E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients > 18 years of age with a documented invasive and/or severe fungal disease that has been intolerant or refractory (rIFI) to Standard of Care (SoC) antifungal treatment. |
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E.1.1.1 | Medical condition in easily understood language |
severe fungal diseases who do not easily respond to, or who are intolerant to, the current treatment for their disease. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate the efficacy of ibrexafungerp in the treatment of severe fungal diseases by a Data Review Committee (DRC) at the primary timepoint. •To evaluate safety of ibrexafungerp. |
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E.2.2 | Secondary objectives of the trial |
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 (ACM) • To evaluate the pharmacokinetics (PK) of ibrexafungerp by population PK analysis • To evaluate the efficacy of ibrexafungerp as determined by other disease-specific endpoints |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is a male or female adult ≥18 years of age on the day the study informed consent form (ICF) is signed. 2. Subject has a documented eligible fungal disease that has been refractory to, has relapsed after, or the subject has intolerance to or demostrate toxicities resulting from an approved SOC antifungal treatment (as defined in protocol Table 5). The subject is also eligible if, in the judgement of the investigator, long-term IV antifungal therapy is not feasible or desirable due to clinical or logistical circumstances or if other oral antifungal alternatives are not appropriate. 3. Subject is able to tolerate medication orally or through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube. 4. Subject and/or legal guardian is/are able to understand and sign a written ICF, which must be obtained prior to treatment and any studyrelated procedures. 5. Subject and/or legal guardian is 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 US, a Health Insurance Portability and Accountability Act [HIPAA] authorization form). 6. Subject and/or legal guardian is 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 since he/she meets at least one of the following criteria: a. Subject is a female subject who is not of reproductive potential and is eligible without requiring the use of contraception. b. Subject is a male subject who is not of reproductive potential and is eligible without requiring the use of contraception. A male subject who is not of reproductive potential is defined as one who has undergone a successful vasectomy. c. Subject is a male or female subject who is of reproductive potential and agrees to remain abstinent if it is the subject's preferred method of contraception, or, if sexually active, use (or have their partner use) 2 acceptable methods of contraception starting from the time of consent through 28 days after the completion of study therapy. |
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E.4 | Principal exclusion criteria |
1. Subject has an invasive fungal disease with central nervous system involvement unless the subject is planned to receive combination therapy with ibrexafungerp and other antifungal 2. Subject has an inappropriately controlled fungal disease source (e.g., persistent catheters, devices, identified undrained abscess) that is likely to be the source of the fungal disease. 3.Subject is hemodynamically unstable and/or requiring vasopressor medication for blood pressure support. 4. Subject has abnormal liver test parameters: AST or ALT >10 x ULN and/or total bilirubin >5 x ULN. Note: Subjects with unconjugated hyperbilirubinemia with a diagnosis of Gilbert’s disease are not excluded. 5. Subject is unlikely to survive 30 days. 6. Subject has 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 the prohibited medications. 8. Subject has known hypersensitivity to ibrexafungerp. 9. Subject is pregnant or lactating. 10. Subject has received any other investigational drug (i.e., new chemical entity) within at least 30 days (or 5 and a half half-lives of the investigational product) before signing the ICF. 11. Subject is an employee of SCYNEXIS, Inc., the Investigator, or contract research organization 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/are unable to provide written informed consent for any reason. 13. Subject is unlikely to comply with protocol requirements. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Efficacy as measured by the percentage of subjects with Global Response at TOC (Day 17) for VVC and at EOT for all other diseases as determined by a DRC • Safety as measured by: physical examination, vital signs, AEs, and laboratory tests |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
TOC (Day 17) for VVC and at EOT (after up to 180 days of treatment) for all other diseases |
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E.5.2 | Secondary end point(s) |
• The percentage of subjects who achieve Global Response at additional time points as applicable for each disease (Table 16), as determined by the DRC and by the Investigator • The percentage of subjects who achieve Clinical Response by pathogen at time points applicable for each disease (Table 16), as determined by the DRC and the Investigator • The percentage of subjects who achieve Mycological Response by pathogen at time points applicable for each disease (Table 16), as determined by the DRC and the Investigator • The percentage of subjects who achieve Clinical Response by disease category (type of fungal disease) at time points applicable for each disease (Table 16), as determined by the DRC and the Investigator • The percentage of subjects who achieve Mycological Response by disease category (type of fungal disease) at time points applicable for each disease (Table 16), as determined by the DRC and the Investigator • The percentage of subjects with a recurrence of the baseline fungal disease at the 25-Day FU for VVC and at the 6-Week FU for all other diseases as determined by the DRC • ACM at Day 42 • Time to death from any cause • Describe ibrexafungerp plasma concentrations • Disease-specific secondary endpoints, as assessed by the DRC (See table 2 in study protocol) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Acute or chronic invasive candidiasis, including candidemia : EoT, Day 42, 6-Week FU Acute or chronic severe mucocutaneous candidiasis, including EC OPC, CMC: EOT, Day 42, Day 84, 6-Week FU Vulvovaginal candidiasis: Day 17, 25-Day FU [Day 32], 35-Day FU [Day 42]) Disseminated/invasive dimorphic fungi: EOT, Day 42, Day 84, 6-Week FU Chronic Pulmonary Aspergillosis: EOT, Day 90, Day 180, every 3 months while on Tx if beyond Day 180, 6-Week FU Allergic Bronchopulmonary Aspergillosis: EOT, Day 90, Day 180, every 3 months while on Tx if beyond Day 180, 6-Week FU Invasive Pulmonary Aspergillosis: EOT, Day 42, Day 84, 6-Week FU Other emerging fungi including yeasts and molds: EOT, Day 42, Day 84, 6-Week FU |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Germany |
Netherlands |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |