AzTrials
AzTrials

Chagas' Disease (Chronic) NosPhase 2FEXI12NCT03587766

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

A Phase 2 study testing Fexinidazole in people with Chagas' Disease (Chronic) Nos, run by Drugs for Neglected Diseases at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Chagas' Disease (Chronic) Nos
What is being tested?
Fexinidazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
45 participants
Where
1 siteSpain
Study dates
13 Nov 2017to 28 Aug 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Following the screening period, patients must also meet all of the following inclusion criteria to be eligible for randomization:
  • 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
  • 24 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)

Who cannot join

  • 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).
Show all 28Show fewer
  • 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
  • Electrolytes (Ca, Mg, K) must be within the normal range
  • Hepatitis screen must be negative for acute and/or chronic infection (Hepatitis A antibody, Imunoglobulina M (IgM); Hepatitis B surface Ag, Hepatitis B
  • 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, anti-parasitic agents, and/or of herbal medicines, food supplements and energetic drinks
  • Any concomitant medication with drug known risk of Torsade de Pointe, according AZCERT Scientific Publications and SADS Foundation (www.crediblemeds.org/index.php/new-drug-list)
  • Any planned surgery likely to interfere with the trial conduction and/or treatment evaluation
  • Unlikely to return for study visits, comply with study treatment and co-operate with the trial-related procedures.
  • Any previous participation in any clinical trial for Chagas Disease treatment evaluation
  • Participation in another trial at the same time or within 3 months prior to selection (according to local regulations).

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Hospital Clinic

    Barcelona, Catalunia, 08036

Other trials in Spain

About this study

Official title: Phase 2 Randomized, Multicenter, Double-blinded Safety and Efficacy Study to Evaluate Oral Fexinidazole Dosing Regimens for the Treatment of Adult Patients With Chronic Indeterminate Chagas Disease

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).

Read the detailed description

Fexi anti-protozoal activity against T. cruzi has been demonstrated by various in vitro and in vivo studies.

Patients will be randomly assigned to receive one of three different treatment regimen arms containing either the active drug or matching placebo tablet

Following conclusion of 12 months of follow-up of DNDi-CH-FEXI-001 clinical trial, unblinded data review showed high sustained parasite clearance rates of FEXI even at the lowest dose tested (1200 mg 2 weeks), including in patients that received < 3days treatment.

Being tested
Fexinidazole, Placebo Oral Tablet
Keywords
Trypanosoma cruzi Infection, Chagas' Disease, Trypanosomiasis, South American, American Trypanosomiasis, Kissing bug
Medical subject headings
Chagas Disease, Bronchiolitis Obliterans Syndrome, Pyloric Stenosis, Hypertrophic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FexinidazoleDrug

    Also called FEXI

    Drug: fexinidazole (FEXI)

  • Placebo Oral TabletDrug

    Also called Placebo

    Drug: fexinidazole

Study groups in NCT03587766
Study groupRoleWhat they receive
Group AExperimentalFexinidazole (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).
Receives: Drug: Fexinidazole; Drug: Placebo Oral Tablet
Group BExperimentalFexinidazole (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).
Receives: Drug: Fexinidazole; Drug: Placebo Oral Tablet
Group CExperimentalFexinidazole (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).
Receives: Drug: Fexinidazole; Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence and severity of adverse events.

    Measured: 12 months

Secondary outcomes (2)

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

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

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2018
  2. Study start13 Nov 2017
  3. Primary completion19 Dec 2018
  4. Study completion28 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03587766
Sponsor's protocol ID
DNDi-FEX-12-CH
Other IDs
2016-004905-15, 2016
Acronym
FEXI12
Status last verified
Sep 2020
First submitted
27 Apr 2018
Last updated
23 Sep 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Not yet decided how Individual Participant Data (IPD) will be shared, This action is under internal review within DNDi.

Publications

  • WHO | Chagas disease (American trypanosomiasis) [Internet]. WHO. [cited 2013 Aug 22]. Available from: http://www.who.int/mediacentre/factsheets/fs340/en/index.html

  • Bern C, Montgomery SP. An estimate of the burden of Chagas disease in the United States. Clin Infect Dis. 2009 Sep 1;49(5):e52-4. doi: 10.1086/605091.

    PubMed 19640226

  • Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazue G, Bray MA, Pecoul B. Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e923. doi: 10.1371/journal.pntd.0000923.

    PubMed 21200426

  • Raether W, Seidenath H. The activity of fexinidazole (HOE 239) against experimental infections with Trypanosoma cruzi, trichomonads and Entamoeba histolytica. Ann Trop Med Parasitol. 1983 Feb;77(1):13-26. doi: 10.1080/00034983.1983.11811668.

    PubMed 6411009

  • Moraes CB, Giardini MA, Kim H, Franco CH, Araujo-Junior AM, Schenkman S, Chatelain E, Freitas-Junior LH. Nitroheterocyclic compounds are more efficacious than CYP51 inhibitors against Trypanosoma cruzi: implications for Chagas disease drug discovery and development. Sci Rep. 2014 Apr 16;4:4703. doi: 10.1038/srep04703.

    PubMed 24736467

  • Bahia MT, de Andrade IM, Martins TA, do Nascimento AF, Diniz Lde F, Caldas IS, Talvani A, Trunz BB, Torreele E, Ribeiro I. Fexinidazole: a potential new drug candidate for Chagas disease. PLoS Negl Trop Dis. 2012;6(11):e1870. doi: 10.1371/journal.pntd.0001870. Epub 2012 Nov 1.

    PubMed 23133682

  • Caldas S, Caldas IS, Cecilio AB, Diniz LF, Talvani A, Ribeiro I, Bahia MT. Therapeutic responses to different anti-Trypanosoma cruzi drugs in experimental infection by benznidazole-resistant parasite stock. Parasitology. 2014 Oct;141(12):1628-1637. doi: 10.1017/S0031182014000882.

    PubMed 25045804

  • Munoz J, Gomez i Prat J, Gallego M, Gimeno F, Trevino B, Lopez-Chejade P, Ribera O, Molina L, Sanz S, Pinazo MJ, Riera C, Posada EJ, Sanz G, Portus M, Gascon J. Clinical profile of Trypanosoma cruzi infection in a non-endemic setting: immigration and Chagas disease in Barcelona (Spain). Acta Trop. 2009 Jul;111(1):51-5. doi: 10.1016/j.actatropica.2009.02.005. Epub 2009 Mar 5.

    PubMed 19426663

  • Rodriques Coura J, de Castro SL. A critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz. 2002 Jan;97(1):3-24. doi: 10.1590/s0074-02762002000100001.

    PubMed 11992141

  • Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet. 2010 Apr 17;375(9723):1388-402. doi: 10.1016/S0140-6736(10)60061-X.

    PubMed 20399979

  • Pinto Dias JC. The treatment of Chagas disease (South American trypanosomiasis). Ann Intern Med. 2006 May 16;144(10):772-4. doi: 10.7326/0003-4819-144-10-200605160-00012. No abstract available.

    PubMed 16702594

  • Castro AM, Luquetti AO, Rassi A, Rassi GG, Chiari E, Galvao LM. Blood culture and polymerase chain reaction for the diagnosis of the chronic phase of human infection with Trypanosoma cruzi. Parasitol Res. 2002 Oct;88(10):894-900. doi: 10.1007/s00436-002-0679-3. Epub 2002 Jun 15.

    PubMed 12209329

  • de Castro AM, Luquetti AO, Rassi A, Chiari E, Galvao LM. Detection of parasitemia profiles by blood culture after treatment of human chronic Trypanosoma cruzi infection. Parasitol Res. 2006 Sep;99(4):379-83. doi: 10.1007/s00436-006-0172-5. Epub 2006 Mar 29.

    PubMed 16570199

  • Britto C, Cardoso MA, Vanni CM, Hasslocher-Moreno A, Xavier SS, Oelemann W, Santoro A, Pirmez C, Morel CM, Wincker P. Polymerase chain reaction detection of Trypanosoma cruzi in human blood samples as a tool for diagnosis and treatment evaluation. Parasitology. 1995 Apr;110 ( Pt 3):241-7. doi: 10.1017/s0031182000080823.

    PubMed 7724232

  • Solari A, Ortiz S, Soto A, Arancibia C, Campillay R, Contreras M, Salinas P, Rojas A, Schenone H. Treatment of Trypanosoma cruzi-infected children with nifurtimox: a 3 year follow-up by PCR. J Antimicrob Chemother. 2001 Oct;48(4):515-9. doi: 10.1093/jac/48.4.515.

    PubMed 11581230

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fexinidazole in people with Chagas' Disease (Chronic) Nos, run by Drugs for Neglected Diseases at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events. (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03587766, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in