Oral Fexinidazole Dosing Regimens for the Treatment of Adults With Chronic Indeterminate Chagas Disease

NCT03587766 | Completed Phase 2 DMC

• 2 other identifiers: DNDi-FEX-12-CH2016-004905-15
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This study focuses on the evaluation of low doses (600 and 1200 mg) and short treatment duration (at 3, 7 and 10 days) of fexinidazole (Fexi) to determine the minimal efficacious and safe dose for the treatment of adult patients with chronic indeterminate Chagas Disease (CD).

Conditions

Chagas' Disease (Chronic) Nos

Keywords

Trypanosoma cruzi Infection; Chagas' Disease; Trypanosomiasis, South American; American Trypanosomiasis; Kissing bug

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of adverse events.

  12 months

Secondary Outcomes (2)

• Pharmacokinetic : measure of blood concentration of fexinidazole, fexinidazole sulfoxide and fexinidazole sulfone in order to determine AUC0-t values, for all dose levels.

  D0 (pre-dose), Day 1, Day 2, Day 3, and at steady-state phase (week 2-10).

• Pharmacokinetic : measure of blood concentration of fexinidazole, fexinidazole sulfoxide and fexinidazole sulfone in order to determine Cmax values, for all dose levels.

  D0 (pre-dose), Day 1, Day 2, Day 3, and at steady-state phase (week 2-10).

Study Arms (3)

Group A

EXPERIMENTAL

Fexinidazole (FEXI) 600 mg x 10 days in a single daily dose orally (1 fexinidazole 600 mg tablet and 1 fexinidazole matching placebo oral tablet administered in a single daily dose) (total dose: 6.0 g).

Drug: Fexinidazole; Drug: Placebo Oral Tablet

Group B

EXPERIMENTAL

Fexinidazole (FEXI) 1200 mg x 3 days orally (2 fexinidazole 600 mg tablets administered in a single daily dose for 3 days), to be followed by matching placebo oral tablet for 7 days (2 fexinidazole matching placebo oral tablets administered once daily for 7 days) (total dose: 3.6 g).

Drug: Fexinidazole; Drug: Placebo Oral Tablet

Group C

EXPERIMENTAL

Fexinidazole (FEXI) 600 mg for 3 days, followed by 1200 mg in a single daily dose orally for 4 days (1 fexinidazole 600 mg tablet AND 1 fexinidazole matching placebo oral tablet administered in a single daily dose for 3 days, to be followed by 2 fexinidazole 600 mg tablets for 4 days), then followed by matching placebo oral tablet for 3 days (2 fexinidazole matching placebo tablets administered once daily for 3 days) (total dose: 6.6 g).

Drug: Fexinidazole; Drug: Placebo Oral Tablet

Interventions

Fexinidazole DRUG

Drug: fexinidazole (FEXI)

Also known as: FEXI

Group A; Group B; Group C

Placebo Oral Tablet DRUG

Drug: fexinidazole

Also known as: Placebo

Group A; Group B; Group C

Eligibility Criteria

• Age: 18 Years - 60 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 positive tests must be positive, Conventional ELISA, Recombinant Elisa, Chemiluminescence immunoassays and/or IIF)
• Women in reproductive age must have a negative serum pregnancy test at screening, must not be breastfeeding, must consistently use a highly effective contraceptive method until end of treatment and estimated FEXI, M1 and M2 clearance (total of 21 days). After this, contraception is no longer required.
• Normal ECG (Heart rate: 50-100bpm; PR interval ≤200 msec, QRS complex ≤120 msec, and QT interval corrected for heart rate (QTc) ≥350msec and ≤450 msec interval durations) at screening
• hour Holter-monitoring with no clinically relevant arrythmias (defined as Ventricular Tachycardia (defined as \>3 ventricular beats with \>100bpm); Sustained Accelerated Idio-Ventricular rhythm (defined as \>30 seconds duration and Heart Rate (HR): 50bpm\<HR\<100bpm); frequent Ventricular Premature Beats (10/hour); Atrial Fibrillation/flutter; Mobitz type 2 second degree AV block; High degree and complete AV block; Bradycardia episodes \<40bpm)

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.
• History of digestive surgery or mega syndromes.
• Personal history of mental disability or suicidal tendencies
• Hospital Anxiety and Depression Scale (HADS - Appendix 1) self-assessment score \>11 in each of the sub-scales. (Note: If HADS score \>11, retesting would be allowed before after a minimum period of 15 days and referral to counseling/evaluation.)
• 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 trial drug (such as acute infections, history of HIV infection, diabetes, uncontrolled systolic/diastolic blood pressure, liver, and renal diseases requiring medical treatment).
• Laboratory test values considered clinically significant or out of the allowable range at selection period as follows:
• Total White Blood Count (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)
• Gamma-glutamyl Transpeptidase (GGT) must be within the normal range up to 2x ULN.
• Fasting glucose (minimum of 8 hours from latest meal) must be within the normal range

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (1)

Hospital Clinic

Barcelona, Catalunia, 08036, Spain

Location

Related Publications (22)

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MeSH Terms

Conditions

Chagas Disease; Bronchiolitis Obliterans Syndrome; Pyloric Stenosis, Hypertrophic

Interventions

fexinidazole

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Joaquim Gascón, MD

  Centro de Salud Internacional, Hospital Clínico de Barcelona ISGlobal - Barcelona Institute for Global Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: As the study is double-blinded, the patient, investigators, pharmacist(s) and DNDi study team members involved with the clinical trial implementation will remain blinded to treatment allocation for the duration of the clinical trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is designed as a double-blind, randomized, prospective, comparative, pharmacokinetic-pharmacodynamic, and proof-of-concept trial design, with three-parallel groups and historical placebo control in patients with chronic indeterminate Chagas Disease.

Study Record Dates

• First Submitted: April 27, 2018
• First Posted: July 16, 2018
• Study Start: November 13, 2017
• Primary Completion: December 19, 2018
• Study Completion: August 28, 2019
• Last Updated: September 23, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

ES (1)