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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT03086226
• Date of registration: 25/01/2017
• Prospective Registration: Yes
• Primary sponsor: Drugs for Neglected Diseases
• Public title: Proof-of-Concept Superiority Trial of Fosravuconazole Versus Itraconazole for Eumycetoma in Sudan
• Scientific title: A Randomized, Double Blind Phase II Proof-of-Concept Superiority Trial of Fosravuconazole 200 mg or 300 mg Weekly Dose Versus Itraconazole 400 mg Daily, All Three Arms in Combination With Surgery, in Patients With Eumycetoma in Sudan
• Date of first enrolment: April 30, 2017
• Target sample size: 138
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03086226
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Sudan

Contacts

• Name: Nathalie Strub-Wourgaft, Dr

• Name: Ahmed H Fahal

• Name: Ahmed Fahal, Prof
• Affiliation: Mycetoma Research Centre, Soba University, Khartoum, Sudan

Key inclusion & exclusion criteria

4.1. Inclusion criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment
into the study:

1. Subjects with eumycetoma caused by Madurella mycetomatis confirmed by PCR.

2. Eumycetoma lesion = 2 cm and <10 cm in diameter

3. Single eumycetoma lesion present on the foot or lower limb

4. Age =18 years

5. Able to comply with protocol procedures and available for follow-up

6. Written informed consent from the subject

7. Female specific inclusion criteria

- Negative pregnancy test

- If female of child bearing potential, using adequate contraception for the period
of the trial to 2 months after completing study treatment 4.2. Exclusion criteria

The presence of any of the following will exclude a subject from study enrolment:

1. Previous surgical or medical treatment for eumycetoma which includes with 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 would preclude evaluation
of the eumycetoma.

3. Pregnancy or lactation at screening, intent to become pregnant

4. Concomitant or severe diseases that may compromise the subject follow-up or evaluation
(psychiatric condition, chronic hepatitis, neutropenia, or HIV/AIDS, diabetes
mellitus, adrenocortical insufficiency for example)

5. Contraindication to the use of itraconazole including congestive heart failure,
ventricular dysfunction, ventricular arrhythmia, negative inotropic state. For a
comprehensive list of contraindications and contraindicated concomitant medication
refer to the package insert for itraconazole (Sporanox®)

6. Contraindication to the use of fosravuconazole

7. Pre-existing liver disease, transaminase levels >2 x the laboratory's Upper Limit of
Normal (ULN), or elevated levels of alkaline phosphatase or bilirubin

8. Receiving or likely to require drugs that are either a substrate for CYP3A4 and/or
metabolized by CYP3A4 (cisapride, oral midazolam, nisoldipine, felodipine, pimozide,
quinidine, dofetilide, triazolam, methadone, and levacetylmethadol [levomethadyl] are
contraindicated)

9. Corrected QT by Fridericia's formula (QTcF) >450 msec on any ECG known about or taken
prior to entry

10. Subjects with Familial Short QT syndrome or (corrected QT interval) QTc prolongation

11. History of hypersensitivity to any azole antifungal drug.

12. Participation in other clinical trials within a six-month period.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Mycetoma

Intervention(s)

Drug: Itraconazole

Drug: Fosravuconazole

Primary Outcome(s)

Proportion of patients with complete cure at the End-of-Treatment [Time Frame: 12 months]

Secondary Outcome(s)

Propoprtion of patients with complete mycetoma cure by fungus genus at End of Treatment [Time Frame: 12 months]

Severity of the Adverse Events and Serious Adverse Events that lead to treatment discontinuation. [Time Frame: 15 months]

Time to complete cure [Time Frame: 15 months]

The proportion of subjects experiencing at least one Adverse Event [Time Frame: 15 months]

Propoprtion of patients with complete mycetoma cure by fungus genus at End of Study [Time Frame: 15 months]

Time to effective treatment [Time Frame: 15 months]

Proportion of patients considered to have effective treatment at the End of Treament [Time Frame: 12 months]

Time to failure [Time Frame: 15 months]

Immunological changes [Time Frame: 15 months]

Proportion of patients with complete cure of the Mycetoma at the end of the study [Time Frame: 15 months]

AUC at steady-state (AUCss) [Time Frame: 15 months]

CMax [Time Frame: 15 months]

Proportion of patients with mycological eradication of Mycetoma [Time Frame: 12 months]

Proportion of patients considered to have effective treatment at the End of Study [Time Frame: 12 months]

The frequency of the Adverse Events and Serious Adverse Events that lead to treatment discontinuation. [Time Frame: 15 months]

Secondary ID(s)

DNDi-FOSR-04-MYC

Source(s) of Monetary Support

Please refer to primary and secondary sponsors