Long-term Safety Study of Chronocort in the Treatment of Participants With Congenital Adrenal Hyperplasia

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

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).

Study Overview

• Status: Enrolling by invitation
• Conditions: Congenital Adrenal Hyperplasia
• Intervention / Treatment: Drug: Chronocort

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visit also providing the baseline data for this DIUR-015 extension study where relevant (note participants who are withdrawn from treatment due to titration issues in study DIUR-014 are eligible to enter at the discretion of the Investigator, as long as all DIUR-014 safety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).

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Caen, France, 14033
    • Diurnal Investigational Site in Caen
  • Lyon, France, 69677
    • Diurnal investigational Site in Lyon
  • Paris, France, 75651
    • Diurnal Investigational Site in Paris
  • Pessac, France, 33604
    • Diurnal Investigational Site in Pessac
  • Toulouse, France, 31059
    • Diurnal Investigational Site in Toulouse (Children's hospital)
  • Toulouse, France, 31059
    • Diurnal Investigational Site in Toulouse
• Japan
  • Kanagawa
    • Yokohama-shi, Kanagawa, Japan, 241-0811
      • Diurnal Investigational Site in Asahi-ku
  • Tokyo
    • Bunkyō-Ku, Tokyo, Japan, 113-8519
      • Diurnal Investigational Site in Yushima
    • Setagaya-Ku, Tokyo, Japan, 157-8535
      • Diurnal Investigational Site in Okura
    • Shinjuku-Ku, Tokyo, Japan, 162-8655
      • Diurnal Investigational Site in Toyama
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Diurnal Investigational Site in California
    • Orange, California, United States, 92868
      • Diurnal Investigational Site in California
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Diurnal Investigational Site in Florida
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Diurnal Investigational Site in Iowa
  • Maryland
    • Bethesda, Maryland, United States, 20892-1932
      • National Institutes of Health Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48114
      • Diurnal Investigational Site in Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55901
      • Diurnal Investigational Site in Minnesota
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Diurnal Investigational Site in Nevada
  • Texas
    • Dallas, Texas, United States, 75235
      • Diurnal Investigational Site in Texas
  • Washington
    • Seattle, Washington, United States, 98105
      • Diurnal Investigational Site in Washington
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Diurnal Investigational Site in Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chronocort (hydrocortisone modified-release capsule); Chronocort (hydrocortisone modified-release capsules) supplied as 5 mg and 10 mg per capsule for oral administration.	Drug: Chronocort; Hydrocortisone modified-release capsule 5 mg and 10 mg; Other Names: Hydrocortisone modified-release hard capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signs and symptoms of over-treatment [Safety and Tolerability] throughout the study.	Over-replacement normally presents with chronic effects such as weight gain, increased appetite, sleeping difficulties, increased acne and Cushingoid syndrome.	Up to 32 months
Signs and symptoms of under-treatment [Safety and Tolerability] throughout the study.	Under-replacement normally presents with acute effects such as sudden weight loss, lack of appetite, nausea, vomiting, headache, blurred vision, fatigue, weakness, dizziness, light-headedness and syncope.	Up to 32 months.
To measure signs or symptoms of under treatment [Safety and Tolerability] in terms of use of additional glucocorticoid treatment throughout the study.	Use of Immediate Release Hydrocortisone (IRHC) from the emergency packs for stress dosing or use of any additional glucocorticoid treatment.	Up to 32 months
To measure signs or symptoms of under treatment [Safety and Tolerability] in terms of incidence of adrenal crises throughout the study.	Occurrence of adrenal crises throughout the study.	Up to 32 months
To measure the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].	The incidence, nature, severity, relatedness, duration, outcome, seriousness, and expectedness of treatment-emergent adverse events (TEAEs) throughout the study.	Up to 32 months
To measure the change from pre-Chronocort baseline in terms of hematology safety laboratory assessments [Safety and Tolerability].	Lab parameters will be summarized and compared throughout the study as follows: Platelet count, Red blood cell count (RBC), Haemoglobin, Haematocrit, RBC Indices: Mean corpuscular volume (MCV), Mean cell haemoglobin (MCH). Mean cell haemoglobin concentration (MCHC), Red cell distribution width (RDW). White blood cell (WBC) count with differential (absolute and %): Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils.	Up to 32 months
To measure the change from pre-Chronocort baseline in terms of clinical chemistry safety laboratory assessments [Safety and Tolerability].	To measure the change from pre-Chronocort baseline in terms of clinical chemistry safety laboratory assessments [Safety and Tolerability]. Blood urea nitrogen (BUN), Creatinine, Chloride, Total magnesium, Potassium, Sodium, Calcium, Total carbon dioxide (CO2), Inorganic phosphorus, AST/serum glutamic-oxaloacetic transaminase (SGOT), ALT/serum glutamic-pyruvic transaminase (SGPT), Alkaline phosphatase, Albumin, Total and direct bilirubin, Total protein, Lactate dehydrogenase (LDH), Total creatine kinase (CK), Uric acid.	Up to 32 months
To measure the change from pre-Chronocort baseline in terms of vital signs assessments.	Blood pressure measurements throughout the study will be summarised and compared.	Up to 32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact of treatment on dose of steroid required - Change from pre-Chronocort baseline	Change from pre-Chronocort baseline in total daily steroid dose in hydrocortisone equivalent dose at each visit.	Up to 32 months
To assess the impact of treatment on 17-Hydroxyprogesterone (17-OHP) levels - Change from pre-Chronocort baseline	Change in 17-OHP levels from pre Chronocort baseline at each visit.	Up to 32 months
To assess the impact of treatment on Androstenedione (A4) levels - Change from pre-Chronocort baseline	Change in A4 levels from pre-Chronocort baseline at each visit.	Up to 32 months
To assess the impact of treatment on menstrual regularity (recorded in a participant diary) as a marker of fertility - Change from pre-Chronocort baseline	Change from pre-Chronocort baseline in menstrual regularity as recorded in a participant diary. With menstrual regularity defined as a cycle (menstrual bleeding) occurring every 21 to 35 days (only in pre-menopausal females without hysterectomy and not using hormonal contraceptives).	Up to 32 months
To assess the impact of treatment on luteinising hormone (LH) levels in men as a marker of fertility - Change from pre-Chronocort baseline	Change from pre-Chronocort baseline in luteinising hormone (LH) levels throughout the study.	Up to 32 months
To assess the impact of treatment on testosterone by sex - Change from pre-Chronocort baseline	Change in testosterone levels from pre-Chronocort baseline through the study, summarized by gender.	Up to 32 months
To assess the impact of treatment on waist circumference - Change from pre-Chronocort baseline	Change from pre-Chronocort baseline to each visit in waist circumference.	Up to 32 months
To assess the impact of treatment on body weight - Change from pre-Chronocort baseline	Change from pre-Chronocort baseline to each visit in body weight.	Up to 32 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact of treatment on the dose of steroid - Change from initial study baseline daily dose	Change from initial study baseline in daily steroid dose as the hydrocortisone equivalent dose.	Up to 32 months
To assess the impact of treatment on 17-Hydroxyprogesterone (17-OHP) levels - Change from initial study baseline	Change in 17-OHP levels from initial study baseline throughout the study.	Up to 32 months
To assess the impact of treatment on Androstenedione (A4) levels - Change from initial study baseline	Change in A4 levels from initial study baseline throughout the study.	Up to 32 months
To assess the impact of treatment on menstrual regularity (recorded in a participant diary) as a marker of fertility - Change from initial study baseline	Change from initial study baseline in menstrual regularity as recorded in a participant diary. With menstrual regularity defined as a cycle (menstrual bleeding) occurring every 21 to 35 days (only in pre-menopausal females without hysterectomy and not using hormonal contraceptives).	Up to 32 months
To assess the impact of treatment on luteinising hormone (LH) levels in men as a marker of fertility - Change from initial study baseline	Change from initial study baseline on luteinising hormone (LH) levels throughout the study.	Up to 32 months
To assess the impact of treatment on testosterone by sex - Change from initial study baseline	Change in testosterone from initial study baseline throughout the study, summarized by gender.	Up to 32 months
To assess the impact of treatment on waist circumference - Change from initial study baseline	Change from initial study baseline throughout the study in waist circumference.	Up to 32 months
To assess the impact of treatment on body weight - Change from initial study baseline	Change from initial study baseline throughout the study in body weight.	Up to 32 months
To measure the change from pre-Chronocort baseline in Quality of Life (QoL) using the EuroQol 5-level Standardized Health Questionnaire (EQ 5D-5L™).	QoL will be summarized and compared throughout the study. The scale measures on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Where the minimum score is 0 and maximum score is 100, a high score indicates a more favorable outcome.	Up to 32 months
To measure the change from initial study baseline in Quality of Life (QoL) using the EuroQol 5-level Standardized Health Questionnaire (EQ 5D-5L™).	QoL will be summarized and compared throughout the study. The scale measures on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Where the minimum score is 0 and maximum score is 100, a high score indicates a more favorable outcome.	Up to 32 months

Collaborators and Investigators

• Sponsor: Diurnal Limited
• Investigators: Principal Investigator: D Merke, National Instiututes of Health Clinical Centre, Bethesda, Maryland, United States, 20892-1932

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 5, 2022
• First Submitted That Met QC Criteria: March 18, 2022
• First Posted (Actual): March 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Extension study
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction; Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: DIUR-015

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No