A study of safety and efficacy of NBI-74788 in Classic Congenital Adrenal Hyperplasia
- Conditions
- Classic Congenital Adrenal Hyperplasia (CAH)MedDRA version: 20.0Level: LLTClassification code 10010323Term: Congenital adrenal hyperplasiaSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2019-004873-17-PL
- Lead Sponsor
- eurocrine Biosciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 165
• 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 (defined as >13mg/m2/day in hydrocortisone dose equivalents) 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 within the normal range on the subject’s usual sodium intake.
• Female subjects of childbearing potential 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 subject who is not of childbearing potential must meet 1 of the following:
Postmenopausal
Permanent sterilization procedure.
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
• 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, inhaled, or intranasal glucocorticoids.
• 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.<br>• To evaluate the efficacy of Crinecerfont, compared with placebo, in reducing adrenal steroid levels following an initial 4-week treatment period.<br>• To evaluate the effect of Crinecerfont, compared with placebo, on clinical endpoints associated with supraphysiologic glucocorticoid dosing.<br>• To evaluate plasma concentrations of Crinecerfont and metabolites.<br>• To assess the safety and tolerability of Crinecerfont. <br>• To evaluate an alternate dosing regimen of Crinecerfont in subjects who have not reduced their glucocorticoid dose by Month 12.<br>;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 Outcome Measures
Name Time Method Secondary end point(s): - Change from baseline in serum androstenedione at Week 4<br>- Achievement of a reduction in glucocorticoid daily dose to physiologic levels Week 24<br>- 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