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

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

Tracking Information
First Submitted Date  ICMJE September 11, 2018
First Posted Date  ICMJE September 14, 2018
Last Update Posted Date September 25, 2020
Actual Study Start Date  ICMJE January 22, 2019
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Study to Evaluate the Safety and Efficacy of the Coadministration of Ibrexafungerp (SCY-078) With Voriconazole in Patients With Invasive Pulmonary Aspergillosis
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Invasive Pulmonary Aspergillosis
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 12, 2018)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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  ICMJE Belgium,   Germany,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03672292
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Scynexis, Inc.
Study Sponsor  ICMJE Scynexis, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Angulo, MD Scynexis, Inc.
PRS Account Scynexis, Inc.
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP