Evaluation of Pharmacokinetics, Safety, and Tolerability of Crinecerfont in Pediatric Patients Aged 0 to <2 Years with Congenital Adrenal Hyperplasia
- Trial ID
- 2024-514127-42-00
- Protocol
- NBI-74788-CAH2011
- Sponsor
- Neurocrine Switzerland GmbH
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **pharmacokinetics** (PK) of crinecerfont in pediatric subjects aged 0 to less than 2 years with **congenital adrenal hyperplasia** (CAH). Understanding the PK profile is clinically relevant as it provides critical information on the absorption, distribution, metabolism, and excretion of crinecerfont in this specific patient population, which is essential for optimizing dosing regimens and ensuring therapeutic efficacy.
The secondary objective is to assess the safety and tolerability of crinecerfont in the same pediatric cohort. Evaluating safety and tolerability is crucial to identify any potential adverse effects and to ensure that the treatment is well-tolerated by young patients, thereby supporting its use in clinical practice for managing CAH in this age group.
Participants
The clinical trial involves a study population of pediatric subjects aged 0 to less than 2 years, diagnosed with **congenital adrenal hyperplasia** (CAH). Both male and female participants are included in the trial, and the population is considered vulnerable due to the young age of the subjects. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific criteria, including a medically confirmed diagnosis of classic CAH due to 21-hydroxylase deficiency, and a body weight of at least 3.0 kg at screening. Subjects must be on a clinically stable regimen of hydrocortisone, with or without fludrocortisone, expected to remain stable throughout the treatment period. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection process ensures that participants have a 17-hydroxyprogesterone level greater than twice the upper limit of normal, and a normal newborn screen except for elevated 17-OHP, among other criteria. The trial aims to evaluate the pharmacokinetics of crinecerfont in this specific population.
Plans and Procedures
The clinical trial is designed to evaluate the **pharmacokinetics** (PK), safety, tolerability, and pharmacodynamics of **crinecerfont** in pediatric subjects aged 0 to less than 2 years with **congenital adrenal hyperplasia** (CAH). This is a Phase II, open-label study, which means that both the researchers and participants know which treatment is being administered. The trial is expected to commence recruitment on June 26, 2025, and is estimated to conclude by December 9, 2029. The study involves the administration of crinecerfont as an oral solution, with a maximum treatment period of 158 days.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, body weight, and a medically confirmed diagnosis of classic CAH. The primary endpoint of the study is to measure plasma concentrations of crinecerfont on Days 7 and 15, while secondary endpoints include the incidence of treatment-emergent adverse events (TEAEs). The study will involve a 14-day treatment period, during which participants will be on a clinically stable regimen of hydrocortisone, with or without fludrocortisone, as applicable.
Study visits will include follow-up assessments to monitor the safety and efficacy of the treatment. The end-of-study visit will mark the completion of the participant's involvement in the trial. Participants are expected to remain in the study for the entire duration unless conditions arise that necessitate early termination, such as adverse reactions or non-compliance with study procedures. The trial is conducted under the authorization of relevant regulatory bodies, ensuring adherence to ethical standards and scientific rigor.
Treatment
The clinical trial involves the administration of the experimental medication **NBI-74788**, which contains the active substance **crinecerfont**. This medication is provided in the form of an **oral solution** and is intended for pediatric subjects aged 0 to less than 2 years with **congenital adrenal hyperplasia**. The pharmaceutical form of the medication is specifically designed for oral administration. The dosing regimen, including the specific dosage and frequency of administration, is determined by the study protocol, although the maximum daily and total dose amounts are not specified in the provided data. The maximum treatment period for the administration of NBI-74788 is 158 days. The medication is classified as a chemical substance and is not a pediatric formulation. The study is conducted under the sponsorship of Neurocrine Biosciences Inc., and the medication has been designated as an orphan drug with the designation number EU/3/19/2194.
In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment, as per the study protocol. However, specific details regarding these non-experimental treatments are not provided in the available data. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The study aims to evaluate the pharmacokinetics, safety, tolerability, and pharmacodynamics of crinecerfont in the specified pediatric population.
Efficacy
The efficacy of the investigational product, **crinecerfont**, will be assessed in a Phase 2, open-label clinical trial involving pediatric subjects aged 0 to less than 2 years with Congenital Adrenal Hyperplasia (CAH). The primary endpoint for evaluating efficacy is the measurement of plasma concentrations of crinecerfont on Days 7 and 15. These measurements will provide critical data on the pharmacokinetics of the drug in the target population. The secondary endpoint includes the incidence of treatment-emergent adverse events (TEAEs), which will be monitored to assess the safety and tolerability of the treatment. The collection and analysis of these endpoints will be conducted according to the study protocol, ensuring that the data is robust and reliable for evaluating the efficacy of crinecerfont in this specific patient group.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- Be a female or male between 0 to <2 years of age at screening.
- Have a body weight of at least 3.0 kg at screening.
- 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.
- 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).
- 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.
- 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.
- Regardless of fludrocortisone treatment, but in the absence of medications that confound interpretation of PRA, PRA (collected upright when appropriate for age) <2 × ULN.
- The subject’s parent(s) or legal guardian(s) is willing to follow study procedures.
Exclusion Criteria
- 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.
- Have a history of bilateral adrenalectomy or hypopituitarism.
- 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.
- Have hyponatremia (serum sodium ≤135 mM), serum potassium ≥ULN for age, or bicarbonate ≤18 mM.
- 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
- Have any condition besides CAH that requires chronic daily therapy with orally administered steroids.
- Have a malignancy or a history of malignancy.
- 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.
- 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.
- Have a known sensitivity (ie, hypersensitivity) or allergy to any corticotropin-releasing hormone receptor antagonist or any component of the study drug.
- 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
- 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
- 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.
- 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.
- Using any excluded concomitant medication (as defined in Section 7.1) and cannot discontinue use of these medications for the duration of the study.
- 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.
- 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).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 26 Jun 2025 | 10 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
NBI-74788 | Test | ORAL SOLUTION | ORAL | 00 | 158 | PRD7537534 |