Clinical Trials Register

Summary
EudraCT Number:	2018-002230-20
Sponsor's Protocol Code Number:	CRN00808-03
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-22
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

2018-002230-20

A.3

Full title of the trial

An open label exploratory study to evaluate the safety, pharmacokinetics and efficacy of CRN00808 in patients with acromegaly treated with somatostatin analogue based treatment regimens (ACROBAT EDGE)

Titolo completo della sperimentazione: Studio esploratorio in aperto per valutare la sicurezza, la farmacocinetica e l'efficacia di CRN00808 in pazienti con acromegalia trattati con regimi di trattamento basati su analoghi di somatostatina (ACROBAT EDGE)

A.3.1

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

An exploratory Phase 2 study to evaluate the Safety and Efficacy of CRN00808 for the treatment of acromegaly

Uno studio esploratorio di fase 2 per valutare la sicurezza e l’efficacia di CRN00808 nel trattamento dell’Acromegalia

A.3.2

Name or abbreviated title of the trial where available

ACROBAT EDGE

A.4.1

Sponsor's protocol code number

CRN00808-03

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	Crinetics Pharmaceuticals, 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	Crinetics Pharmaceuticals, 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	50 Miskolci Str
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1147
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+3612990091
B.5.5	Fax number	+36112990096
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	CRN00808
D.3.2	Product code	[CRN00808]
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.3.9.2	Current sponsor code	CRN00808.HCl
D.3.9.3	Other descriptive name	CRN00808 is an oral non-peptide small molecule somatostatin receptor 2 (SST2) agonist
D.3.9.4	EV Substance Code	SUB194845
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	5
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CRN00808
D.3.2	Product code	[CRN00808]
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.3.9.2	Current sponsor code	CRN00808.HCl
D.3.9.3	Other descriptive name	CRN00808 - is an oral non-peptide small molecule somatostatin receptor 2 (SST2) agonist
D.3.9.4	EV Substance Code	SUB194845
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	10
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acromegaly

Acromegalia

E.1.1.1

Medical condition in easily understood language

Acromegaly is a chronic metabolic disorder in which there is too much
growth hormone and the body tissues gradually enlarge

l’Acromegalia è un disturbo metabolico cronico in cui si verifica troppo ormone della crescita e i tessuti del corpo si ingrandiscono gradualmente

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	PT
E.1.2	Classification code	10000599
E.1.2	Term	Acromegaly
E.1.2	System Organ Class	10014698 - Endocrine disorders

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

1.To evaluate the efficacy of CRN00808 in acromegaly subjects treated with somatostatin analogue based treatment regimens;
2.To evaluate the safety and tolerability of CRN00808 in acromegaly subjects;
3.To evaluate the pharmacokinetics (PK) of CRN00808 in acromegaly subjects.

1.Valutare l'efficacia di CRN00808 nei soggetti affetti da acromegalia, trattati con regimi di trattamento a base di analoghi della somatostatina;
2.Valutare la sicurezza e la tollerabilità di CRN00808 nei soggetti affetti da acromegalia;
3.Valutare la farmacocinetica (PK) di CRN00808 nei soggetti affetti da acromegalia.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male and female subjects 18 to 70 years of age
2.Confirmed diagnosis of acromegaly with either a partial or complete response to protocol defined somatostatin analogue therapy regimens
3.Females must be non-pregnant and non-lactating, and either surgically
sterile, post-menopausal, or using effective method(s) of birth control
4.Willing to provide signed informed consent

1.Soggetti maschili e femminili dai 18 ai 70 anni di età;
2.Confirmed diagnosis of acromegaly with either a partial or complete response to protocol defined somatostatin analogue therapy regimens
3.Le femmine non devono essere in gravidanza o in allattamento, e nemmeno sterilizzate chirurgicamente, in post menopausa o nel either surgically sterile, post-menopausal, o stiano utilizzando metodi effettivi di contraccezione;
4.Disponibilità a fornire un consenso informato firmato.

E.4

Principal exclusion criteria

1.Treatment naïve acromegaly subjects
2.Prior treatment with CRN00808
3.Pituitary surgery within 6 months prior to Screening or radiation
therapy at any time prior to the study entry;
4.History or presence of malignancy except adequately treated basal cell
and squamous cell carcinomas of the skin within the past 5 years.
5.Use of any investigational drug within the past 30 days or 5 half-lives,
whichever is longer
6.Positive test at Screening for HIV, hepatitis B surface antigen (HBsAg)or hepatitis C antibody (HCV-Ab) or has a history of a positive result
7.History of alcohol or substance abuse in the past 12 months
8.Any condition that in the opinion of the investigator would jeopardize
the subject's appropriate participation in this study
9.Cardiovascular conditions or mediations associated with prolonged QT
or those which predispose subjects to heart rhythm abnormalities.
10.Subjects with symptomatic cholelithiasis
11.Subjects with clinically significant abnormal findings during the
Screening Period, and any other medical condition(s) or laboratory
findings that, in the opinion of the Investigator, might jeopardize the
subject's safety or ability to complete the study
12.Subjects taking octreotide LAR at a dose higher than 40 mg, or lanreotide depot at a dose higher than 120 mg, or pasireotide LAR at a dose higher than 60 mg;
13.Subjects who usually take octreotide LAR or lanreotide depot less
frequently than every 4 weeks (e.g. every 6 weeks or 8 weeks);

1.Soggetti naïve al trattamento per l’Acromegalia.
2.Trattamenti precedenti con CRN00808.
3.Intervento chirurgico alla ghiandola pituitaria entro i 6 mesi precedenti allo Screening o radioterapia effettuata in qualsiasi momento precedente all’entrata nello studio;
4.Presenza o trascorsi di tumore maligno eccetto carcinoma cutaneo basocellulare squamoso adeguatamente trattato entro gli ultimi 5 anni.
5.Uso di qualsiasi farmaco sperimentale entro gli ultimi 30 giorni o 5 emivite, a seconda del quale abbia avuto più durata.
6.Test allo Screening positivi ad HIV, antigeni di superficie di Epatite B (HBsAg) o anticorpi di epatite C (HCV-Ab) o trascorsi di risultati positivi
7. Trascorsi di abuso di alcool o sostanze negli ultimi 12 mesi
8. Qualsiasi condizione che secondo lo sperimentatore potrebbe mettere a repentaglio l’appropriata partecipazione del soggetto in questo studio
9.Condizioni cardiovascolari o mediazioni associate a QT prolungato o soggetti predisposti ad aritmie cardiache.
10.Soggetti con colelitiasi sintomatica
11.Soggetti con significanti risultanze alterate durante il periodo di Screening e con qualsiasi altra condizione medica o di laboratorio che, secondo lo Sperimentatore, può compromettere la sicurezza del soggetto o l’abilità a completare lo studio.
12.Subjects taking octreotide LAR at a dose higher than 40 mg, or lanreotide depot at a dose higher than 120 mg, or pasireotide LAR at a dose higher than 60 mg;
13.Soggetti che solitamente assumono octreotide LAR o deposito di lanreotide meno frequentemente di ogni 4 settimane (ad esempio ogni 6 settimane o 8 settimane)

E.5 End points

E.5.1

Primary end point(s)

Change from baseline (mean of Screening values) in IGF-1 level at W13

L’endpoint primario è il cambiamento dalla baseline (media dei valori dello screening) nel livello di IGF-1 alla S13.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 13

Settimana 13

E.5.2

Secondary end point(s)

1.Proportion of subjects with the mean of their last two consecutive IGF-
1 measurements =ULN;
2.Proportion of subjects with the mean of their last two consecutive IGF-
1 measurements =1.5×ULN;
3.Proportion of subjects who achieve serum GH <5.0 ng/mL at W13.

1.Proporzione dei soggetti con la media delle ultime due misurazioni consecutive della IGF-1 =ULN;
2.Proporzione dei soggetti con la media delle ultime due misurazioni consecutive della IGF-1 =1,5×ULN;
3.Proporzione dei soggetti che raggiungono un livello di GH siero <5,0 ng/mL alla S13.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 13

Settimana 13

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

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

All subjects will receive IMP with actual dose blinded. Placebo will be used for dose blinding.

Tutti i soggetti riceveranno il farmaco di studio con dose attuale in cieco. Il Placebo sarà utilizz

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

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

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

Russian Federation

Serbia

United States

Germany

Greece

Hungary

Italy

Poland

Romania

Slovakia

United Kingdom

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

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

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

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 precedente trattamento standard

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

2019-07-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-11-07

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

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