Purpose / Objectives

Primary Outcome

• To evaluate the efficacy of SCY-078 (ibrexafungerp) as determined by a Data Review Committee at the primary endpoint.
• To evaluate safety of SCY-078 (ibrexafungerp)

Secondary Outcomes

• To evaluate the efficacy of ibrexafungerp as determined by the DRC at other time points.
• To evaluate the efficacy of ibrexafungerp as determined by the investigator.
• To determine the efficacy of ibrexafungerp by pathogen.
• To determine the efficacy of ibrexafungerp by disease category (type of fungal disease).
• To evaluate the efficacy of ibrexafungerp by  recurrence of the baseline fungal disease.
• To determine All-Cause Mortality.
• To evaulate the pharmacokinetics (PK) of ibrexafungerp by population PK analysis.

Diagnosis

• Infectious diseases in Hematology and Oncology: Fungal Infections

Subjects must have a documented invasive and/or severe fungal disease and meet all study criteria to be considered for enrollment.

Eligible fungal diseases are:

- Acute or chronicinvasive candidiasis (incl. candidemia)

- Akute or chronic invasive mucocutaneous candidiasis

- Disseminated/invasive dimorphic fungi

- Chronic pulmonary aspergillosis (CPA)

- Allergic bronchopulmonary aspergillosis (ABPA)

- Invasive pulmonary aspergillosis (IPA)

- Other emerging fungy including yeast and molds

Eligible subjects must also have documented evidence of failure of, intolerance to, or toxicity related to a currently approved SoC antifungal treatment.
Subjects will also be considered for enrollment if they have an eligible fungal disease and, in the judgement of the investigator, the subject cannot receive approved oral antifungal options (e.g. susceptibility of the organism or risk for drug-drug interactions) and a continued IV antifungal therapy is not desirable or feasible due to clinical or logistical circumstances.

Target population

Stage

invasive and/or severe, intolerance to standard treatment

Age

18-

Inclusion criteria

1. Be <18 years of age on the day the study informed consent form is signed

2. Documented eligible invasive and/or severe fungal disease (as defined in Table 1) that has been refractory to or intolerant of, or has toxicities associated with at least one SoC antifungal treatment, and/or in the judgement of the investigator, it is not feasible or desirable for the subject to receive continued IV antifungal therapy due to clinical or logistical circumstances and other oral antifungal alternatives are not appropriate.
3. Be able to tolerate medication orally or through a nasogastric or percutaneous endoscopic gastrostomy tube.
4. Subject and/or legal guardian must be able to understand and sign a written informed consent form (ICF), which must be obtained prior to treatment and any study-related procedures.
5.  Subject and/or legal guardian must be able to understand and sign a consent or authorization form which shall permit the use, disclosure and transfer of the subject’s personal health information. (e.g., in the U.S. HIPAA Authorization form).
6. Subject and/or legal Guardian must be able to understand and follow all study-related procedures including study drug administration.
7. Subject is not pregnant and is highly unlikely to become pregnant or to impregnate a partner.

Exclusion criteria

1. An invasive fungal disease with CNS involvement unless the subject is planned to receive combination therapy with ibrexafungerp and other antifungal.
2. There is inappropriate fungal infection source control e.g. persistent catheters, devices, identified abscess that is likely the source of the fungal infection.
3. Subject is hemodynamically unstable or and/or requiring vasopressor medication for blood pressure support.
4. Subject with abnormal liver test parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT) >10 x the upper limit of normal (ULN), and/or total bilirubin > 3 x ULN. Patients with unconjugated hyperbilirubinemia with diagnosis of Gilbert’s disease are not excluded.

5. Subject has a life expectancy < 30 days.
6. Any other condition or laboratory abnormality that, in the judgment of the
investigator, would put the subject at unacceptable risk for participation in the study or may interfere with the assessments included in the study.
7. Subject requires treatment with prohibited medications.
8. Subject with a known hypersensitivity to SCY-078, drug under study.
9. Subject is pregnant or lactating.
10. Subject has used an investigational drug within 30 days prior to the baseline visit.
11. Employees of SCYNEXIS, Inc., the investigator, or contract research organization (CRO) involved in the study, or an immediate family member (partner, offspring, parents, siblings, or sibling’s offspring) of an employee involved in the study.
12. Subject or legal representative is unable to provide written informed consent for any reason.
13. Subject is unlikely to comply with protocol requirements.

Study design

• Phase III
• Multicenter
• Prospective
• One-arm
• Open Label

Intervention

Eligible subjects will receive an initial loading dose of 750 mg BID (twice a day) of SCY-078 (3 tablets of 250 mg) during the first 2 days of treatment with subsequent doses of 750 mg orally QD (once a day) for up to 180 days, depending on fungal disease.

Miscellaneous

Treatment beyond 180 days may be permitted under certain circumstances to be agreed upon by the Investigator and the Sponsor on a per-subject basis. If subjects cannot swallow the whole tablet, the tablets may be split. In the event subjects experience gastrointestinal intolerance on the 750 mg QD dose, the tablets may be split and/or administered at 10 to 20-minute intervals. The daily dose may also be given as 375 mg (1 and ½ tablets) BID for subjects experiencing gastrointestinal intolerance.

Documents (password protected)

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Responsibilities in overall study

Sponsor

SCYNEXIS Inc.

Sponsor representative

Univ.-Prof. Dr. med. Oliver A. Cornely

• Tel. +49 221 478-85523
• Fax +49 221 478-1421445
• oliver.cornely@uk-koeln.de

(National) Coordinating Investigator

Univ.-Prof. Dr. med. Oliver A. Cornely

Project management

ZKS Köln

• leading
• Tel. +49 (0)221 478 88121
• Fax +49 (0)221 478 7983
• info@zks-koeln.de

Dr. Sabine Sadura
Dr. rer. nat. Sabine Schleicher

ZKS Köln - Projekt Management

• CPA

Beatrix Burmeister

Monitoring

Clinscience (prev. EXPERIOR S.L.)

• partial responsibilities

Victor Martinez

Radboud university medical center Nijmegen; Clinical Research Centre Nijmegen, CRCN

• partial responsibilities

Marianne Linkels

ZKS Köln

• leading
• Tel. +49 (0)221 478 88121
• Fax +49 (0)221 478 7983
• info@zks-koeln.de

M. Sc. Annika Brüggen (geb. Schröder)
M.Sc. Martin Paus