Pharmacokinetics, safety, and tolerability of crinecerfont in subjects with congenital adrenal hyperplasia who are less than 2 years old

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Neurocrine Biosciences Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

16 Oct 2025 → ongoing

Decision date (initial)

2025-07-01

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Neurocrine Biosciences, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Pharmacodynamic, Safety

The primary objective for this study is to evaluate the PK of crinecerfont in pediatric subjects 0 to <2 years of age with CAH.

Secondary objectives 1

1. The secondary objective for this study is to assess the safety and tolerability of crinecerfont in pediatric subjects 0 to <2 years of age with CAH.

Conditions and MedDRA coding

Congenital adrenal hyperplasia (CAH)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002700-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. Be a female or male between 0 to <2 years of age at screening.
3. Have a body weight of at least 3.0 kg at screening.
4. 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.
5. 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).
6. 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.
7. 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.
8. Regardless of fludrocortisone treatment, but in the absence of medications that confound interpretation of PRA, PRA (collected upright when appropriate for age) <2 × ULN.
9. The subject’s parent(s) or legal guardian(s) is willing to follow study procedures.

Exclusion criteria 17

1. 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.
2. Have a history of bilateral adrenalectomy or hypopituitarism.
3. 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.
4. Have hyponatremia (serum sodium ≤135 mM), serum potassium ≥ULN for age, or bicarbonate ≤18 mM.
5. 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
6. Have any condition besides CAH that requires chronic daily therapy with orally administered steroids.
7. Have a malignancy or a history of malignancy.
8. 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.
9. 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.
10. Have a known sensitivity (ie, hypersensitivity) or allergy to any corticotropin-releasing hormone receptor antagonist or any component of the study drug.
11. 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
12. Have any of the following hematologic abnormalities at screening: • Hemoglobin <10 g/dL • White blood cell (WBC) count <4.0 × 103/mm3 • Platelet count <100,000/mm3 • Absolute neutrophil count <1.0 × 103/mm3
13. 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.
14. 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.
15. Using any excluded concomitant medication (as defined in Section 7.1) and cannot discontinue use of these medications for the duration of the study.
16. 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.
17. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Plasma concentrations of crinecerfont at Days 7 and 15

Secondary endpoints 1

1. Incidence of treatment-emergent adverse events (TEAEs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Neurocrine Biosciences Inc.

Sponsor organisation

Neurocrine Biosciences Inc.

Address

6027 Edgewood Bend Court

City

San Diego

Postcode

92130-8235

Country

United States

Scientific contact point

Organisation

Neurocrine Biosciences Inc.

Contact name

Neurocrine Medical Information Call Center

Public contact point

Organisation

Neurocrine Biosciences Inc.

Contact name

Neurocrine Medical Information Call Center

Third parties 7

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications