ICH GCP - EU Clinical trials Registry - 2022-000648-32 (IT)

Summary
EudraCT Number:	2022-000648-32
Sponsor's Protocol Code Number:	SCY-078-302
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-09-14
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

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	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	1 Evertrust Plaza, Floor 13
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	+12018845485
B.5.5	Fax number	+12018845490
B.5.6	E-mail	clinicaltrials@scynexis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Fluconazol-GRY® 200 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA GmbH (EU Marketing authorization 56728.03.00)
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Fluconazole
D.3.2	Product code	[N/A]
D.3.4	Pharmaceutical form	Capsule
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	FLUCONAZOLE
D.3.9.1	CAS number	86386-73-4
D.3.9.2	Current sponsor code	N/A
D.3.9.4	EV Substance Code	SUB07674MIG
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	200
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 2
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	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/0000064849
D.3 Description of the IMP
D.3.1	Product name	Ibrexafungerp
D.3.2	Product code	[N/A]
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	1965291-08-0
D.3.9.2	Current sponsor code	N/A
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
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

Invasive Candidiasis/ Candidemia

Candidiasi invasiva/Candidemia

E.1.1.1

Medical condition in easily understood language

Invasive Candidiasis/ Candidemia

Candidiasi invasiva/Candidemia

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	10064954
E.1.2	Term	Invasive candidiasis
E.1.2	System Organ Class	100000004862

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	10060573
E.1.2	Term	Candidemia
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 demonstrate that treatment of Invasive Candidiasis/ Candidemia with intravenous (IV) echinocandin followed by oral ibrexafungerp is non inferior to IV echinocandin followed by oral fluconazole based on 30-day all-cause mortality (ACM).

Dimostrare che il trattamento della candidiasi invasiva/candidemia con echinocandina endovenosa (e.v.) seguita da ibrexafungerp orale è non-inferiore a echinocandina e.v. seguita da fluconazolo orale in base alla mortalità per tutte le cause (ACM) a 30 giorni.

E.2.2

Secondary objectives of the trial

Key Secondary Objective:

• To demonstrate that treatment of Invasive Candidiasis/ Candidemia with IV echinocandin followed by oral ibrexafungerp is non-inferior to IV echinocandin followed by oral fluconazole based on Global Response (clinical, radiological, and mycological response, as confirmed by the Data Review Committee [DRC]) at Day 14.

Other Secondary Objectives:
• To compare the efficacy of the treatment regimens, based on:
- Global Response at Day 30 and End of Therapy (EOT) as determined by the PI and DRC,
- Clinical Response as determined by the PI and DRC,
- Mycological Response as determined by the DRC,
- no recurrence as determined by the DRC, and
- fungal-free survival as determined by the DRC.
• To evaluate the safety of the regimens.
• To evaluate the pharmacokinetics (PK) of ibrexafungerp.

Obiettivo secondario principale:
• Dimostrare che il trattamento della candidiasi invasiva/candidemia con echinocandina e.v. seguita da ibrexafungerp orale è non inferiore a echinocandina e.v. seguita da fluconazolo orale in base alla risposta globale (risposta clinica, radiologica e micologica confermata dal Comitato di revisione dei dati [DRC]) al Giorno 14.

Altri obiettivi secondari:
• Confrontare l’efficacia dei regimi di trattamento in base a:
- risposta globale determinata dallo sperimentatore principale (PI) e dal DRC al Giorno 30 e alla fine della terapia (EOT);
- risposta clinica determinata dal PI e dal DRC;
- risposta micologica determinata dal DRC;
- assenza di recidiva determinata dal DRC; e
- sopravvivenza libera da infezioni micotiche determinata dal DRC.
• Valutare la sicurezza dei regimi.
• Valutare la farmacocinetica (PK) di ibrexafungerp.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects must fulfill all of the following KEY criteria at Screening to be eligible for participating in the study:
1. Subject is a male or female adult > = 18 years of age on the day the study informed consent is signed.
2. Subject has a diagnosis of candidemia and/or invasive candidiasis, defined as evidence of Candida spp. in either a bloodstream or tissue culture from a normally sterile site (excluding eye, cardiac tissue, bone tissue, central nervous system or prosthetic device) collected < = 4 days (within 96 hours) prior to initiation of IV echinocandin accompanied by any related clinical sign and/or symptom (e.g., fever [on one occasion > 38°C], hypotension, or local signs of inflammation).

Per risultare idonei a partecipare allo studio, i soggetti dovranno soddisfare allo screening tutti i seguenti criteri PRINCIPALI:
1. Il soggetto è un adulto di sesso maschile o femminile di età > = 18 anni nel giorno della firma del consenso informato dello studio.
2. Il soggetto ha ricevuto una diagnosi di candidemia e/o candidiasi invasiva, intesa come evidenza di Candida spp. in un’emocoltura o coltura tissutale da sede normalmente sterile (escluso occhio, tessuto cardiaco, tessuto osseo, sistema nervoso centrale o protesi) effettuata < = 4 giorni (entro 96 ore) prima dell’inizio del trattamento con echinocandina e.v. accompagnata da segni e/o sintomi clinici correlati (ad es. febbre [in un’occasione > 38 °C], ipotensione o segni locali di infiammazione).

E.4

Principal exclusion criteria

A subject will be excluded from participation in the study if he or she meets any of the following KEY exclusion criteria:
1. Subject has any of the following forms of invasive candidiasis at Screening:
a. Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed),
b. Osteomyelitis,
c. Endocarditis or myocarditis,
d. Meningitis, endophthalmitis, or any central nervous system infection,
e. Chronic disseminated candidiasis,
f. Urinary tract candidiasis due to ascending Candida infection secondary to unresolved obstruction or non-removeable device in the urinary tract,
g. Patients with a sole diagnosis of mucocutaneous candidiasis, i.e., oropharyngeal, esophageal, or genital candidiasis; or Candida lower urinary tract infection or Candida isolated solely from respiratory tract specimens,
h. Patients with concurrent invasive fungal infection other than Candida spp., e.g., cryptococcosis, mold infection or endemic fungal infection,
i. Patients who failed a previous antifungal therapy for the same infection,
j. Subject has an inappropriately controlled fungal disease source (e.g., indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained) that is likely to be the source of the candidemia or invasive candidiasis.
2. Subject has abnormal liver test parameters: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 10-fold the upper limit of normal (ULN).
3. Subject has severe hepatic impairment and a history of chronic cirrhosis (Child-Pugh score > 9).
4. Subject has received more than 48 hours of non-echinocandin antifungal therapy for the treatment of invasive candidiasis (including candidemia) within 96 hours preceding initiation of IV echinocandin.
a. Exception: Receipt of antifungal therapy to which any Candida spp. isolated in qualifying culture is not susceptible.
5. Baseline QTcF > = 500 msec.

I soggetti saranno esclusi dalla partecipazione allo studio se soddisferanno uno qualsiasi dei seguenti criteri PRINCIPALI di esclusione:
1. Allo screening il soggetto presenta una qualsiasi delle seguenti forme di candidiasi invasiva:
a. artrite settica in protesi articolare (l’artrite settica in articolazione nativa è invece ammessa);
b. osteomielite;
c. endocardite o miocardite;
d. meningite, endoftalmite o qualsiasi infezione del sistema nervoso centrale;
e. candidiasi cronica disseminata;
f. candidiasi delle vie urinarie dovuta a infezione da Candida ascendente secondaria a ostruzione non risolta o dispositivo non rimovibile a livello delle vie urinarie;
g. pazienti con sola diagnosi di candidiasi mucocutanea, ossia candidiasi orofaringea, esofagea o genitale, oppure infezione da Candida alle basse vie urinarie o Candida isolata unicamente in campioni prelevati dalle vie respiratorie;
h. pazienti con infezione micotica invasiva concomitante diversa da Candida spp., ad es. criptococcosi, infezione da muffa o infezione micotica endemica;
i. pazienti andati incontro a fallimento con una precedente terapia antimicotica per la stessa infezione;
j. soggetti con fonte di malattia da fungo non adeguatamente controllata (ad es. catetere vascolare permanente o dispositivo non rimovibile oppure ascesso che non può essere drenato) che sia verosimilmente alla base della candidemia o della candidiasi invasiva.
2. Il soggetto presenta delle anomalie nei parametri dei test di funzionalità epatica: livelli di alanina aminotransferasi (ALT) o aspartato aminotransferasi (AST) > 10 volte il limite superiore della norma (ULN).
3. Il soggetto presenta una compromissione epatica severa e una storia di cirrosi cronica (punteggio Child-Pugh > 9).
4. Il soggetto è stato sottoposto a più di 48 ore di terapia antimicotica non a base di echinocandine per il trattamento di candidiasi invasiva (candidemia compresa) nelle 96 ore precedenti l’inizio del trattamento con echinocandina e.v.
a. Eccezione: somministrazione di una terapia antimicotica verso cui non risulta sensibile una qualsiasi delle specie di Candida isolate nella coltura ammissibile.
5. QTcF basale > = 500 msec.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study is ACM at Day 30 in the ITT population.

L’endpoint primario dello studio è la ACM al Giorno 30 nella popolazione intent-to-treat (ITT).

E.5.1.1

Timepoint(s) of evaluation of this end point

at Day 30

al Giorno 30

E.5.2

Secondary end point(s)

Key Secondary Endpoint:
The percentage of subjects with Successful Global Response, as determined by the DRC at Day 14.

Secondary Endpoints:
Efficacy Endpoints
• The percentage of subjects with Successful Global Response at Day 30 and EOT as determined by the PI and the DRC.
• The percentage of subjects with Successful Clinical Response at Day 14 and EOT as determined by the PI and the DRC.
• The percentage of subjects with Successful Mycological Response at Day 14 and EOT as determined by the DRC.
• The percentage of subjects with no recurrence before EOT and at 2 weeks and 6 weeks after EOT as determined by the DRC.
• The percentage of subjects alive with Successful Global Response and no recurrence at 6 weeks after EOT as determined by the DRC.
Safety Endpoints
• Frequency of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs, serious adverse events (SAEs), and safety laboratory assessments.
PK Endpoint
• Ibrexafungerp plasma concentrations.

Endpoint secondario principale:
Percentuale di soggetti con risposta globale di successo determinata dal DRC al Giorno 14.

Endpoint secondari:
Endpoint di efficacia
• Percentuale di soggetti con risposta globale di successo determinata dal PI e dal DRC al Giorno 30 e alla EOT.
• Percentuale di soggetti con risposta clinica di successo determinata dal PI e dal DRC al Giorno 14 e alla EOT.
• Percentuale di soggetti con risposta micologica di successo determinata DRC al Giorno 14 e alla EOT.
• Percentuale di soggetti con assenza di recidiva determinata dal DRC prima della EOT e a 2 e 6 settimane dopo la EOT.
• Percentuale di soggetti in vita con risposta globale di successo e assenza di recidiva determinate dal DRC a 6 settimane dopo la EOT.
Endpoint di sicurezza
• Frequenza di eventi avversi emergenti con il trattamento (TEAE), eventi avversi (AE) correlati al farmaco, interruzioni dovute ad AE, eventi Avversi gravi (SAE) e valutazioni di laboratorio di sicurezza.
Endpoint PK
• Concentrazioni plasmatiche di ibrexafungerp.

E.5.2.1

Timepoint(s) of evaluation of this end point

Key secondary endpoint at Day 14
Efficacy endpoint:
• At Day 30 and EOT
• Day 14 and EOT
• Day 14 and EOT
• At 2 weeks and 6 weeks after EOT
• At 6 weeks after EOT

Endpoint secondario chiave al giorno 14
Endpoint di efficacia:
• Al 30° giorno e all'EOT
• Giorno 14 e EOT
• Giorno 14 e EOT
• A 2 settimane e 6 settimane dopo l'EOT
• A 6 settimane dopo l'EOT

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

Yes

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

E.6.13

Others

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

Yes

E.8.2.3.1

Comparator description

Fluconazolo

Fluconazole

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

Information not present in EudraCT

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

Israel

Korea, Republic of

South Africa

United States

France

Bulgaria

Spain

Czechia

Germany

Greece

Italy

Belgium

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

End of all treatment, including IV and oral.

La fine di tutti i trattamenti, compresi quelli per via endovenosa e orale.

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

E.8.9.2

In all countries concerned by the trial days

Kliiniset tutkimukset Nct sivu

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot