Classic Congenital Adrenal Hyperplasia (CAH) MedDRA version: 20.0 Level: LLT Classification code 10010323 Term: Congenital adrenal hyperplasia System Organ Class: 100000004850
Conditions
Sponsors
Neurocrine Biosciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subjects must provide written informed consent. • Be a female or male at least 18 years of age. • Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency. • Be on a stable, supraphysiologic glucocorticoid dose regimen that has been stable for at least 1 month prior to screening. • 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. • 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: Postmenopausal Permanent sterilization procedure • Male subjects must agree to use contraception consistently from screening until 90 days after the last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: • Have a known or suspected diagnosis of any of the other forms of classic CAH including 11-ß-hydroxylase deficiency, 17-a-hydroxylase deficiency, 3-ß-hydroxysteroid dehydrogenase deficiency, P450 side-chain cleavage deficiency, or P450 oxidoreductase deficiency. • 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. • 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. • History of malignancy, unless successfully treated with curative intent and considered to be cured. • Have a known history of clinically concerning cardiac arrhythmia (including long QT syndrome) or prolongation of screening (pre-treatment) QT interval corrected for heart rate using Fridericia’s correction (QTcF) of >450 msec (males) or >470 msec (females). • Known sensitivity (ie, hypersensitivity) or allergy to any corticotropin-releasing hormone (CRH) receptor antagonist. • 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. • Females who are pregnant or lactating. • 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of Crinecerfont (100 mg twice daily [bid]), compared with placebo, in reducing daily glucocorticoid dosage while maintaining adrenal androgen control. • To evaluate the efficacy of Crinecerfont, compared with placebo, in reducing adrenal steroid levels following an initial 4-week treatment period. • To evaluate the effect of Crinecerfont, compared with placebo, on clinical endpoints associated with supraphysiologic glucocorticoid dosing. • To evaluate plasma concentrations of Crinecerfont and metabolites. • To assess the safety and tolerability of Crinecerfont. • To evaluate an alternate dosing regimen of crinecerfont in subjects who have not reduced their glucocorticoid dose by Month 12.;Secondary Objective: Not applicable;Primary end point(s): • Percent change from baseline in glucocorticoid daily dose (in hydrocortisone equivalents adjusted for BSA [mg/m2/day]) at Week 24.;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in serum androstenedione at Week 4. - Achievement of a reduction in glucocorticoid daily dose to physiologic levels Week 24. - Changes from baseline in HOMA-IR, weight, and fat mass at Week 24.;Timepoint(s) of evaluation of this end point: Week 4 and Week 24 | — |
Countries
Austria, Belgium, Bulgaria, Czechia, Czech Republic, France, Germany, Greece, Italy, Netherlands, Poland, Portugal, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactRegulatory Unit
Accelsiors CRO and Consultancy Services Ltd
Outcome results
None listed