Clinical trial NCT05063994: Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia
Official title: A Randomized, Double-Blind, Active-Controlled, Phase 3 Study of Chronocort Compared With Immediate-Release Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Congenital Adrenal Hyperplasia
Lead sponsor: Neurocrine UK Limited
Sponsor class: INDUSTRY
First posted: 2021-10-01
Enrollment: 55
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The study will compare the efficacy, safety and tolerability of twice daily Chronocort with twice daily immediate release hydrocortisone replacement therapy (IRHC) (Cortef®) in participants aged 16 years and over with known classic Congenital Adrenal Hyperplasia (CAH) due to 21 hydroxylase deficiency.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Inclusion in any natural history or translational research study that would require evaluation of androgen levels during the study period outside of this protocol's assessments.
* 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.
* Participants with congenital galactosemia, malabsorption of glucose and galactose, or who are lactase deficient.
* Participants with a body weight of 45 kg or less.

Primary outcomes:
measure: Percentage of Participants Who Were Biochemical Responders at Week 28
timeFrame: Week 28
Secondary outcomes:
measure: Percentage of Participants Who Were Dose Responders at Week 28
timeFrame: Week 28
measure: Total Daily Dose of Hydrocortisone at Week 28
timeFrame: Week 28
measure: Number of Participants in Biochemical Control
timeFrame: Baseline and Week 28
measure: Change From Baseline in Mean of 08:00 and 13:00 17-OHP Levels at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Mean of 08:00 and 13:00 A4 Levels at Week 28
timeFrame: Baseline, Week 28
measure: Number of Participants With Menstrual Regularity (Females of Childbearing Potential Only) at Week 28
timeFrame: Week 28
measure: Change From Baseline in Luteinizing Hormone Levels (Males Only) at Week 28
timeFrame: Baseline, Week 28
measure: Percent Change From Baseline in Size of Testicular Adrenal Rest Tumors at Week 28 (Males Only)
timeFrame: Week 28
measure: Change From Baseline in Hirsutism at Week 28 Using the Ferriman-Gallwey Score (Females Only) at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Acne Using the Global Evaluation Acne (GEA) Scale (Females Only) at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Glycated Hemoglobin (HbA1c) Percent Levels at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Waist Circumference at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Body Weight at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline Quality of Life Using the Self-completed Medical Outcome Study 36-Item Short Form Health Survey (SF-36) Total Score for the Physical and Mental Components and the Sub-domain of Vitality at Week 28
timeFrame: Baseline, Week 28
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Diurnal Investigational Site in Los Angeles
state: California
city: Orange
country: United States
facility: Diurnal Investigational Site in Orange
state: California
city: Jacksonville
country: United States
facility: Diurnal Investigational Site in Jacksonville
state: Florida
city: Iowa City
country: United States
facility: Diurnal Investigational Site in Iowa
state: Iowa
city: Bethesda
country: United States
facility: Diurnal Investigational Site in Maryland
state: Maryland
city: Ann Arbor
country: United States
facility: Diurnal Investigational Site in Michigan
state: Michigan
city: Rochester
country: United States
facility: Diurnal Investigational Site in Rochester
state: Minnesota
city: Las Vegas
country: United States
facility: Diurnal Investigational Site in Nevada
state: Nevada
city: Dallas
country: United States
facility: Diurnal Investigational Site in Dallas
state: Texas
city: Seattle
country: United States
facility: Diurnal Investigational Site in Seattle
state: Washington
city: Milwaukee
country: United States
facility: Diurnal Investigational Site in Milwaukee
state: Wisconsin
city: Caen
country: France
facility: Diurnal Investigational Site in Caen
state: Normandy
city: Bordeaux
country: France
facility: Diurnal Investigational Site in Pessac
city: Lyon
country: France
facility: Diurnal Investigational Site in Bron
city: Paris
country: France
facility: Diurnal Investigational Site in Paris
city: Toulouse
country: France
facility: Diurnal Investigational Site in Toulouse (Children's Hospital)
city: Toulouse
country: France
facility: Diurnal Investigational Site in Toulouse
city: Yokohama-shi
country: Japan
facility: Diurnal Investigational Site in Asahi-ku
state: Kanagawa
city: Bunkyō-Ku
country: Japan
facility: Diurnal Investigational Site in Yushima
state: Tokyo
city: Setagaya-Ku
country: Japan
facility: Diurnal Investigational Site in Okura
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Diurnal Investigational Site in Toyama
state: Tokyo
Study officials:
affiliation: Neurocrine UK Limited
name: Principal Investigator
role: PRINCIPAL_INVESTIGATOR
References: