKG)

  7 months

• Serious Adverse events

  Incidence of Serious Adverse Events and/or adverse events leading to treatment discontinuation

  7 months

Secondary Outcomes (4)

• Parasite Clearance (qualitative PCR)

  weeks 2, 3, 4, 6, 10, and at 4 and 6 months follow-up

• Parasite load

  weeks 2, 3, 4, 6, 10 and 4 and 6 months

• Serological response

  week 10, 4 and 6 months

• Blood culture for parasite genotyping

  6 months

Other Outcomes (1)

• Plasma level concentrations

  D0 (pre-dose), at randomly selected time at day 1, post-dose, at steady-state phase (week 2-9), and at week 10

Study Arms (7)

Fexinidazole, 1800 mg, 2 weeks

ACTIVE COMPARATOR

1800mg (High Dose) 2 weeks (HD - 2 weeks) Group: Fexinidazole, 1800 mg QD for 2 weeks, followed by placebo to complete 8 weeks (total dose: 25,2 g)

Drug: Fexinidazole; Drug: Placebo

Fexinidazole, 1800 mg, 4 weeks

ACTIVE COMPARATOR

1800mg (High Dose) 4 weeks (HD - 4 weeks) Group: Fexinidazole, 1800 mg QD for 4 weeks, followed by placebo to complete 8 weeks (total dose: 50,4 g)

Drug: Fexinidazole; Drug: Placebo

Fexinidazole, 1800 mg, 8 weeks

ACTIVE COMPARATOR

1800mg (High Dose) 8 weeks (HD - 8 weeks) Group: Fexinidazole, 1800 mg QD, for 8 weeks (total dose: 100,8 g)

Drug: Fexinidazole

Fexinidazole, 1200 mg, 2 weeks

ACTIVE COMPARATOR

1200mg (Dose 2 weeks) 2 weeks (LD - 2 weeks) Group: Fexinidazole, 1200 mg QD for 2 weeks, followed by placebo to complete 8 weeks (total dose: 16,8 g)

Drug: Fexinidazole; Drug: Placebo

Fexinidazole, 1200 mg, 4 weeks

ACTIVE COMPARATOR

1200mg (Low Dose) 4 weeks (LD - 4 weeks) Group: Fexinidazole, 1200 mg QD for 4 weeks, followed by placebo to complete 8 weeks (total dose: 33,6 g)

Drug: Fexinidazole; Drug: Placebo

Fexinidazole, 1200 mg, 8 weeks

ACTIVE COMPARATOR

1200mg (Low Dose) 8 weeks (LD - 8 weeks) Group: Fexinidazole, 1200 mg QD for 8 weeks (total dose: 67,2 g)

Drug: Fexinidazole

Placebo

PLACEBO COMPARATOR

Placebo (8 weeks) Group: Fexinidazole matched placebo tablets QD for 8 weeks.

Drug: Placebo

Interventions

Fexinidazole DRUG

Also known as: 1Himidazole,1methyl2[4methylthio)phenoxymethyl] 5nitroimidazole

Fexinidazole, 1200 mg, 2 weeks; Fexinidazole, 1200 mg, 4 weeks; Fexinidazole, 1200 mg, 8 weeks; Fexinidazole, 1800 mg, 2 weeks; Fexinidazole, 1800 mg, 4 weeks; Fexinidazole, 1800 mg, 8 weeks

Placebo DRUG

Fexinidazole, 1200 mg, 2 weeks; Fexinidazole, 1200 mg, 4 weeks; Fexinidazole, 1800 mg, 2 weeks; Fexinidazole, 1800 mg, 4 weeks; Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Confirmed diagnosis of T. cruzi infection by Serial qualitative PCR (three samples collected over a single day, at least one of which must be positive) AND Conventional serology (a minimum of two out of three positive tests must be positive \[Conventional ELISA, Recombinant Elisa or IIF)
• Women in reproductive age must have a negative serum pregnancy test at screening, must not be breastfeeding, and consistently use a highly effective contraceptive method during the entire trial.
• Normal EKG (PR ≤200 msec, QRS ≤120 msec, and QTc ≥400msec and ≤450 msec interval durations) at screening

You may not qualify if:

• Signs and/or symptoms of chronic cardiac and/or digestive form of CD (as per Study Manual of Operations)
• History of cardiomyopathy, heart failure or ventricular arrhythmia
• Any other acute or chronic health conditions that, in the opinion of the PI, may interfere with the efficacy and/or safety evaluation of the study drug (such as acute infections, history of HIV infection, diabetes, liver and renal disease requiring medical treatment)
• Laboratory test values considered clinically significant or out of the allowable range at screening as follows:
• Total WBC must be within the normal range, with an acceptable margin of +/- 5% (3,800 - 10,500 / mm3).
• Platelets must be within the normal range up to 550,000 / mm3
• Total bilirubin must be within the normal range Transaminases (ALT and AST) must be within the normal range, with an acceptable margin of 25% above the upper limit of normality (ULN), \< 1.25 x ULN.
• Creatinine must be within an acceptable margin of 10% above the ULN, \<1.10 x ULN.
• Alkaline phosphatase must be within the normal range up to Grade 1 CTCAE (\< 2.5 x ULN)
• GGT must be within the normal range up to 2x ULN.
• Potassium, Magnesium, Calcium must be within the normal range
• 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.
• Patients with contra-indication (known hypersensitivity) to other nitroimidazoles, e.g. metronidazole.
• Any concomitant use of antimicrobial or anti-parasitic agents.

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (2)

Plataforma Atención Integral de Pacientes con Enfermedad de Chagas

Cochabamba, Bolivia

RECRUITING

Plataforma de Atención Integral de Pacientes con Enfermedad de Chagas

Tarija, Bolivia

RECRUITING

Related Publications (1)

• Torrico F, Gascon J, Ortiz L, Pinto J, Rojas G, Palacios A, Barreira F, Blum B, Schijman AG, Vaillant M, Strub-Wourgaft N, Pinazo MJ, Bilbe G, Ribeiro I. A Phase 2, Randomized, Multicenter, Placebo-Controlled, Proof-of-Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease. Clin Infect Dis. 2023 Feb 8;76(3):e1186-e1194. doi: 10.1093/cid/ciac579.

  PMID: 35925555 DERIVED

MeSH Terms

Conditions

Chagas Disease

Interventions

fexinidazole

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Study Officials

• Faustino Torrico, MD

  Plataforma de Antención Integral de Pacientes con Enfermedad de Chagas, Cochabamba, Bolivia

  PRINCIPAL INVESTIGATOR

• Joaquim Gascón, MD

  Centro de Salud Internacional, Hospital Clínico de Barcelona

  PRINCIPAL INVESTIGATOR

• Lourdes O Daza, MD

  Plataforma de Antención Integral de Pacientes con Enfermedad de Chagas, Tarija, Bolivia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Isabela Ribeiro, MD

CONTACT

+552125290400; iribeiro@dndi.org

Fabiana BS Rocha, MD

CONTACT

+552125290400; fbarreira@dndi.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2014
• First Posted: July 15, 2015
• Study Start: July 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: February 1, 2016
• Last Updated: July 15, 2015

Record last verified: 2015-07

Locations

BO (2)