E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Classic Congenital Adrenal Hyperplasia (CAH) |
Класическа вродена надбъбречна хиперплазия |
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E.1.1.1 | Medical condition in easily understood language |
Congenital adrenal hyperplasia (CAH) is a group of rare inherited endocrine disorders characterized by a deficiency of one of the enzymes needed to make specific hormones |
Вродената надбъбречна хиперплазия е група от редки наследствени ендокринни заболявания, характеризиращи се с дефицит на един от ензимите, необходими за производството на специфични хормони |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010323 |
E.1.2 | Term | Congenital adrenal hyperplasia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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.
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• Да се оцени ефикасността на crinecerfont (100 mg два пъти дневно [bid]) в сравнение с плацебо за намаляване на дневната доза глюкокортикоиди при поддържане на контрол на надбъбречните андрогени. • Да се оцени ефикасността на crinecerfont в сравнение с плацебо за понижаване на нивата на надбъбречните стероиди след първоначален 4-седмичен период на лечение. • Да се оцени ефекта на crinecerfont в сравнение с плацебо върху клиничните крайни точки, свързани със супрафизиологични дози глюкокортикоиди. •Да се оценят плазмените концентрации на crinecerfont и метаболитите. •Да се оцени безопасността и поносимостта на crinecerfont. • Да се оцени алтернативна схема на дозиране на crinecerfont при участници, които не са намалили дозата на глюкокортикоидите до Месец 12.
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Не е приложимо |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (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 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 subject who is not of childbearing potential must meet one of the following: Postmenopausal Permanent sterilization procedure. |
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E.4 | Principal exclusion criteria |
• Have a known or suspected diagnosis of any of the other forms of classic CAH including 11-β-hydroxylase deficiency, 17-α-hydroxylase deficiency, 3-β-hydroxysteroid dehydrogenase deficiency, P450 side-chain cleavage deficiency, or P450 oxidoreductase deficiency. • Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiringchronic therapy with oral glucocorticoids, or requiring chronic therapy with inhaledglucocorticoids that based on dose and hormone profile the investigator deems would yieldsignificant 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 thesemedications 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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in glucocorticoid daily dose (in hydrocortisone equivalents adjusted for BSA [mg/m2/day]) at Week 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Ukraine |
Israel |
Serbia |
United Kingdom |
United States |
Austria |
Belgium |
Bulgaria |
Czechia |
France |
Germany |
Greece |
Italy |
Netherlands |
Poland |
Portugal |
Spain |
Sweden |
Türkiye |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS |
последно посещение последен пациент |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |