Proof-of-Concept Superiority Trial of Fosravuconazole Versus Itraconazole for Eumycetoma in Sudan

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-09

Study Completion Date

2022-03-07

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study is a single-center, comparative, randomized, double-blind, parallel-group, active-controlled, clinical superiority trial of Fosravuconazole versus Itraconazole combined with surgery in subjects with eumycetoma in Sudan.

There will be three arms in this study: The first arm will be Fosravuconazole 300 mg weekly, the second arm will have Fosravuconazole 200 mg weekly and the control arm is the standard treatment using itraconazole 400mg daily.

At 3 months time-point, interim analysis will be done and one of the study arms will be dropped according to the drop-the-loser design, based on efficacy or toxicity.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

A Phase 3 Efficacy and Safety Study of Fosmanogepix for the Treatment of Adult Participants With Candidemia and/or Invasive Candidiasis.

NCT05421858

Candidemia Candidiasis, Invasive

RECRUITING PHASE3

Comparative Trial of Micafungin Versus Fluconazole for Treating Esophageal Candidiasis

NCT00666185

Candidiasis, Oral

COMPLETED PHASE3

Comparative Study of Micafungin (FK463) Versus Placebo as Prophylactic Antifungal Therapy in the ICU

NCT00048750

Invasive Fungal Infections

TERMINATED PHASE3

Efficacy and Safety of Micafungin for Injection in Prevention and Treatment of Fungal Infection in Hematological Tumors

NCT04738955

Hematological Tumors Patients With High Risk Factors of Invasive Fungal Disease

UNKNOWN PHASE4

Anti-mold Azole in the Prophylaxis for Invasive Fusariosis

NCT02714504

Fusariosis Onychomycosis

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Eumycetoma is a fungal disease caused by Madurella mycetomatis. The disease is chronic, granulomatous and inflammatory. It usually involves subcutaneous tissues and leads to masses and sinuses from which fungal grains are discharged. It is most probably introduced post trauma e.g. thorn prick. It is associated with major morbidity and can be disabling, disfiguring and highly stigmatizing. In advanced cases it may be fatal. Eumycetoma is most prevalent in what is known as mycetoma belt.

Current treatment modalities for eumycetoma are disappointing. The response is characterized by low cure rates, high amputation rates, high up drop out from follow up and high recurrence rates. The available drugs for the treatment of eumycetoma are expensive, potentially toxic and require a long treatment period up to 12 months. By that time the mass is well encapsulated and is removed surgically. Despite prolonged medical treatment, the causative organisms are commonly found to still be viable and can be cultured from the surgical specimen.

The objectives of this study are to determine the comparative efficacy, safety, and tolerability of Fosravuconazole versus itraconazole as first-line treatment for subjects with eumycetoma caused by Madurella mycetomatis. The primary end-point will be complete cure after 12 months treatment as evidenced by clinical assessment showing absence of mycetoma mass with closure of sinuses and absent discharge, normal ultrasonic examination of the lesion, or the presence of fibrosis only associated with a negative fungal culture from a surgical biopsy from the former mycetoma site. The secondary endpoints are the outcome at 3-month's time point based on the same criteria as 12 month and/or treatment-related adverse events at the 3- and 12-month visits. The study will also monitor plasma drug levels of ravuconazole and itraconazole that will be included in a logistic model with other clinical and laboratory parameters to predict outcome. In addition, immunological studies will be done to describe the developing or changing immune responses during treatment. Lastly, all strains collected will be cultured and typed and with assessment of antifungal resistance.

This study is a single-center, comparative, randomized, double-blind, parallel-group, active-controlled, clinical superiority trial in subjects with eumycetoma requiring surgery. There will be three arms this study: The first arm will have Fosravuconazole 300 mg weekly and the second arm will have Fosravuconazole 200 mg weekly. Both arms will be evaluated at 3 months. At this time-point, one of the study arms will be dropped according to the drop-the-loser design, based on efficacy or toxicity. The control arm is the standard treatment using itraconazole 400mg daily. Patients will receive treatment for one year. An interim analysis is planned after data has been accumulated for sample size of 28 for 3 months end point.

This study will be done at the Mycetoma Research Centre, Sudan when ethics and regulatory approvals are received. The study plans to recruit 138 subjects by the end of the trial. The main inclusion criteria are subjects who provide consent, aged 18 years or more with primary moderate eumycetoma (size 2-10 cm) caused by Polymerase Chain Reaction (PCR) confirmed Madurella mycetomatis. Females in the child bearing age will require stringent contraception. The main exclusion criteria are eumycetoma \> 10 cm, previous treatment, significant concomitant illness that preclude evaluation and treatments or conditions treated with drugs that are known to interact with the azoles.

The study is expected to new safer and more efficacious eumycetoma treatment.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Mycetoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Fosravuconazole 300 mg

Given throughout the study for 12 months as the experimental arm.

Both experimental arms will be evaluated at 3 months. At this time-point, one of the study arms will be dropped according to the drop-the-loser design, based on efficacy or toxicity.

Group Type EXPERIMENTAL

Fosravuconazole

Intervention Type DRUG

Fosravuconazole will be given in two arms either as 300mg or 200mg. The drop-the loser design adaptive clinical trial design will allow two stages of the trial separated by a data based decision. In the first stage a decision will be taken on which arm to drop either the Fosravuconazole 200 or the Fosravuconazole 300 arm. The best treatment will be compared against the standard of care, itraconazole. At the end the focus will be comparing the best treatment against standard of care.

Fosravuconazole 200 mg weekly

Given throughout the study for 12 months as the experimental arm.

Both experimental arms will be evaluated at 3 months. At this time-point, one of the study arms will be dropped according to the drop-the-loser design, based on efficacy or toxicity.

Group Type EXPERIMENTAL

Fosravuconazole

Intervention Type DRUG

Fosravuconazole will be given in two arms either as 300mg or 200mg. The drop-the loser design adaptive clinical trial design will allow two stages of the trial separated by a data based decision. In the first stage a decision will be taken on which arm to drop either the Fosravuconazole 200 or the Fosravuconazole 300 arm. The best treatment will be compared against the standard of care, itraconazole. At the end the focus will be comparing the best treatment against standard of care.

Itraconazole 400mg daily

Given throughout the study for 12 months as the comparator arm.

Group Type ACTIVE_COMPARATOR

Itraconazole

Intervention Type DRUG

This will be the active comparator

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Fosravuconazole

Fosravuconazole will be given in two arms either as 300mg or 200mg. The drop-the loser design adaptive clinical trial design will allow two stages of the trial separated by a data based decision. In the first stage a decision will be taken on which arm to drop either the Fosravuconazole 200 or the Fosravuconazole 300 arm. The best treatment will be compared against the standard of care, itraconazole. At the end the focus will be comparing the best treatment against standard of care.

Intervention Type DRUG

Itraconazole

This will be the active comparator

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

E1224 Sporanox

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Participants with eumycetoma caused by M. mycetomatis confirmed by PCR.
2. Participants with eumycetoma requiring surgery.
3. Eumycetoma lesion ≥ 2 cm and \< 16 cm in diameter. Note: A lesion was defined as either one single lesion on one anatomical area or multiple lesions on one anatomical area provided that the total affected area remained within the given limits.
4. Age ≥ 15 years.
5. Able to comply with protocol procedures and available for follow-up.
6. Written informed consent from the participant. If the participant was \< 18 years old, there had to be a signed consent from a parent or legal guardian AND a written assent signed by the participant.

1. Negative pregnancy test.
2. If women of childbearing potential (WOCBP), to use adequate contraception during the trial period until 2 months after completion of trial treatment.

Exclusion Criteria

1. Previous surgical or medical treatment for eumycetoma which included any previous antifungal treatment.
2. Presence of loco-regional lymphatic extension, osteomyelitis, other bone involvement based on radiology or any pre- or co-existing condition that could have precluded evaluation of the eumycetoma. Note: The presence of bone involvement would need a different treatment with a longer duration.
3. Pregnancy or lactation at screening, or intent to have become pregnant.
4. Concomitant or severe diseases that could have compromised the participant follow-up or evaluation (e.g., psychiatric condition, chronic hepatitis, neutropenia, human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), diabetes mellitus or adrenocortical insufficiency).
5. Severe malnutrition as defined by a body mass index (BMI) \< 16 kg/m2.
6. Contraindication to use itraconazole, including congestive heart failure, ventricular dysfunction, ventricular arrhythmia and negative inotropic state; Note: for a comprehensive list of contraindications and contraindicated concomitant medication refer to the package insert for itraconazole (Sporanox®);
7. Contraindication to the use of fosravuconazole;
8. Pre-existing liver disease, transaminase levels \> 2x the laboratory's upper limit of normal (ULN) or elevated levels of alkaline phosphatase (ALP) or bilirubin.
9. Was receiving or likely to have required drugs that were either a substrate for cytochrome P450 family 3 subfamily A member 4 (CYP3A4) and/or metabolised by CYP3A4 (cisapride, oral midazolam, nisoldipine, felodipine, pimozide, quinidine, dofetilide, triazolam, methodone and levacetylmethadol \[levomethadyl\] were contraindicated);
10. Fridericia's corrected QT interval (QTcF) \> 450 msec on any ECG known about or taken prior to trial entry.
11. Familial short QT syndrome or corrected QT interval (QTc) prolongation.
12. History of hypersensitivity to any azole antifungal drug.
13. Participation in other CTs within a 6-month period.

Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No