E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Classic Congenital Adrenal Hyperplasia (CAH) |
Hiperplasia Suprarrenal Congénita Clásica |
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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. |
Hiperplasia suprarrenal congénita(CAH) es 1 grupo de trastornos endocrinos hereditarios poco frecuentes caracterizado por la deficiencia de una enzima necesaria para producir hormonas específicas. |
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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 | 100000004850 |
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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, compared with placebo, in reducing adrenal steroid levels during a glucocorticoid-stable period. • To evaluate the efficacy of crinecerfont, compared with placebo, in reducing daily glucocorticoid dosage while maintaining adrenal androgen control. • To evaluate the effect of crinecerfont, compared with placebo, on clinical endpoints associated with supraphysiologic glucocorticoid dosing and androgen excess. • To evaluate plasma concentrations of crinecerfont and metabolites. • To assess the safety and tolerability of crinecerfont. |
• Evaluar la eficacia de crinecerfont, en comparación con placebo, en la reducción de los niveles de esteroides suprarrenales durante un periodo estable con glucocorticoides. • Evaluar la eficacia de crinecerfont, en comparación con placebo, en la reducción de la dosis diaria de glucocorticoides mientras se mantiene el control androgénico suprarrenal. • Evaluar el efecto de crinecerfont, en comparación con placebo, en los criterios de valoración clínicos asociados a la administración suprafisiológica de glucocorticoides y el exceso de andrógenos. • Evaluar las concentraciones plasmáticas de crinecerfont y sus metabolitos. • Evaluar la seguridad y la tolerabilidad de crinecerfont. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Be willing and able to adhere to the study procedures, including all requirements at the study center and return for the follow-up visit. - Be a female or male 2 to 17 years of age with a body weight of at least 10 kg. - Have a medically confirmed diagnosis of classic CAH due to 21- hydroxylase deficiency. - Be on a stable regimen of glucocorticoid treatment for CAH. - Have elevated adrenal androgens. - If treated with fludrocortisone, be on a stable regimen with plasma renin activity (PRA) indicating adequate replacement. |
- Estar dispuesto y ser capaz de cumplir con los procedimientos del estudio, incluidos todos los requisitos en el centro del estudio y relizar la visita de seguimiento. - Ser mujer o hombre de 2 a 17 años con un peso corporal de al menos 10 kg. - Tener un diagnóstico médicamente confirmado de CAH clásica por deficiencia de 21-hidroxilasa. - Estar en un régimen estable de tratamiento con glucocorticoides para la CAH. - Tener andrógenos suprarrenales elevados. - Si se trata con fludrocortisona, mantenerse en un régimen estable con actividad de renina plasmática (ARP) que indique un reemplazo adecuado. |
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E.4 | Principal exclusion criteria |
- Have a diagnosis of any of the other forms of classic CAH. - Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic daily therapy with oral glucocorticoids. - Have a clinically significant unstable medical condition or chronic disease other than CAH - Have a history of malignancy, unless successfully treated with curative intent and considered to be cured. - Have a known history of clinically significant arrhythmia or abnormalities on screening ECG. - Have a known hypersensitivity or allergy to any corticotropin-releasing hormone (CRH) receptor antagonist. - Females who are pregnant or lactating. |
- Tener un diagnóstico de cualquiera de las otras formas de CAH clásica. - Tener antecedentes de adrenalectomía bilateral, hipopituitarismo u otra afección que requiera tratamiento diario crónico con glucocorticoides orales. - Tener una condición médica inestable clínicamente significativa o una enfermedad crónica que no sea CAH - Tener antecedentes de malignidad, a menos que se trate con éxito con intención curativa y se considere curado. - Tener antecedentes conocidos de arritmias o anomalías clínicamente significativas en el ECG de detección. - Tener hipersensibilidad conocida o alergia a cualquier antagonista del receptor de la hormona liberadora de corticotropina (CRH). - Mujeres embarazadas o en período de lactancia. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in serum androstenedione at Week 4. |
Cambio del valor inicial en la androstenediona sérica en la semana 4. |
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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) |
- Percent change from baseline in glucocorticoid dose at Week 28 - Change from baseline in serum 17-hydroxyprogesterone at Week 4 |
- Cambio porcentual desde el valor inicial en la dosis de glucocorticoides en la semana 28 - Cambio con respecto al valor inicial en la 17-hidroxiprogesterona sérica en la semana 4 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 4 and Week 28 |
Semana 4 y Semana 28 |
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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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 21 |
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 |
Canada |
United States |
Belgium |
France |
Germany |
Italy |
Poland |
Spain |
Sweden |
Greece |
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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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |