Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia

NCT05063994 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: DIUR-014
• Study Type: interventional
• Target: 55
• Locations: 3 countries
• Sites: 21

Brief Summary

This study is a randomized, double-blind, active-controlled, phase III study of Chronocort® compared with immediate-release hydrocortisone replacement therapy in participants aged 16 years and over with Congenital Adrenal Hyperplasia.

Conditions

Congenital Adrenal Hyperplasia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Were Biochemical Responders at Week 28

  Biochemical response was defined as a participant who a) was in biochemical control at the 08:00 assessment and b) was receiving a total daily dose of hydrocortisone of not more than 25 mg if the participant was in biochemical control at baseline or not more than 30 mg if the participant was not in biochemical control at baseline. Biochemical control was defined as both a 17-OHP concentration equal to or below the upper limit for optimal control (1200 ng/dL \[36.4 nmol/L\]) and an A4 concentration equal to or below the upper limit of the reference range (150 ng/dL \[5.2 nmol/L\] for men and 200 ng/dL \[7.0 nmol/L\] for women). Assessment of efficacy at Week 28 was a composite of each participant's on-treatment visit closest in time to 28 weeks post randomization.

  Week 28

Secondary Outcomes (14)

• Percentage of Participants Who Were Dose Responders at Week 28

  Week 28

• Total Daily Dose of Hydrocortisone at Week 28

  Week 28

• Number of Participants in Biochemical Control

  Baseline and Week 28

• Change From Baseline in Mean of 08:00 and 13:00 17-OHP Levels at Week 28

  Baseline, Week 28

• Change From Baseline in Mean of 08:00 and 13:00 A4 Levels at Week 28

  Baseline, Week 28

Study Arms (2)

Chronocort

EXPERIMENTAL

Participants received Chronocort at a starting dose of 30 milligrams (mg), with dose adjustments down to 25, 20, or 15 mg based on adrenal insufficiency symptoms and androgen levels. Placebo was used for dose adjustment to maintain blinding.

Drug: Chronocort; Other: Placebo

Cortef

ACTIVE COMPARATOR

Participants received Cortef at a starting dose of 30 mg, with dose adjustments down to 25, 20, or 15 mg based on adrenal insufficiency symptoms and androgen levels. Placebo was used for dose adjustment to maintain blinding.

Drug: Cortef; Other: Placebo

Interventions

Chronocort DRUG

Over-encapsulated hydrocortisone modified-release capsule for oral administration.

Also known as: Hydrocortisone modified-release

Chronocort

Cortef DRUG

Over-encapsulated hydrocortisone immediate-release tablet for oral administration.

Also known as: Immediate-release hydrocortisone, IRHC

Cortef

Placebo OTHER

Matching placebo

Chronocort; Cortef

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants must be aged 16 years or older at the time of signing the informed consent/assent.
• In participants aged \<18 years, height velocity must be less than 2 cm/year in the last year and puberty must be completed (Tanner stage V).
• Participants with known classic CAH due to 21 hydroxylase deficiency diagnosed in childhood with documented (at any time) elevated 17-OHP and with or without elevated A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids) and on stable glucocorticoid therapy for a minimum of 3 months.
• Participants who are receiving fludrocortisone must be on a documented stable dose for a minimum of 3 months prior to enrollment and must have stable renin levels at screening.
• Female participants of childbearing potential and all male participants must agree to the use of an accepted method of contraception during the study.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and she is either not a woman of childbearing potential (WOCBP) or has a negative pregnancy test at entry into the study. Note: females presenting with oligomenorrhea or amenorrhea who are aged ≤55 years should be considered potentially fertile and therefore should undergo pregnancy testing like all other female participants.
• Capable of giving signed informed consent/assent which includes compliance with requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• Clinical or biochemical evidence of hepatic or renal disease e.g. creatinine \>2 times the upper limit of normal (ULN) or elevated liver function tests (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \>2 times the ULN).
• History of bilateral adrenalectomy.
• History of malignancy (other than basal cell carcinoma successfully treated \>26 weeks prior to entry into the study).
• Participants who have type 1 diabetes or receive regular insulin, have uncontrolled diabetes, or have a screening HbA1c greater than 8%.
• Persistent signs of adrenal insufficiency or the participant does not tolerate treatment at the end of the 4-week run-in period.
• Participants with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study.
• Participants on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH.
• Co-morbid condition requiring daily administration of a medication or consumption of any material that interferes with the metabolism of glucocorticoids.
• Participants who are receiving \<10 mg hydrocortisone dose at screening or the hydrocortisone dose equivalent.
• Participants anticipating regular prophylactic use of additional steroids e.g. for strenuous exercise.
• Participation in another clinical study of an investigational or licensed drug or device within the 12 weeks prior to screening.
• Participants who have previously been exposed to Chronocort in any Diurnal study.
• Participants who routinely work night shifts and so do not sleep during the usual night-time hours.
• Participants, who in the opinion of the Investigator, will be unable to comply with the requirements of the protocol.
• Participants with a known hypersensitivity to any of the components of the Chronocort capsules, the Cortef tablets, or the placebo capsules.

Sponsors & Collaborators

• Neurocrine UK Limited: lead

Study Sites (21)

Diurnal Investigational Site in Los Angeles

Los Angeles, California, 90027, United States

Location

Diurnal Investigational Site in Orange

Orange, California, 92868, United States

Location

Diurnal Investigational Site in Jacksonville

Jacksonville, Florida, 32207, United States

Location

Diurnal Investigational Site in Iowa

Iowa City, Iowa, 52224, United States

Location

Diurnal Investigational Site in Maryland

Bethesda, Maryland, 20892-1932, United States

Location

Diurnal Investigational Site in Michigan

Ann Arbor, Michigan, 48109, United States

Location

Diurnal Investigational Site in Rochester

Rochester, Minnesota, 55901, United States

Location

Diurnal Investigational Site in Nevada

Las Vegas, Nevada, 89148, United States

Location

Diurnal Investigational Site in Dallas

Dallas, Texas, 75235, United States

Location

Diurnal Investigational Site in Seattle

Seattle, Washington, 98105, United States

Location

Diurnal Investigational Site in Milwaukee

Milwaukee, Wisconsin, 53226, United States

Location

Diurnal Investigational Site in Caen

Caen, Normandy, 14033, France

Location

Diurnal Investigational Site in Pessac

Bordeaux, 33604, France

Location

Diurnal Investigational Site in Bron

Lyon, 69677, France

Location

Diurnal Investigational Site in Paris

Paris, 75651, France

Location

Diurnal Investigational Site in Toulouse (Children's Hospital)

Toulouse, 31059, France

Location

Diurnal Investigational Site in Toulouse

Toulouse, 31059, France

Location

Diurnal Investigational Site in Asahi-ku

Yokohama, Kanagawa, 241-0811, Japan

Location

Diurnal Investigational Site in Yushima

Bunkyō-Ku, Tokyo, 113-8519, Japan

Location

Diurnal Investigational Site in Okura

Setagaya-Ku, Tokyo, 157-8535, Japan

Location

Diurnal Investigational Site in Toyama

Shinjuku-Ku, Tokyo, 162-8655, Japan

Location

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Clinical Trials Information
• Organization: Diurnal Limited

info@diurnal.co.uk

+44 (0) 292 068 2069

Study Officials

• Principal Investigator

  Neurocrine UK Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: October 1, 2021
• Study Start: May 24, 2022
• Primary Completion: February 2, 2024
• Study Completion: February 2, 2024
• Last Updated: February 25, 2025
• Results First Posted: February 24, 2025

Record last verified: 2025-02

Locations

JP (4); US (11); FR (6)