Clinical trial • Phase III • Endocrinology|Rare Disease

CRINECERFONT for Classic congenital adrenal hyperplasia

Phase III trial of CRINECERFONT for Classic congenital adrenal hyperplasia.

Overview

Trial Therapeutic Area
Endocrinology|Rare Disease
Trial Disease
Classic congenital adrenal hyperplasia
Trial Stage
Phase III
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
07-06-2024
First CTIS Authorization Date
11-07-2024

Trial design

Randomised, open-label, placebo (crinecerfont placebo for oral capsules) as comparator arm; active arm: crinecerfont (nbi-74788) 100 mg twice daily (bid).-controlled Phase III trial across 31 sites in Austria, Belgium, Bulgaria and others.

Randomised
Yes
Open Label
Yes
Comparator
Placebo (Crinecerfont placebo for oral capsules) as comparator arm; active arm: Crinecerfont (NBI-74788) 100 mg twice daily (bid).
Target Sample Size
83

Eligibility

Recruits 83 Vulnerable population selected. All participants must provide written informed consent. Enrollment restricted to adults (≥18 years) so no child assent procedures are described. Subject information and informed consent forms and related materials are provided (multiple country-specific versions listed in the trial documents)..

Pregnancy Exclusion
Females who are pregnant or lactating.
Vulnerable Population
Vulnerable population selected. All participants must provide written informed consent. Enrollment restricted to adults (≥18 years) so no child assent procedures are described. Subject information and informed consent forms and related materials are provided (multiple country-specific versions listed in the trial documents).

Inclusion criteria

  • {"criterion_text":"- Subjects must provide written informed consent.\n- Be a female or male at least 18 years of age.\n- Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency.\n- Be on a stable, supraphysiologic glucocorticoid dose regimen that has been stable for at least 1 month prior to screening.\n- If treated with fludrocortisone, dose should be stable for at least 1 month prior to screening with an upright plasma renin activity (PRA) during screening that is not greater than ULN on the subject's usual sodium intake. If PRA is >ULN, the subject must have systolic blood pressure >100 mmHg, without orthostatic hypotension, and with serum sodium and potassium in the normal range.\n- Female subjects of childbearing potential with fertile male partners must agree to use contraception consistently from screening until the final study visit or 30 days after the last dose of study drug, whichever is longer. A female who is not of childbearing potential must meet one of the following:"}

Exclusion criteria

  • {"criterion_text":"- Have a known or suspected diagnosis of any of the other forms of classic CAH including 11-β-hydroxylase deficiency, 17-α-hydroxylase deficiency, 3-β-hydroxysteroid dehydrogenase deficiency, P450 sidechain cleavage deficiency, or P450 oxidoreductase deficiency.\n- Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic therapy with oral glucocorticoids, or requiring chronic therapy with inhaled glucocorticoids that based on dose and hormone profile the investigator deems would yield significant systemic exposure interfering with study endpoints.\n- Have a clinically significant medical condition or chronic disease (including history of neurological, hepatic, renal, cardiovascular, gastrointestinal, significant malabsorption, hematologic, pulmonary, psychiatric, or endocrine disease [excluding CAH]) that in the opinion of the investigator would preclude the subject from participating in and completing the study or that could confound interpretation of study outcome.\n- History of malignancy, unless successfully treated with curative intent and considered to be cured.\n- Have a known history of clinically concerning cardiac arrhythmia (including long QT syndrome) or prolongation of screening (pretreatment) QT interval corrected for heart rate using Fridericia's correction (QTcF) of >450 msec (males) or >470 msec (females).\n- Known sensitivity (ie, hypersensitivity) or allergy to any corticotropinreleasing hormone (CRH) receptor antagonist.\n- Have evidence of chronic renal or liver disease Used any active investigational drug within 30 days or 5 half-lives (whichever is longer) before screening, or plans to use an investigational drug (other than the study drug) during the study.\n- Females who are pregnant or lactating.\n- Are using any excluded concomitant medication and cannot discontinue use of these medications for the duration of the study (also refer to Section 9.9.1): • Orally administered glucocorticoids for indications other than CAH. • Strong inducers of CYP3A4 or CYP2B6 except topically administered medications. • Medications that affect cortisol or glucocorticoid metabolism (eg, phenytoin, mitotane, phenobarbital, strong CYP3A4 inhibitors such as ketoconazole, clarithromycin, cholestyramine, certain antivirals) except topically administered medications. • Aromatase inhibitors (eg, anastrozole, letrozole, testolactone)."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Percent change from baseline in glucocorticoid daily dose (in hydrocortisone equivalents adjusted for BSA [mg/m2/day]) at Week 24.","definition_or_measurement_approach":"Percent change from baseline in glucocorticoid daily dose measured in hydrocortisone equivalents adjusted for body surface area (mg/m2/day), assessed at Week 24."}

Secondary endpoints

  • {"endpoint_text":"- Change from baseline in serum androstenedione at Week 4.","definition_or_measurement_approach":"Change from baseline in serum androstenedione level measured at Week 4."}
  • {"endpoint_text":"- Achievement of a reduction in glucocorticoid daily dose to physiologic levels Week 24.","definition_or_measurement_approach":"Proportion/occurrence of subjects whose glucocorticoid daily dose is reduced to physiologic levels by Week 24."}
  • {"endpoint_text":"- Changes from baseline in HOMA-IR, weight, and fat mass at Week 24","definition_or_measurement_approment":"Changes from baseline in HOMA-IR, body weight, and fat mass assessed at Week 24."}

Recruitment

Planned Sample Size
83
Recruitment Window Months
80
Consent Approach
Written informed consent is required from all participants ("Subjects must provide written informed consent."). Participants are adults (≥18 years) so no assent is described. Subject information and informed consent forms (including pregnancy, genetic testing, data protection variants) are provided in multiple country-specific versions as listed in the trial documents.

Geography

Total Number Of Sites
31
Total Number Of Participants
99

Austria

Earliest CTIS Part Ii Submission Date
03-07-2024
Latest Decision Or Authorization Date
16-06-2025
Processing Time Days
348
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Allgemeines Krankenhaus Der Stadt Wien Universitatskliniken
Department Name
Department of Internal Medicine III
Principal Investigator Name
Florian Kiefer
Principal Investigator Email
florian.kiefer@meduniwien.ac.at
Contact Person Name
Florian Kiefer
Site Name
Medical University Of Graz
Department Name
Klinische Abteilung für Endokrinologie und Diabetologie Universitätsklinik für Innere Medizin
Principal Investigator Name
Stefan Pilz
Principal Investigator Email
stefan.pilz@medunigraz.at
Contact Person Name
Stefan Pilz
Contact Person Email
stefan.pilz@medunigraz.at

Belgium

Earliest CTIS Part Ii Submission Date
09-07-2024
Latest Decision Or Authorization Date
11-06-2025
Processing Time Days
337
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
UZ Leuven
Department Name
University Hospital Leuven
Principal Investigator Name
Leen Antonio
Principal Investigator Email
leen.antonio@uzleuven.be
Contact Person Name
Leen Antonio
Contact Person Email
leen.antonio@uzleuven.be

Bulgaria

Earliest CTIS Part Ii Submission Date
08-07-2024
Latest Decision Or Authorization Date
13-06-2025
Processing Time Days
340
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
University Specialized Hospital For Active Treatment In Endocrinology Akad. Iv. Penchev EAD
Department Name
First Clinic
Principal Investigator Name
Ralitsa Robeva
Principal Investigator Email
rali_robeva@yahoo.com
Contact Person Name
Ralitsa Robeva
Contact Person Email
rali_robeva@yahoo.com

Czechia

Earliest CTIS Part Ii Submission Date
04-07-2024
Latest Decision Or Authorization Date
13-06-2025
Processing Time Days
344
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Fakultni Nemocnice Hradec Kralove
Department Name
IV. Interní klinika
Principal Investigator Name
Jan Čáp
Principal Investigator Email
capj@lfhk.cuni.cz
Contact Person Name
Jan Čáp
Contact Person Email
capj@lfhk.cuni.cz

France

Earliest CTIS Part Ii Submission Date
05-07-2024
Latest Decision Or Authorization Date
13-06-2025
Processing Time Days
343
Number Of Sites
6
Number Of Participants
16

Sites

Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
-
Principal Investigator Name
Justine Cristante
Principal Investigator Email
jcristante@chu-grenoble.fr
Contact Person Name
Justine Cristante
Contact Person Email
jcristante@chu-grenoble.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Endocrinology
Principal Investigator Name
Philippe Touraine
Principal Investigator Email
philippe.touraine@aphp.fr
Contact Person Name
Philippe Touraine
Contact Person Email
philippe.touraine@aphp.fr
Site Name
Centre Hospitalier Regional D'Angers
Department Name
CHU Angers
Principal Investigator Name
Patrice Rodien
Principal Investigator Email
parodien@chu-angers.fr
Contact Person Name
Patrice Rodien
Contact Person Email
parodien@chu-angers.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Endocrinology
Principal Investigator Name
Delphine Drui
Principal Investigator Email
Delphine.DRUI@chu-nantes.fr
Contact Person Name
Delphine Drui
Contact Person Email
Delphine.DRUI@chu-nantes.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Endocrinology
Principal Investigator Name
Jerome Bertherat
Principal Investigator Email
jerome.bertherat@aphp.fr
Contact Person Name
Jerome Bertherat
Contact Person Email
jerome.bertherat@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service of endocrinology adults BuldingBarré-Sinoussi
Principal Investigator Name
Jacques Young
Principal Investigator Email
jacques.young@aphp.fr
Contact Person Name
Jacques Young
Contact Person Email
jacques.young@aphp.fr

Germany

Earliest CTIS Part Ii Submission Date
04-07-2024
Latest Decision Or Authorization Date
13-06-2025
Processing Time Days
344
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Endocrinology department
Principal Investigator Name
Nicole Reisch
Principal Investigator Email
nicole.reisch@med.uni-muenchen.de
Contact Person Name
Nicole Reisch
Site Name
Goethe University Frankfurt
Department Name
Endocrinology - Diabetology
Principal Investigator Name
Jörg Bojunga
Principal Investigator Email
joerg.bojunga@ukffm.de
Contact Person Name
Jörg Bojunga
Contact Person Email
joerg.bojunga@ukffm.de

Greece

Earliest CTIS Part Ii Submission Date
23-09-2024
Latest Decision Or Authorization Date
16-06-2025
Processing Time Days
266
Number Of Sites
3
Number Of Participants
6

Sites

Site Name
Ippokratio General Hospital Of Thessaloniki
Department Name
A' Department of Internal Medicine NHS – Endocrinology Clinic
Principal Investigator Name
Zoe Efstathiadou
Principal Investigator Email
zefsta@hotmail.com
Contact Person Name
Zoe Efstathiadou
Contact Person Email
zefsta@hotmail.com
Site Name
Laiko General Hospital Of Athens
Department Name
A' Propaepeudic Department of Internal Medicine - Endocrinology University Clinic
Principal Investigator Name
Gregory Kaltsas
Principal Investigator Email
gregory.kaltsas@gmail.com
Contact Person Name
Gregory Kaltsas
Contact Person Email
gregory.kaltsas@gmail.com
Site Name
Evangelismos S.A.
Department Name
Endocrinology Department – Diabetes and Metabolism (AHEPA building, 8th floor),
Principal Investigator Name
Vassiliadi Dimitra
Principal Investigator Email
d.a.vassiliadi@gmail.com
Contact Person Name
Vassiliadi Dimitra
Contact Person Email
d.a.vassiliadi@gmail.com

Italy

Earliest CTIS Part Ii Submission Date
10-07-2024
Latest Decision Or Authorization Date
16-06-2025
Processing Time Days
341
Number Of Sites
8
Number Of Participants
36

Sites

Site Name
University Of Florence
Department Name
Endocrinology Unit, Dept. of Experimental and Clinical Biomedical Sciences "Mario Serio"
Principal Investigator Name
Mario Maggi
Principal Investigator Email
mario.maggi@unifi.it
Contact Person Name
Mario Maggi
Contact Person Email
mario.maggi@unifi.it
Site Name
Azienda Unita Sanitaria Locale Di Bologna
Department Name
UOC di Endocinologia
Principal Investigator Name
Uberto Pagotto
Principal Investigator Email
uberto.pagotto@unibo.it
Contact Person Name
Uberto Pagotto
Contact Person Email
uberto.pagotto@unibo.it
Site Name
Azienda Ospedaliera di Padova
Department Name
Department of Medicine DIMED
Principal Investigator Name
Mattia Barbot
Principal Investigator Email
mattia.barbot@aopd.veneto.it
Contact Person Name
Mattia Barbot
Contact Person Email
mattia.barbot@aopd.veneto.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Department of Pediatric Endocrinology.
Principal Investigator Name
Gianni Russo
Principal Investigator Email
russo.gianni@hsr.it
Contact Person Name
Gianni Russo
Contact Person Email
russo.gianni@hsr.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
Clinica medica 5, department of Experimental Medicine
Principal Investigator Name
Andrea Isidori
Principal Investigator Email
andrea.isidori@uniroma1.it
Contact Person Name
Andrea Isidori
Contact Person Email
andrea.isidori@uniroma1.it
Site Name
Istituto Auxologico Italiano IRCCS
Department Name
Department of Endocrine and Metabolic Diseases
Principal Investigator Name
Luca Persani
Principal Investigator Email
luca.persani@unimi.it
Contact Person Name
Luca Persani
Contact Person Email
luca.persani@unimi.it
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Clinica di Endocrinologia, Dipartimento di Specialità Mediche e Chirurgiche
Principal Investigator Name
Gilberta Giacchetti
Contact Person Name
Gilberta Giacchetti
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
Department of Clinical Medicine and Surgery, section of Endocrinology
Principal Investigator Name
Rosario Pivonello
Principal Investigator Email
rosario.pivonello@unina.it
Contact Person Name
Rosario Pivonello
Contact Person Email
rosario.pivonello@unina.it

Poland

Earliest CTIS Part Ii Submission Date
23-07-2024
Latest Decision Or Authorization Date
16-06-2025
Processing Time Days
328
Number Of Sites
3
Number Of Participants
11

Sites

Site Name
Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o.o.
Department Name
-
Principal Investigator Name
Grzegorz Sokołowski
Principal Investigator Email
grzegorz.sokolowski@dobrylekarz.com.pl
Contact Person Name
Grzegorz Sokołowski
Site Name
Uniwersytecki Szpital Kliniczny W Poznaniu
Department Name
-
Principal Investigator Name
Marek Ruchala
Principal Investigator Email
mruchala@ump.edu.pl
Contact Person Name
Marek Ruchala
Contact Person Email
mruchala@ump.edu.pl
Site Name
Szpital Bielanski Im.Ks.Jerzego Popieluszki Samodzielny Publiczny Zaklad Opieki Zdrowotnej
Department Name
-
Principal Investigator Name
Lucyna Bednarek-Papierska
Principal Investigator Email
lbednarek@cmkp.edu.pl
Contact Person Name
Lucyna Bednarek-Papierska
Contact Person Email
lbednarek@cmkp.edu.pl

Portugal

Earliest CTIS Part Ii Submission Date
05-07-2024
Latest Decision Or Authorization Date
11-06-2025
Processing Time Days
341
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Sao Joao University Hospital Center
Department Name
Endocrinology Department
Principal Investigator Name
Duarte Pigniatelli
Principal Investigator Email
dpignatelli@yahoo.com
Contact Person Name
Duarte Pigniatelli
Contact Person Email
dpignatelli@yahoo.com

Spain

Earliest CTIS Part Ii Submission Date
05-07-2024
Latest Decision Or Authorization Date
13-06-2025
Processing Time Days
343
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Endocrinology and Nutrition Department
Principal Investigator Name
Manuel Luque Ramírez
Principal Investigator Email
manuel.luque@salud.madrid.org
Contact Person Name
Manuel Luque Ramírez
Contact Person Email
manuel.luque@salud.madrid.org
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
-
Principal Investigator Name
Miguel Mangas Cruz
Principal Investigator Email
mangel.mangas.sspa@juntadeandalucia.es
Contact Person Name
Miguel Mangas Cruz

Sweden

Earliest CTIS Part Ii Submission Date
03-07-2024
Latest Decision Or Authorization Date
16-06-2025
Processing Time Days
348
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Karolinska University Hospital
Department Name
Department of Endocrinology, Metabolism and Diabetes
Principal Investigator Name
Henrik Falhammar
Principal Investigator Email
henrik.falhammar@ki.se
Contact Person Name
Henrik Falhammar
Contact Person Email
henrik.falhammar@ki.se

Sponsor

Primary sponsor

Full Name
Neurocrine Biosciences Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Worldwide Clinical Trials Holdings Inc.
Responsibilities
Medical monitoring, Site Management, Site Activation including Negotiation of site clinical trial agreements, Trial Master File, Clinical Assessment Technologies, Risk Based Quality Management (RBQM), Drug Safety, Grant and Vendor Payments
Name
Syneos Health Inc.
Responsibilities
PK Analysis
Name
Medpace Inc.
Responsibilities
Analysis of urine androgen metabolites
Name
Bioclinica Inc.
Responsibilities
Medical image review and analysis: DXA, ultrasound , Blood pressure equipment provider
Name
Medpace Reference Laboratories LLC
Responsibilities
Processing and analysis of blood and urine samples, Clinical hematology, chemistry Biomarker analyses
Name
Quest Diagnostics Nichols Institute Inc.
Responsibilities
Analysis of 17-OHP, PRA, ASD, CYP21A2, Total testosterone

Third parties

  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image review and analysis: DXA, ultrasound , Blood pressure equipment provider","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Quest Diagnostics Nichols Institute Inc.","duties_or_roles":"Analysis of 17-OHP, PRA, ASD, CYP21A2, Total testosterone","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"Processing and analysis of blood and urine samples, Clinical hematology, chemistry Biomarker analyses","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"Data Monitoring Committee (DMC)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"e-PRO (electronic patient-reported outcome) related services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"Analysis of urine androgen metabolites","organisation_type":"Pharmaceutical company"}
  • {"country":"Israel","full_name":"Trialog Clinical Trials Ltd.","duties_or_roles":"Depot for IP distribution and return in Israel","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"PK Analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"electronic patient-reported outcome (e-PRO) and related services","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"Home health services, Direct-to-Patient (DTP) IP shipments","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"Clinical hematology, chemistry Biomarker analyses, Processing and analysis of blood, urine samples","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom","full_name":"Biotec Services International Limited","duties_or_roles":"IP distribution and labeling","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Millmount Healthcare Limited","duties_or_roles":"IP distribution and labeling","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Andersonbrecon Inc.","duties_or_roles":"IP distribution and labeling","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Worldwide Clinical Trials Holdings Inc.","duties_or_roles":"Medical monitoring, Site Management, Site Activation including Negotiation of site clinical trial agreements, Trial Master File, Clinical Assessment Technologies, Risk Based Quality Management (RBQM), Drug Safety, Grant and Vendor Payments","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Central Institutional Review Board (IRB)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
NBI-74788
Active Substance
CRINECERFONT
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
Oral
Authorisation Status
prodAuthStatus=1
Orphan Designation
Yes
Starting Dose
100 mg twice daily (bid)
Dose Levels
100 mg twice daily
Frequency
Twice daily (bid)
Investigational Product Name
Crinecerfont placebo for oral capsules
Modality
Other

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