Clinical Trials Register

Summary
EudraCT Number:	2018-002565-18
Sponsor's Protocol Code Number:	SCY-078-206
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-06-11
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

Spain - AEMPS

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 Combination Therapy of SCY-078 with Voriconazole in Patients with Invasive Pulmonary Aspergillosis (SCYNERGIA)

Estudio multicéntrico, aleatorizado y doble ciego para evaluar la seguridad y la eficacia de la politerapia de SCY-078 con voriconazol en pacientes con aspergilosis pulmonar invasiva (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 used in combination with Voriconazole to treat Patients with Invasive Aspergillosis.

Un ensayo para evaluar la seguridad y la eficacia de SCY-078 cuando se usa en combinación con voriconazol para tratar pacientes con aspergilosis invasive.

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	Arpana Mirza
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	0012018845485
B.5.5	Fax number	0012018845490
B.5.6	E-mail	info@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

Pacientes con aspergilosis pulmonar invasiva

E.1.1.1

Medical condition in easily understood language

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

Infección causada por Aspergillus, un moho común (un tipo de hongo)

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 (“combination therapy”) compared with that of voriconazole monotherapy in the treatment of invasive pulmonary aspergillosis (IPA).

Evaluar la seguridad y la tolerabilidad de la administración conjunta de SCY-078 y voriconazol (“tratamiento combinado”) en comparación con la monoterapia con voriconazol en el tratamiento de la aspergilosis pulmonar invasiva (API).

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of the combination therapy compared with that of voriconazole monotherapy 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

• Evaluar la eficacia del tratamiento combinado en comparación con la monoterapia con voriconazol en el tratamiento de la API
o en base a la respuesta global
▪ según determine el Comité de Revisión de los Datos (CRD)
▪ según determine el investigador principal
o en base a la mortalidad por cualquier causa (MCC)
o en base al descenso del índice de galactomanano en suero (IGM)
o en base a la respuesta clínica, la respuesta micológica y la respuesta radiológica
▪ según determine el CRD
▪ según determine el investigador principal
• Evaluar la farmacocinética (FC) de SCY-078 y voriconazol

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 possible, 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.
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. 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).

1. El sujeto es un hombre o mujer adulto de ≥18 años el día en que se firme el formulario de consentimiento informado (FCI) del estudio.
2. El sujeto tiene una API posible, probable o probada según los criterios de EORTC-MSG.
3. El sujeto tiene un resultado de una prueba de IGM en suero ≥0,5 con una muestra obtenida en las 96 horas previas a la inscripción en el estudio (inicio/día de tratamiento 1).
4. El sujeto tiene un diagnóstico de neoplasia maligna hematológica o un síndrome mielodisplásico o una anemia aplásica o se ha sometido a un trasplante de hemocitoblastos.
5. El sujeto no ha recibido más de 4 días (96 horas) de tratamiento antifúngico activo contra hongos previo para el tratamiento del episodio de API en los 7 días previos a la inclusión en el estudio (inicio/día de tratamiento 1). Sin embargo, los sujetos que hayan recibido más de 4 días, pero menos de 7 días, de tratamiento antifúngico activo contra hongos previo para el tratamiento del episodio de API en los 7 días previos a la inscripción en el estudio, pueden ser inscritos, pero necesitarán la aprobación del supervisor médico del estudio, que evaluará a cada sujeto caso por caso.
6. El sujeto tiene un episodio de API que, según el criterio del investigador, necesita tratamiento antifúngico y puede tratarse adecuadamente con voriconazol (es decir, la API no es una infección recurrente mientras recibe un antifúngico azol activo contra hongos [voriconazol, posaconazol, isavuconazol o itraconazol] que requiere tratamiento con un agente antifúngico no azol).

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.
7. Note: Subjects with unconjugated hyperbilirubinemia with a diagnosis of Gilbert’s disease are not excluded.

1. El sujeto tiene una enfermedad fúngica con sospecha de afectación del sistema nervioso central en la selección.
2. El sujeto está recibiendo, ha recibido o tiene previsto recibir medicamentos concomitantes incluidos en la lista de medicamentos prohibidos (Anexo A del protocolo completo) dentro de los períodos de reposo farmacológico especificados.
3. El sujeto tiene una puntuación de Karnofsky <20.
4. Se espera que el sujeto fallezca por una causa no infecciosa en los 30 días siguientes al día en que se firma el FCI.
5. El sujeto tiene ventilación mecánica.
6. El sujeto tiene parámetros de pruebas hepáticas anómalos: AST o ALT >10 x LSN y/o bilirrubina total >5 x LSN.
7. Nota: No se excluye a los sujetos con hiperbilirrubinemia no conjugada con un diagnóstico de enfermedad de Gilbert.

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.

Frecuencia de los acontecimientos adversos durante el tratamiento (AADT), acontecimientos adversos (AA) relacionados con el medicamento, interrupciones debido a AA y muertes

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the study

A lo largo del estudio

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

• Respuesta global medida mediante:
o El porcentaje de sujetos con respuesta completa o respuesta parcial en FdT (criterio de valoración secundario clave), el día 42 y el día 84, según determine el CRD
o El porcentaje de sujetos con respuesta completa o respuesta parcial en FdT, el día 42 y el día 84, según determine el investigador principal
• La supervivencia global, definida como el tiempo transcurrido desde la aleatorización al fallecimiento hasta el día 84
• El porcentaje de sujetos que murieron (por cualquier causa) los días 42 y 84
• La reducción absoluta y el porcentaje de cambio en el IGM en suero desde el inicio hasta las semanas 1, 2, 4 y 6
• El porcentaje de sujetos con los siguientes cambios en el IGM en suero desde el inicio:
o Reducción del cincuenta por ciento o más en las semanas 1, 2, 4 y 6
o Reducción del veinticinco por ciento o más en las semanas 1, 2, 4 y 6
o Reducción en cualquier porcentaje en las semanas 1, 2, 4 y 6
o Reducción igual o mayor a 0,25 en las semanas 1, 2, 4 y 6
o Reducción < 0,5 en las semanas 1, 2, 4 y 6
• El tiempo para lograr los siguientes cambios en el IGM en suero desde el inicio:
o Reducción del cincuenta por ciento
o Reducción del veinticinco por ciento
o Reducción en cualquier porcentaje
o Reducción igual o mayor a 0,25
o Reducción < 0,5 en 2 muestras consecutives
• El porcentaje de sujetos con:
o Respuesta clínica en el FdT, el día 42 y el día 84, según determine el CRD
o Respuesta micológica en el FdT, el día 42 y el día 84, según determine el CRD
o Respuesta radiológica en el FdT, el día 42 y el día 84, según determine el CRD
• El porcentaje de sujetos con:
o Respuesta clínica en el FdT, el día 42 y el día 84, según determine el investigador principal
o Respuesta micológica en el FdT, el día 42 y el día 84, según determine el investigador principal
o Respuesta radiológica en el FdT, el día 42 y el día 84, según determine el investigador principal
• El análisis FC poblacional de las concentraciones en plasma de SCY-078 y voriconazol

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoint is included in the relevant endpoint

El punto clave de tiempo se incluye en criterio de valoación principal

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

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

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

Belgium

Germany

Spain

United States

E.8.7

Trial has a data monitoring committee

Yes

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

Última visita del útimo paciente

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.

Sujetos incapaces de dar su consentimiento por motivos relacionados con su condición médica. Representante legal dará su consentimiento en su nombre. En caso de que el paciente recupere su capacidad, se obtendrá de ellos un consentimiento informado.

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

2019-08-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-08-01

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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