Clinical Trials Register

Summary
EudraCT Number:	2018-002565-18
Sponsor's Protocol Code Number:	SCY-078-206
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-06-03
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2018-002565-18

A.3

Full title of the trial

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 (SCYNERGIA)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A trial to evaluate the Safety and Efficacy of SCY-078 when co-administrated with Voriconazole to treat Patients with Invasive Aspergillosis.

A.3.2

Name or abbreviated title of the trial where available

SCYNERGIA

A.4.1

Sponsor's protocol code number

SCY-078-206

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03672292

A.5.4

Other Identifiers

Name:

US IND:

Number:

107,521

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	SCYNEXIS, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	SCYNEXIS, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SCYNEXIS, Inc.
B.5.2	Functional name of contact point	Philip Deane
B.5.3	Address:
B.5.3.1	Street Address	One Evertrust Plaza, 13th Floor
B.5.3.2	Town/ city	Jersey City
B.5.3.3	Post code	NJ 07302
B.5.3.4	Country	United States
B.5.4	Telephone number	0012016882241
B.5.5	Fax number	0012018845490
B.5.6	E-mail	philip.deane@scynexis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ibrexafungerp
D.3.2	Product code	SCY-078 citrate salt
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IBREXAFUNGERP
D.3.9.1	CAS number	1207753-03-4
D.3.9.2	Current sponsor code	SCY-078 citrate salt
D.3.9.3	Other descriptive name	MK-3118
D.3.9.4	EV Substance Code	SUB193372
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with Invasive Pulmonary Aspergillosis

E.1.1.1

Medical condition in easily understood language

Infection caused by Aspergillus, a common mold (a type of fungus)

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10059259
E.1.2	Term	Pulmonary aspergillosis
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of the coadministration of SCY-078 and voriconazole compared with the coadministration of SCY-078 placebo and voriconazole in the treatment of invasive pulmonary aspergillosis (IPA).

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of the coadministration of SCY-078 and voriconazole compared with that of SCY-078 placebo and voriconazole in the treatment of IPA
o based on Global Response
 as determined by the Data Review Committee (DRC)
 as determined by the Principal Investigator
o based on all-cause mortality (ACM)
o based on serum galactomannan index (GMI) decrease
o based on clinical response, mycological response and radiological response
 as determined by the DRC
 as determined by the Principal Investigator
• To evaluate the pharmacokinetics (PK) of SCY-078 and voriconazole

E.2.3

Trial contains a sub-study

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 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 one of the following:
a. a diagnosis of a hematological malignancy or a myelodysplastic syndrome or aplastic anemia or has undergone hematopoietic cell transplantation, OR
b. 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
c. 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
d. with inherited severe immunodeficiency (e.g. chronic granulomatous disease, severe combined immunodeficiency).
5. Subject has not received more than 4 days (96 hours) of prior mold-active antifungal 12 NOV 2018 CONFIDENTIAL Page 22
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.
6.For subjects who were receiving antifungal prophylaxis, the IPA episode would, in the investigator´s judgement, be adequately treated with voriconazole .
7. Subject is able to tolerate medication orally or through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube.
8. 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. A female subject who is not of reproductive potential is defined as one who: (1) has reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels in the postmenopausal range as determined by the local laboratory, or 12 months of spontaneous amenorrhea); (2) is 6 weeks´ post-surgical bilateral oophorectomy or hysterectomy; or (3) has undergone bilateral tubal ligation. Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (i.e., anorexia nervosa).
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 whom has undergone a successful vasectomy. A successful vasectomy is defined as (1) microscopic documentation of azoospermia, or (2) a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post vasectomy.
c. Subject is a male or female subject who is of reproductive potential, is not pregnant or nursing, and agrees to remain abstinent or use (or have his/her partner use) 2 acceptable methods of contraception starting from the time of consent through 28 days after the completion of study therapy. Acceptable methods of birth control are intrauterine device, condom and highly effective hormonal contraceptives.
Note: Participating females of childbearing potential must have a negative urine or serum pregnancy test (β-human chorionic gonadotropin [β-hCG]) at Screening and prior to enrollment (Baseline/Treatment Day 1) (performed by the site’s local laboratory).
9. Subject and/or legal representative is/are able to understand and sign a written ICF, which must be obtained prior to treatment and any study-related procedures.
10. Subject and/or legal representative 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 Information Portability and Accountability Act Authorization form).
11. Subject and/or legal representative is able to understand and follow all study-related procedures including study drug administration.
12. Subject is willing and able to comply with the study restrictions and participate for the full length of the study.

E.4

Principal 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 >10 x ULN and/or total bilirubin >5 x ULN.
Note: Subjects with unconjugated hyperbilirubinemia ( <7 mg/dL ) with a diagnosis of Gilbert’s disease are not excluded.
7. Subject has a grade II-IV acute or extensive chronic graft-versus-host disease (GvHD).
8. Subject has renal failure requiring dialysis.
9. Subject has a prolonged QTcF interval (Fridericia’s correction: QTc= QT/(RR)0.33) >480 ms for females and prolonged QTcF interval (Fridericia’s correction: QTc= QT/(RR)0.33) >450 ms for males, on the baseline ECG or other abnormalities deemed clinically significant by the investigator that would put the subject at unacceptable risk for participation in the study.
10. Subject has any other condition including history of conditions or medications that may increase the risk for QTc prolongation, 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.
11. Subject has a known hypersensitivity to SCY-078 and/or voriconazole or any of the components of the formulations.
12. Subject has participated in any other investigational study (except open-label studies including approved chemotherapy agents) within at least 28 days or 5.5 half-lives of the investigational product (whichever is longer) before signing the ICF.
13. Subject has received prior treatment with SCY-078 in a previous trial.
14. Subject is an employee of SCYNEXIS, Inc., the investigator or the Contract Research Organization (CRO) involved in the study, or is an immediate family member (partner, offspring, parent, sibling, or sibling’s offspring) of an employee involved in the study.
15. Subject is unlikely to comply with protocol requirements.

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the study

E.5.2

Secondary end point(s)

• Global Response as measured by:
o 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
• Overall survival, defined as the time from randomization to time of death up to Day 84
• Percentage of subjects who died (any cause) at Days 42 and 84
• Absolute reduction and percent change in serum GMI from Baseline to Weeks 1, 2, 4 and 6
• Percentage of subjects with the following changes in serum GMI from Baseline:
o Fifty percent reduction or greater at Weeks 1, 2, 4 and 6
o Twenty-five percent reduction or greater at Weeks 1, 2, 4 and 6
o Any percent reduction at Weeks 1, 2, 4 and 6
o Reduction equal to or greater than 0.25 at Weeks 1, 2, 4 and 6
o Reduction to < 0.5 at Weeks 1, 2, 4 and 6
• Time to achieve the following changes in serum GMI from Baseline:
o Fifty percent reduction
o Twenty-five percent reduction
o Any percent reduction
o Reduction equal to or greater than 0.25
o Reduction to < 0.5 in 2 consecutive samples
• Percentage of subjects with:
o Clinical Response at EoT, Day 42 and Day 84, as determined by the DRC
o Mycological Response at EoT, Day 42 and Day 84, as determined by the DRC
o Radiological Response at EoT, Day 42 and Day 84, as determined by the DRC
• Percentage of subjects with:
o Clinical Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator
o Mycological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator
o Radiological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator
• SCY-078 and voriconazole plasma concentrations population PK analysis

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoint is included in the relevant endpoint

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

tolerability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

United States

Belgium

Germany

E.8.7

Trial has a data monitoring committee

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

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

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subjects incapable of giving consent for reasons linked to their medical condition. Legal representative to provide consent on behalf of patients. Should the patient regain capacity informed consent will be obtained from them.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

none

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-10-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-06-26

P. End of Trial
P.	End of Trial Status	Completed

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