Evaluate Safety and Efficacy of the Coadministration of Ibrexafungerp With Voriconazole in Patients With Invasive Pulmonary Aspergillosis (SCYNERGIA)

Scynexis

Status and phase: Terminated; Phase 2

Conditions: Invasive Pulmonary Aspergillosis

Treatments: Drug: SCY-078; Drug: Voriconazole; Other: Oral Placebo Tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT03672292

2018-002565-18 (EudraCT Number)

SCY-078-206

Details and patient eligibility

About

Study to evaluate the safety and efficacy of coadminstration of SCY-078 with a mold-active azole (voriconazole) compared to voriconazole in patients with invasive pulmonary aspergillosis.

Full description

This is a multicenter, randomized, double-blind, two-arm study to evaluate the safety, tolerability, efficacy and PK of the coadministration of SCY-078 plus voriconazole compared to those of voriconazole in male and female subjects 18 years of age and older with a probable or proven invasive pulmonary aspergillosis.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 probable or proven IPA based on the protocol-specified criteria (Section 22.3) that requires antifungal treatment. Note: Subjects with possible IPA may enter the screening phase of the study but will only be randomized after meeting criteria for probable or proven IPA.
3. Subject has a result of a serum GMI from a sample obtained within the 96 hours preceding enrollment into the study (Baseline/Treatment Day 1).
4. Subject has a diagnosis of a hematological malignancy or a myelodysplastic syndrome or aplastic anemia or has undergone hematopoietic cell transplantation OR
5. Subject who either recently resolved or ongoing neutropenia (neutropenia defined as absolute neutrophil count < 0.5 x 10⁹/L [< 500/mm³] for > 10 days), temporally related to the onset of fungal disease OR
6. Subject who received treatment with other recognized T-cell immunosuppressants (such as cyclosporine, tacrolimus, monoclonal antibodies or nucleoside analogs) during the past 90 days including solid organ transplant patients OR
7. Subject with inherited severe immunodeficiency (e.g. chronic granulomatous disease, severe combined immunodeficiency)
8. Subject has not received more than 4 days (96 hours) of prior mold-active antifungal therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study (Baseline/Treatment Day 1). However, subjects who have received more than 4 days but less than 7 days of prior mold-active antifungal therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study may be enrolled but will require approval from the study medical monitor, who will evaluate each subject on a case-by-case basis.
9. Subject has an IPA episode that, in the investigator´s judgement, requires antifungal therapy and may be adequately treated with voriconazole (i.e., the IPA is not a breakthrough infection while receiving a mold-active azole antifungal [voriconazole, posaconazole, isavuconazole or itraconazole] that requires therapy with a non-azole antifungal agent).

Exclusion criteria

1. Subject has a fungal disease with central nervous system involvement suspected at Screening.
2. Subject is receiving, has received or anticipates to be receiving concomitant medications that are listed in the prohibited medication list (Appendix A in full protocol) within the specified washout periods.
3. Subject has a Karnofsky score <20.
4. Subject is expected to die from a non-infectious cause within 30 days from the day the study ICF is signed.
5. Subject is under mechanical ventilation.
6. Subject has abnormal liver test parameters: AST or ALT >5 x ULN and/or total bilirubin >2.5 x ULN.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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22 participants in 2 patient groups, including a placebo group

SCY-078 plus Voriconazole

Experimental group

Description:

Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks

Treatment:

Drug: Voriconazole

Drug: SCY-078

Voriconazole mono-therapy

Placebo Comparator group

Description:

Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks

Treatment:

Other: Oral Placebo Tablets

Drug: Voriconazole