Study to Evaluate the Safety and Efficacy of the Coadministration of Ibrexafungerp (SCY-078) With Voriconazole in Patients With Invasive Pulmonary Aspergillosis (SCYNERGIA)

• ClinicalTrials.gov Identifier: NCT03672292
• Recruitment Status: Recruiting
• First Posted: September 14, 2018
• Last Update Posted: September 25, 2020
• Sponsor: Scynexis, Inc.
• Information provided by (Responsible Party): Scynexis, Inc.

Tracking Information

• First Submitted Date: September 11, 2018
• First Posted Date: September 14, 2018
• Last Update Posted Date: September 25, 2020
• Actual Study Start Date: January 22, 2019
• Estimated Primary Completion Date: May 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 12, 2018)

Adverse events; discontinuation due to AE; death [ Time Frame: through study completion, an average of 19 weeks ]

Frequency of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 13, 2018)

• Composite clinical, radiological and mycological response (global response) [ Time Frame: At end of treatment, day 42 and day 84 ]
  Percentage of subjects with Complete Response or Partial Response
• Death [ Time Frame: At Day 42 and Day 84 ]
  Percentage of subjects who died (any cause)
• Change in serum GMI [ Time Frame: Weeks 1, 2, 4 and 6 ]
  Absolute and percent change in serum GMI from Baseline
• Study drug and comparator plasma concentrations [ Time Frame: Through the first 2 weeks of study ]
  SCY-078 and voriconazole plasma concentrations population PK analysis

Original Secondary Outcome Measures (submitted: September 12, 2018)

• Global Response [ Time Frame: at maximum 13 weeks; at 6 weeks and 12 weeks ]
  Percentage of subjects with Complete Response or Partial Response at EoT (key secondary endpoint), Day 42 and Day 84, as determined by the DRC o Percentage of subjects with Complete Response or Partial Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator
• Death [ Time Frame: at 6 weeks and 12 weeks ]
  Percentage of subjects who died (any cause) at Days 42 and 84
• Changes in serum GMI from baseline [ Time Frame: At 1 week, 2 weeks, 4 weeks and 7 weeks ]
  Percentage of subjects with the following changes in serum GMI from Baseline:

  • Fifty percent reduction or greater at Weeks 1, 2, 4 and 6
  • Twenty-five percent reduction or greater at Weeks 1, 2, 4 and 6
  • Any percent reduction at Weeks 1, 2, 4 and 6
  • Reduction equal to or greater than 0.25 at Weeks 1, 2, 4 and 6
  • Reduction to < 0.5 at Weeks 1, 2, 4 and 6
• Clinical, mycological. radiological response evaluation by DRC [ Time Frame: at 6 weeks and 12 weeks ]
  Percentage of subjects with:

  • Clinical Response at Days 42 and 84, as determined by the DRC
  • Mycological Response at Days 42 and 84, as determined by the DRC
  • Radiological Response at Days 42 and 84, as determined by the DRC
• Clinical, mycological. radiological response evaluation by PI [ Time Frame: at 6 weeks and 12 weeks ]
  Clinical Response at Days 42 and 84, as determined by the Principal Investigator

  • Mycological Response at Days 42 and 84, as determined by the Principal Investigator
  • Radiological Response at Days 42 and 84, as determined by the Principal Investigator
• Study drug and comparator plasma concentrations [ Time Frame: through study completion, an average of 19 weeks ]
  SCY-078 and voriconazole plasma concentrations population PK analysis
• Time to achieve the changes in serum GMI from Baseline [ Time Frame: through study completion, an average of 19 weeks ]
  Fifty percent reduction

  • Twenty-five percent reduction
  • Any percent reduction
  • Reduction equal to or greater than 0.25
  • Reduction to < 0.5 in 2 consecutive samples

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety and Efficacy of the Coadministration of Ibrexafungerp (SCY-078) With Voriconazole in Patients With Invasive Pulmonary Aspergillosis
• Official Title: A Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of the Coadministration of SCY-078 With Voriconazole in Patients With Invasive Pulmonary Aspergillosis
• Brief Summary: 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.
• Detailed 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 hematological malignancy (HM) or a myelodysplastic syndrome or aplastic anemia or hematopoietic cell transplantation (HCT) and a probable or proven invasive pulmonary aspergillosis based on EORTCMSG criteria. In addition, all subjects must be positive (≥0.5) for serum GMI.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Invasive Pulmonary Aspergillosis

Intervention

• Drug: SCY-078
  Oral tablets of SCY-078
  Other Name: Ibrexafungerp
• Drug: Voriconazole
  Voriconazole IV vials or oral tablets
• Other: Oral Placebo Tablets
  Oral Placebo Tablets matching SCY-078
  Other Name: SCY-078 matching Placebo

Study Arms

• Experimental: SCY-078 plus Voriconazole

  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

  Interventions:

  • Drug: SCY-078
  • Drug: Voriconazole
• Placebo Comparator: Voriconazole mono-therapy

  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

  Interventions:

  • Drug: Voriconazole
  • Other: Oral Placebo Tablets

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 12, 2018): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2021
• Estimated Primary Completion Date: May 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 EORTC-MSG criteria.
3. Subject has a result of a serum GMI ≥0.5 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Nkechi Azie, MD; 201 688-2243 ext 2243; nkechi.azie@scynexis.com

Contact: Mihaela Tufa, MD; 201 884-5899 ext 5899; mihaela.tufa@scynexis.com

• Listed Location Countries: Belgium, Germany, Spain, United States

Administrative Information

• NCT Number: NCT03672292
• Other Study ID Numbers: SCY-078-206; 2018-002565-18 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Scynexis, Inc.
• Study Sponsor: Scynexis, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: David Angulo, MD; Scynexis, Inc.

• PRS Account: Scynexis, Inc.
• Verification Date: September 2020