Chagas disease (CD) is a disease caused by Trypanosoma cruzi, ranking among the world’s most neglected diseases. There is significant associated morbidity and mortality, particularly in chronic phase with target organ involvement. In Latin America, 21 countries are endemic for CD with an estimated 70 million people at risk. Spain has an estimated 46,000 people infected. The current treatment for CD has significant limitations and new therapeutic options are urgently needed.
Conditions
Interventions
Product Name: Fexinidazole
Pharmaceutical Form: Tablet
INN or Proposed INN: FEXINIDAZOLE
CAS Number: 59729-37-2
Concentration unit: mg m
Sponsors
Drugs for Neglected Diseases initiative (DNDi)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 and/or IIF) 2. 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. 3. Normal ECG (Heart rate: 50-100bpm; PR =200 msec, QRS 3 ventricular beats with >100bpm); Sustained Accelerated Idio-Ventricular rhythm (defined as >30 seconds duration and HR: 50bpm=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • 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 or family history of mental disability, suicidal tendencies or any other neuropsychiatric disorders, including previous treatment for anxiety or depression. • 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: o Total WBC must be within the normal range, with an acceptable margin of +/- 5% (3,800 – 10,500 / mm3). o Platelets must be within the normal range up to 550,000/mm3 o Total bilirubin must be within the normal range o 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. o Creatinine must be within an acceptable margin of 10% above the ULN, <1.10 x ULN. o Alkaline phosphatase must be within the normal range up to Grade 1 CTCAE (<,2.5 x ULN) o GGT must be within the normal range up to 2x ULN. o Fasting glucose (minimum of 8 hours from latest meal) must be within the normal range o Electrolytes (Ca, Mg, K) must be within the normal range o Hepatitis screen must be negative for acute and/or chronic infection (Hepatitis A antibody, IgM; Hepatitis B surface Ag, Hepatitis B core antibody, IgM/IgG, anti-HBs; Hepatitis C antibody) If the results of the blood tests (hematology and biochemistry) are out of the ranges defined above, but within the limits of CTCAE (version 4.03) Grade 1, and this laboratory finding is considered as non-clinically significant, a new sample can be collected for a retest. Only one retest will be allowed within the screening period. If the result of the retest is within the margins defined above, the Investigator will review the parameter(s) together with all other medical information available (medical history, clinical examinations, vital signs, etc.) and upon his/her medical judgement will decide if the patient is eligible or not for trial randomization. • Any condition that prevents the patient from taking oral medication. • Patients with any contra-indication (known hypersensitivity) to any nitroimidazoles, e.g. metronidazole • Patients with history of allergy (serious or not), allergic skin rash, asthma, intolerance, sensitivity or photosensitivity to any drug • Any concomitant use of allopurinol, antimicrobial, or anti-parasitic agents and/or of herbal medicines, food supplements and ene
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of alternative dosing regimens of orally administered FEXI in individuals with chronic indeterminate CD, by determining the proportion of patients who convert from positive to negative in serial, qualitative PCR test results (3 negative PCR results) at end of treatment (EOT) and sustain parasitological clearance at 4 months of follow-up, in comparison to historical placebo control.; Secondary Objective: • To measure the reduction in parasite load at weeks 1 (D1, D2, D3), 2, 3, 4, 6, 10, 12 and at 4, 6 and 12-months follow-up, as measured by quantitative PCR. • To assess the time to parasite DNA clearance (below the quantitative PCR Limit of Detection [LOD]) for each of the regimens • To explore the sustained parasitological response at week 12, and 4, 6 and 12 months for each of the regimens, in comparison with BZN historical control. • To assess the time to sustained clearance of parasitemia for each of the treatment regimens. • To determine the efficacy of the different dosing regimens in individuals with chronic indeterminate CD, by determining the proportion of patients who convert from positive to negative in serial, qualitative PCR test results (3 negative PCR results) at EOT, in comparison with historical placebo control. [...] ;Timepoint(s) of evaluation of this end point: Sustained parasitological response will be determined from EOT until 4-months follow-up (with evaluations at weeks 1 (D1, D2, D3), 2, 3, 4, 6, 10, 12, and at 4 months).; Primary end point(s): • Parasitological response as determined by serial negative qualitative PCR results (3 negative PCR results, from 3 samples to be collected in the same day) at EOT and sustained parasitological clearance until 4-months follow-up. For efficacy assessments, the EOT of each treatment arm will be defined in accordance to the duration of the | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: • Parasitological endpoints will be assessed on weeks 1 (D1, D2, D3), 2, 3, 4, 6, 10, 12, and at 4, 6 and 12-months follow-up. • Serological endpoints will be assessed baseline and at 12 months, in the case of conventional serology; and at week 12, and 4, 6 and 12-months of follow up (changes in titters over time) in the case of non-conventional serology. ; Secondary end point(s): • Parasite reduction ratio at D, D2 and -D3. • Parasite clearance at weeks 1 (D1, D2, D3), 2, 3, 4, 6, 10, 12, and at 4, 6 and 12-months follow-up as measured by qualitative PCR. • Change in parasite load over time assessed at weeks 1 (D1, D2, D3), 2, 3, 4, 6, 10, 12, and at 4, 6 and 12-months follow-up as measured by quantitative PCR. • Serological response by conventional serology assessed at 12 months of follow up and non-conventional serology assessed at week 12, and 4, 6 and 12-months of follow up (changes in titters over time) | — |
Countries
Spain
Contacts
Public ContactIrene Mínguez Ardura
Leon Research S.L.
Outcome results
None listed