A study of safety and efficacy of NBI-74788 in Classic Congenital Adrenal Hyperplasia

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2019-004873-17-NL
• Date of registration: 12/11/2020
• Prospective Registration: Yes
• Primary sponsor: Neurocrine Biosciences, Inc.
• Public title: A study of safety and efficacy of NBI-74788 in Classic Congenital Adrenal Hyperplasia
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Crinecerfont (NBI-74788) in Adult Subjects with Classic Congenital Adrenal Hyperplasia, Followed by Open-Label Treatment (CAHTALYST)
• Date of first enrolment: 20/07/2021
• Target sample size: 165
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004873-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: open-label period If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Czech Republic, Czechia, France, Germany, Greece, Israel, Italy, Netherlands, Poland, Portugal, Serbia, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Regulatory Unit
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

• Name: Regulatory Unit
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

Key inclusion & exclusion 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 (defined as >13 mg/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.
• 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.
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:
• 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Classic Congenital Adrenal Hyperplasia (CAH)
MedDRA version: 20.0 Level: LLT Classification code 10010323 Term: Congenital adrenal hyperplasia System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Intervention(s)

Product Name: Crinecerfont
Product Code: NBI-74788
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Crinecerfont
CAS Number: 752253-39-7
Current Sponsor code: NBI-74788
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

Primary end point(s): Percent change from baseline in glucocorticoid daily dose (in hydrocortisone equivalents adjusted for BSA [mg/m2/day]) at Week 24

Secondary Objective: Not applicable

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 Outcome(s)

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

Secondary ID(s)

NBI-74788-CAH3003

2019-004873-17-GB

Source(s) of Monetary Support

Neurocrine Biosciences, Inc.

Ethics review

Status: Approved
Approval date: 20/07/2021
Contact: