E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Classic Congenital Adrenal Hyperplasia |
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E.1.1.1 | Medical condition in easily understood language |
CAH is a serious, chronically debilitating, and life-threatening genetic disorder characterized by impaired adrenal synthesis of cortisol and overproduction of adrenal androgens |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
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 effect of tildacerfont in reducing A4 in subjects with CAH over 12 weeks |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the effect of tildacerfont on A4 levels in subjects with CAH over 12 weeks •To evaluate the effect of tildacerfont on 17-OHP levels in subjects with CAH over 12 weeks •To evaluate the effect of tildacerfonr in reducing TART(s) in male CAH subjects with TART(s) at baseline after 12 weeks on treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male and female subjects ≥ 18 years old at screening 2.Has a known childhood diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented (at any time) elevated 17-OHP and currently treated with HC, HC acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned GCs) 3.For subjects with the salt-wasting form of CAH, the subject is on a stable dose of mineralocorticoid replacement for ≥1 month before screening 4.Agrees to follow contraception guidelines. Male subjects must also agree to refrain from donating sperm throughout the treatment period and for 90 days after the last dose of study drug. 5. Is able to understand all study procedures and risks involved and provides written informed consent indicating willingness to comply with all aspects of the protocol |
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E.4 | Principal exclusion criteria |
1.Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21-hydroxylase deficiency) 2.Has a history that includes bilateral adrenalectomy or hypopituitarism 3.Has a history of allergy or hypersensitivity to tildacerfont, or any of its excipients or any other CRF1 receptor antagonist 4.Current treatment with dexamethasone as GC therapy for CAH 5.Is not adherent to GC or study drug dosing regimen during the Run-in Period (defined as taking <80% of expected doses based on drug accountability) 6.Shows clinical signs or symptoms of adrenal insufficiency 7.Has had a clinically significant unstable medical condition, medically significant illness, or chronic disease occurring within 30 days of screening, including but not limited to: a. An ongoing malignancy or <3 years of remission history from any malignancy, other than successfully treated localized skin cancer b. Estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m2 c.Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at screening 8.Had or has a clinically significant psychiatric disorder, including the following: a.Psychiatric conditions, including but not limited to depression, bipolar disorder, schizophrenia or schizoaffective disorder that are not effectively controlled on medication and may have an adverse impact on study compliance. Symptoms including hallucinations, delusions and psychosis are exlcusionary. b.Increased risk of suicide based on the Investigator’s judgment or the results of the Columbia–Suicide Severity Rating Scale (C-SSRS) conducted at screening and Week 6 (eg, C-SSRS Type 3, 4, or 5 ideation within the past 6 months or any suicidal behavior within the past 12 months) c.HADS score >12 for either depression or anxiety at screening or Week 6 9. Has clinically significant abnormal ECG or clinical laboratory results. 10. Routinely works overnight shifts 11. Subjects with travel plans/work schedules that result in significant and frequent changes in time zones (>2 hours) will require Medical Monitor approval for enrollment 12.Females who are pregnant or nursing 13.Use of any other investigational drug from 30 days or 5 half-lives (whichever is longer) before screening to the end of the study 14.Use of the following drugs from 30 days or 5 half-lives (whichever is longer) before Day 1 to the end of the study a.rosiglitazone, aromatase inhibitors, testosterone, or growth hormones or any other medication or supplement that could impact subject safety or confound interpretation of study results b.drugs listed in section 13.1 15.Donation or receipt of blood from 90 days before Screening to the end of the study; donation or receipt of platelets, white blood cells, or plasma from 30 days before Screening to the end of the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in A4 after 12 weeks on treatment (Week 18) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Subjects blood will be collected at Baseline and Week 18. |
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E.5.2 | Secondary end point(s) |
Proportion of subjects who achieve: • A4 ≤ ULN after 12 weeks on treatment (Week 18) •17-OHP ≤ 1200 ng/dL after 12 weeks on treatment (Week 18) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Subjects blood will be collected at Baseline and Week 18. |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
Optional Open label extension study |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Switzerland |
Australia |
Brazil |
Canada |
Korea, Republic of |
United Kingdom |
United States |
Denmark |
Estonia |
Germany |
Ireland |
Italy |
Latvia |
Lithuania |
Netherlands |
Poland |
Romania |
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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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 | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 5 |