Clinical trial NCT05299554: Long-term Safety Study of Chronocort in the Treatment of Participants with Congenital Adrenal Hyperplasia
Official title: A Phase 3 Open-Label Extension Study to Evaluate the Long-term Safety and Tolerability of Chronocort in the Treatment of Participants Aged 16 Years and Over with Congenital Adrenal Hyperplasia
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Congenital Adrenal Hyperplasia
Keywords: Extension study
Lead sponsor: Neurocrine UK Limited
Sponsor class: INDUSTRY
First posted: 2022-03-29
Enrollment: 76
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm extension study
Primary purpose: TREATMENT

Brief summary: This phase III study is an open-label extension study to be conducted at approximately 21 investigational sites across 3 countries. The study will evaluate the long-term safety and tolerability of Chronocort in participants aged 16 years and over when used as treatment for Congenital Adrenal Hyperplasia (CAH).

Detailed description: Participants in eligible countries completing one of the specified previous Chronocort studies (DIUR-006 and DIUR 014) can either continue Chronocort treatment (if the participant received Chronocort in the feeder study) or switch to Chronocort treatment (if the participant received standard glucocorticoid therapy in the feeder study) in this open-label extension study. All participants choosing to enter this extension study will have the study procedures fully explained and informed consent obtained, prior to, or at the last visit of the feeder study. Participants who agree to take part in this extension study will then undergo the final visit of the feeder study, with the assessments conducted at the final visit also providing the baseline data for this DIUR-015 extension study where relevant (note participants who are withdrawn from treatment due to titration issues in study DIUR-014 are eligible to enter at the discretion of the Investigator, as long as all DIUR-014 safety assessments and the end of study visit are completed). Once all the baseline assessments are completed, participants will be given sufficient Chronocort to use until the next visit (the study pharmacies will be supplied with Chronocort for dispensing to participants according to the Investigators' instructions).

Outcome measures in this study will be assessed versus either the 'initial study baseline' (measurements taken at the start of participation in an interventional Diurnal study, regardless of the treatment assignment in this feeder study) or the protocol-defined 'pre-Chronocort baseline' (measurements taken prior to the first dose of continuous Chronocort).

Eligibility criteria: Inclusion Criteria:

* Participants with Congenital Adrenal Hyperplasia (CAH) who have successfully completed Chronocort study DIUR-006 (sites in France and US only) or study DIUR-014.
* Participants who are capable of giving signed informed consent/assent, which includes compliance with the requirements and restrictions listed in the study's informed consent form (ICF) and in the protocol.

Exclusion Criteria:

* Participants with 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).
* Participants with a history of malignancy (other than basal cell carcinoma successfully treated \>26 weeks prior to entry into the study).
* Participants with a history of bilateral adrenalectomy.
* Participants with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study.
* Participants with a co-morbid condition requiring daily administration of a medication or consumption of any material that interferes with the metabolism of glucocorticoids.
* Participants on regular daily inhaled, topical, nasal, or oral steroids for any indication other than CAH.
* 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 3 months prior to inclusion in this study, except for another clinical study with the current formulation of Chronocort.
* Females who are pregnant or lactating.
* Participants, who in the opinion of the Investigator, will be unable to comply with the requirements of the protocol.
* Participants who routinely work night shifts and so do not sleep during the usual night-time hours.
* Participants with a body weight of 50 kg or less (Note: this exclusion criterion is only applicable for French sites).

Primary outcomes:
measure: Signs and symptoms of over-treatment [Safety and Tolerability] throughout the study.
timeFrame: Up to 32 months
measure: Signs and symptoms of under-treatment [Safety and Tolerability] throughout the study.
timeFrame: Up to 32 months.
measure: To measure signs or symptoms of under treatment [Safety and Tolerability] in terms of use of additional glucocorticoid treatment throughout the study.
timeFrame: Up to 32 months
measure: To measure signs or symptoms of under treatment [Safety and Tolerability] in terms of incidence of adrenal crises throughout the study.
timeFrame: Up to 32 months
measure: To measure the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].
timeFrame: Up to 32 months
measure: To measure the change from pre-Chronocort baseline in terms of hematology safety laboratory assessments [Safety and Tolerability].
timeFrame: Up to 32 months
measure: To measure the change from pre-Chronocort baseline in terms of clinical chemistry safety laboratory assessments [Safety and Tolerability].
timeFrame: Up to 32 months
measure: To measure the change from pre-Chronocort baseline in terms of vital signs assessments.
timeFrame: Up to 32 months
Secondary outcomes:
measure: To assess the impact of treatment on dose of steroid required - Change from pre-Chronocort baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on 17-Hydroxyprogesterone (17-OHP) levels - Change from pre-Chronocort baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on Androstenedione (A4) levels - Change from pre-Chronocort baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on menstrual regularity (recorded in a participant diary) as a marker of fertility - Change from pre-Chronocort baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on luteinising hormone (LH) levels in men as a marker of fertility - Change from pre-Chronocort baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on testosterone by sex - Change from pre-Chronocort baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on waist circumference - Change from pre-Chronocort baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on body weight - Change from pre-Chronocort baseline
timeFrame: Up to 32 months
Other outcomes:
measure: To assess the impact of treatment on the dose of steroid - Change from initial study baseline daily dose
timeFrame: Up to 32 months
measure: To assess the impact of treatment on 17-Hydroxyprogesterone (17-OHP) levels - Change from initial study baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on Androstenedione (A4) levels - Change from initial study baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on menstrual regularity (recorded in a participant diary) as a marker of fertility - Change from initial study baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on luteinising hormone (LH) levels in men as a marker of fertility - Change from initial study baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on testosterone by sex - Change from initial study baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on waist circumference - Change from initial study baseline
timeFrame: Up to 32 months
measure: To assess the impact of treatment on body weight - Change from initial study baseline
timeFrame: Up to 32 months
measure: To measure the change from pre-Chronocort baseline in Quality of Life (QoL) using the EuroQol 5-level Standardized Health Questionnaire (EQ 5D-5L™).
timeFrame: Up to 32 months
measure: To measure the change from initial study baseline in Quality of Life (QoL) using the EuroQol 5-level Standardized Health Questionnaire (EQ 5D-5L™).
timeFrame: Up to 32 months
Locations:
city: Los Angeles
country: United States
facility: Diurnal Investigational Site in California
state: California
city: Orange
country: United States
facility: Diurnal Investigational Site in California
state: California
city: Jacksonville
country: United States
facility: Diurnal Investigational Site in Florida
state: Florida
city: Iowa City
country: United States
facility: Diurnal Investigational Site in Iowa
state: Iowa
city: Bethesda
country: United States
facility: National Institutes of Health Center
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 Minnesota
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 Texas
state: Texas
city: Seattle
country: United States
facility: Diurnal Investigational Site in Washington
state: Washington
city: Milwaukee
country: United States
facility: Diurnal Investigational Site in Wisconsin
state: Wisconsin
city: Caen
country: France
facility: Diurnal Investigational Site in Caen
city: Lyon
country: France
facility: Diurnal investigational Site in Lyon
city: Paris
country: France
facility: Diurnal Investigational Site in Paris
city: Pessac
country: France
facility: Diurnal Investigational Site in Pessac
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: National Instiututes of Health Clinical Centre, Bethesda, Maryland, United States, 20892-1932
name: D Merke
role: PRINCIPAL_INVESTIGATOR
References: