Clinical Trials Register

Summary
EudraCT Number:	2020-004381-19
Sponsor's Protocol Code Number:	NBI-74788-CAH2006
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:	2021-08-30
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-004381-19

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Crinecerfont (NBI-74788) in Pediatric Subjects with Classic Congenital Adrenal Hyperplasia, Followed by Open-Label Treatment

Studio randomizzato, in doppio cieco, controllato con placebo, volto a valutare la sicurezza e l'efficacia di crinecerfont (NBI-74788) in soggetti pediatrici affetti da iperplasia surrenalica congenita classica, seguito da trattamento in aperto

A.3.1

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

Study to Evaluate the Safety and Efficacy of Crinecerfont in Pediatric Patients With Classic Congenital Adrenal Hyperplasia

Studio volto a valutare la sicurezza e l'efficacia di Crinecerfont in soggetti pediatrici con iperplasia surrenalica congenita classica

A.3.2

Name or abbreviated title of the trial where available

n/a

A.4.1

Sponsor's protocol code number

NBI-74788-CAH2006

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/104/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Neurocrine Biosciences, 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	Neurocrine Biosciences, 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	Accelsiors CRO and Consultancy Services Ltd.
B.5.2	Functional name of contact point	Regulatory Unit
B.5.3	Address:
B.5.3.1	Street Address	103 Haros Str.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1222
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+3612990091
B.5.5	Fax number	+3612990096
B.5.6	E-mail	regulatory@accelsiors.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	Crinecerfont
D.3.2	Product code	[NBI-74788]
D.3.4	Pharmaceutical form	Capsule, hard
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.3.9.1	CAS number	752253-39-7
D.3.9.2	Current sponsor code	NBI-74788
D.3.9.3	Other descriptive name	Crinecerfont is a novel non-peptide selective corticotropin releasing factor 1 (CRF1 ) receptor antagonist.
D.3.9.4	EV Substance Code	SUB197132
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	50
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	EU/3/19/2194
D.3 Description of the IMP
D.3.1	Product name	Crinecerfont
D.3.2	Product code	[NBI-74788]
D.3.4	Pharmaceutical form	Oral drops, solution
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use Other use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	752253-39-7
D.3.9.2	Current sponsor code	NBI-74788
D.3.9.3	Other descriptive name	Crinecerfont is a novel non-peptide selective corticotropin releasing factor 1 (CRF1 ) receptor antagonist.
D.3.9.4	EV Substance Code	SUB197132
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Capsule, hard
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	Oral drops, solution
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

Congenital adrenal hyperplasia (CAH) is a group of rare inherited endocrine disorders characterized by a deficiency of one of the enzymes needed to make specific hormones.

L'iperplasia surrenalica congenita (CAH) è un gruppo di malattie endocrine ereditarie rare caratterizzate da una carenza di uno degli enzimi necessari per produrre ormoni specifici.

E.1.1.1

Medical condition in easily understood language

Classic Congenital Adrenal Hyperplasia (CAH)

Iperplasia surrenale congenita classica (CAH)

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

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	10010323
E.1.2	Term	Congenital adrenal hyperplasia
E.1.2	System Organ Class	100000004850

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To evaluate the efficacy of crinecerfont, compared with placebo, in reducing adrenal steroid levels during a glucocorticoid-stable period.
• To evaluate the efficacy of crinecerfont, compared with placebo, in reducing daily glucocorticoid dosage while maintaining adrenal androgen control.
• To evaluate the effect of crinecerfont, compared with placebo, on clinical endpoints associated with supraphysiologic glucocorticoid dosing and androgen excess.
• To evaluate plasma concentrations of crinecerfont and metabolites.
• To assess the safety and tolerability of crinecerfont.

• Valutare l’efficacia di crinecerfont rispetto a placebo in termini di riduzione dei livelli di steroidi surrenalici durante un periodo stabile di assunzione di glucocorticoidi.
• Valutare l’efficacia di crinecerfont rispetto a placebo in termini di riduzione della dose giornaliera di glucocorticoidi, pur mantenendo il controllo della produzione di androgeni surrenalici.
• Valutare l’effetto di crinecerfont rispetto a placebo su endpoint clinici associati alla somministrazione di dosi sovrafisiologiche di glucocorticoidi e all’eccesso di androgeni.
• Valutare le concentrazioni plasmatiche di crinecerfont e dei suoi metaboliti
• Valutare la sicurezza e la tollerabilità di crinecerfont.

E.2.2

Secondary objectives of the trial

n/a

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Be willing and able to adhere to the study procedures, including all requirements at the study center and return for the follow-up visit.
- Be a female or male 2 to 17 years of age with a body weight of at least 10 kg.
- Have a medically confirmed diagnosis of classic CAH due to 21- hydroxylase deficiency.
- Be on a stable regimen of glucocorticoid treatment for CAH.
- Have elevated adrenal androgens.
- If treated with fludrocortisone, be on a stable regimen with plasma renin activity (PRA) indicating adequate replacement.

- Essere disposti e capaci di aderire alle procedure di studio, incluse le esigenze al centro e tornare per la visita di follow-up
- Essere femmine o maschi di età compresa tra 2 e 17 anni con un peso corporeo di almeno 10 kg.
- Presentare una diagnosi confermata a livello medico di CAH classica dovuta a deficit di 21-idrossilasi
- Essere in un regime di dosaggio di trattamento stabile di glucocorticoidi per la CAH
- Presentare alti livelli di androgeni surrenalici
- Se trattati con fludrocortisone, essere in un regime stabile con attività di renina plasmatica (PRA) che indica una sostituzione adeguata.

E.4

Principal exclusion criteria

- Have a diagnosis of any of the other forms of classic CAH.
- Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic daily therapy with oral glucocorticoids.
- Have a clinically significant unstable medical condition or chronic disease other than CAH
- Have a history of malignancy, unless successfully treated with curative intent and considered to be cured.
- Have a known history of clinically significant arrhythmia or abnormalities on screening ECG.
- Have a known hypersensitivity or allergy to any corticotropin-releasing hormone (CRH) receptor antagonist.
- Females who are pregnant or lactating.

- Avere una diagnosi di qualsiasi altra forma di CAH classica
- Presentare un’anamnesi di surrenectomia bilaterale, ipopituitarismo, o altra condizione che richiede una terapia quotidiana cronica con glucocorticoidi orali.
- Avere una condizione medica instabile clinicamente significativa o malattia cronica diversa dalla CAH
- Presentare un’anamnesi di neoplasia maligna, a meno che non sia trattata con successo con intento curativo e sia considerata curata.
- Presentare un’anamnesi nota di aritmia cardiaca clinicamente rilevante o anomalie evidenziate dall’ECG allo screening
- Presentare una ipersensibilità nota o allergia a qualsiasi antagonista del recettore dell’ormone di rilascio della corticotropina (CRH).
- Soggetti di sesso femminile in gravidanza o in allattamento.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in serum androstenedione at Week 4.

Cambiamento rispetto al basale dell’androstenedione sierico alla Settimana 4

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 4

Settimana 4

E.5.2

Secondary end point(s)

- Percent change from baseline in glucocorticoid dose at Week 28
- Change from baseline in serum 17-hydroxyprogesterone at Week 4

- Cambiamento percentuale rispetto al basale della dose dei glucocorticoidi alla Settimana 28
- Cambiamento rispetto al basale del 17-idrossiprogesterone sierico alla Settimana 4

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 4 and Week 28

Settimana 4, Settimana 28

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

Yes

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

Yes

E.8.1.7.1

Other trial design description

periodo in aperto

open-label period

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

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

Canada

United States

Belgium

France

Germany

Italy

Poland

Spain

Sweden

Greece

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-08-30.

Yes

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

Parent(s) or legal guardian(s) of pediatric subjects must provide written informed consent.

Children.

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)

Subjects will return to previous standard of care treatment.

I soggetti torneranno al trattamento standard precedente.

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

2021-09-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-10-13

P. End of Trial
P.	End of Trial Status	Ongoing

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