Crinecerfont for Congenital adrenal hyperplasia

Inclusion criteria

• {"criterion_text":"- Completed informed consent from the subject’s parent(s) or legal guardian in accordance with the governing IRB/IEC and according to local laws and regulations.\n- Be a female or male between 0 to <2 years of age at screening.\n- Have a body weight of at least 3.0 kg at screening.\n- Have a medically confirmed diagnosis of classic CAH (salt wasting or simple virilizing) due to 21-OHD deficiency based on standard medically accepted criteria, including the clinical presentation in addition to elevated 17-OHP concentration (either at baseline or after cosyntropin stimulation testing). Additional confirmation of the diagnosis includes a confirmed cytochrome P450 (CYP)21A2 genotype if available.\n- Have a 17-OHP level (prior to the morning hydrocortisone dose) >2 × the upper limit of normal (ULN) according to sex and either age (for Tanner stage 1) or pubertal stage (for Tanner stages 2 to 5); Tanner stage will be determined by breast/genital development (not pubic hair).\n- Have a newborn screen that is otherwise normal except for elevated 17-OHP or any other abnormality on newborn screen that was cleared upon evaluation by a pediatric specialist.\n- Be on a clinically stable regimen of hydrocortisone (and fludrocortisone, if applicable) treatment for CAH that is expected to remain stable throughout the 14-Day Treatment Period. Adjustments to the dosing regimen needed to adhere to the protocol requirements for sample collection are allowed.\n- Regardless of fludrocortisone treatment, but in the absence of medications that confound interpretation of PRA, PRA (collected upright when appropriate for age) <2 × ULN.\n- The subject’s parent(s) or legal guardian(s) is willing to follow study procedures."}

Exclusion criteria

• {"criterion_text":"- Have a known or suspected diagnosis of any of the other forms of classic CAH including 11β-hydroxylase deficiency, 17α-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, P450 side-chain cleavage deficiency, or P450 oxidoreductase deficiency.\n- Have a history of bilateral adrenalectomy or hypopituitarism.\n- Are at increased risk of developing adrenal crisis in the investigator’s opinion, based on, for example, repeated history of adrenal crisis in the past, prior history of adrenal crisis precipitated by reducing hydrocortisone dose, recent episode(s), etc.\n- Have hyponatremia (serum sodium ≤135 mM), serum potassium ≥ULN for age, or bicarbonate ≤18 mM.\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 or that could affect the absorption or elimination of crinecerfont\n- Have any condition besides CAH that requires chronic daily therapy with orally administered steroids.\n- Have a malignancy or a history of malignancy.\n- Have a history of prematurity (defined as delivery before 37 weeks’ gestational age) and has not reached full term (ie, original due date) before screening.\n- Have a known history of clinically concerning cardiac arrhythmia (including long QT syndrome) or prolongation of QT interval corrected for heart rate using Fridericia’s correction (QTcF) of >450 msec (males) or >470 msec (females) per electrocardiogram (ECG) at screening.\n- Have evidence of chronic renal or liver disease based on any of these screening laboratory test abnormalities: - Estimated glomerular filtration rate <60% mean GFR value for age (Jančič et al, 2022) Abnormal liver function\n- Have any of the following hematologic abnormalities at screening: •\tHemoglobin <10 g/dL •\tWhite blood cell (WBC) count <4.0 × 103/mm3 •\tPlatelet count <100,000/mm3 •\tAbsolute neutrophil count <1.0 × 103/mm3\n- Are breastfed by a mother who used crinecerfont, orally administered glucocorticoids, or any of the prohibited medications listed in Section 7.1 within 30 days or 5 half-lives (whichever is longer) before screening or who plans to use any of these medications during the study.\n- Used any active investigational drug in the context of a clinical trial within 30 days or 5 half- lives (whichever is longer) before screening or the parent(s) or guardian(s) plans to give the subject an investigational drug (other than crinecerfont) during the study.\n- Using any excluded concomitant medication (as defined in Section 7.1) and cannot discontinue use of these medications for the duration of the study.\n- Have had a blood loss ≥3% of the subject’s total blood volume (calculated based on total blood volume of 80 to 90 mL blood per 1 kg body weight and in neonates 100 mL/kg of body weight) within 8 weeks before the screening visit.\n- In the investigator’s opinion, the family of the subject is not capable of adhering to the protocol requirements (eg, ongoing and persistent noncompliance with hydrocortisone therapy)."}

Primary endpoints

• {"endpoint_text":"- Plasma concentrations of crinecerfont at Days 7 and 15","definition_or_measurement_approach":"Plasma concentrations measured on Days 7 and 15 (pharmacokinetic sampling to evaluate PK of crinecerfont)."}

Secondary endpoints

• {"endpoint_text":"- Incidence of treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":"Recording and summarising incidence of treatment-emergent adverse events during the study (safety and tolerability assessment)."}

Germany

Earliest CTIS Part Ii Submission Date

10-06-2025

Latest Decision Or Authorization Date

11-11-2025

Processing Time Days

154

Number Of Sites

4

Number Of Participants

10

Primary sponsor

Full Name

Neurocrine Biosciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Fortrea Inc.

Responsibilities

Operational services (sponsorDuties code 8)

Name

Syneos Health Inc.

Responsibilities

PK laboratory analyses (Princeton); EC and RA applications, patient concierge services, patient reimbursement and other operational roles (Morrisville)

Name

MARKEN Germany GmbH

Responsibilities

Vendor direct-to-patient IP courier services

Name

LabConnect GmbH

Responsibilities

Central laboratory and laboratory services

Name

Cytel Inc.

Responsibilities

Independent Statistical Center supporting Data Monitoring Committee (DMC)

Name

Medidata Solutions Inc.

Responsibilities

e-PRO and E-data capture

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc. (Princeton)","duties_or_roles":"PK Laboratory analyses","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"Vendor direct-to-patient IP courier services","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"LabConnect GmbH","duties_or_roles":"Central Laboratory; code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"Independent Statistical Center supporting Data Monitoring Committee (DMC)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc. (Morrisville)","duties_or_roles":"EC and RA applications, Patient concierge services and patient reimbursement; other operational roles (codes 1,11,12,15,2,5,8)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"electronic patient-reported outcome (e-PRO) E-data capture","organisation_type":"Non-Pharmaceutical company"}