Clinical trial NCT03062280: A Study of the Efficacy, Safety and Tolerability of Chronocort in Treating CAH
Official title: A Phase III Extension Study of Efficacy, Safety and Tolerability of Chronocort® in the Treatment of Congenital Adrenal Hyperplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Congenital Adrenal Hyperplasia
Keywords: Extension study
Lead sponsor: Neurocrine UK Limited
Sponsor class: INDUSTRY
First posted: 2017-02-23
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Subjects completing study DIUR-005 and those who have already completed study DIUR-003 will be offered the opportunity either to continue Chronocort® therapy or to switch from their current glucocorticoid therapy to Chronocort® in this open-label study.

Detailed description: All subjects will have a screening visit prior to the baseline assessment to allow DIUR-006 procedures to be fully explained and informed consent to be given by the subject. For subjects from DIUR-003 this screening visit will include safety blood tests. Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be not be entered into the study.

All subjects will then return for the baseline visit. For subjects entering from study DIUR-003 the full set of baseline assessments will be completed, including 2 blood samples (one at 09:00 and one at 13:00 hours) for 17-OHP and A4. For subjects entering from DIUR-005, test results from their last visit in the feeder study (Visit 4) will be used for this baseline assessment, with the 09:00 and 13:00 hour results taken from the 24-hour hormone profiles conducted at the visit. Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be withdrawn from this study.

Once the baseline assessments are completed, the subjects will be given sufficient Chronocort® to use until the next visit at Week 4. Subjects from study DIUR-005 who were previously on Chronocort® will continue on the same dose of Chronocort® that they were receiving at the end of the feeder study. Subjects from study DIUR-005 on standard therapy and subjects from study DIUR-003 will have their initial dose of Chronocort® determined using the hydrocortisone equivalent of baseline therapy.

All subjects will return to the study centre at 4, 12 and 24 weeks after starting study DIUR-006 for additional blood tests and dose titration, if necessary. Visits thereafter will take place at 6-monthly intervals. If there is a change of dose, an interim visit or phone call will be needed inbetween the 6-monthly visits.

All subjects will receive telephone calls at 3 monthly intervals, and unscheduled visits will be arranged if necessary. Subjects will also be provided with Chronocort® supplies from the study pharmacy at 3-monthly or 6-monthly intervals.

Eligibility criteria: Inclusion Criteria:

1. Subjects with CAH who have successfully completed a clinical trial with the current formulation of Chronocort®.
2. Provision of signed written informed consent.

Exclusion Criteria:

1. Co-morbid condition requiring daily administration of a medication (or use of any medications/supplements) that interferes with the metabolism of glucocorticoids.
2. Clinical or biochemical evidence of hepatic or renal disease. Creatinine over twice the ULN or elevated liver function tests (ALT or AST \>2 times ULN\]).
3. Females who are pregnant or lactating.
4. Subjects on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH.
5. History of malignancy (other than basal cell carcinoma successfully treated \>6 months prior to entry into the study).
6. Subjects with a history of bilateral adrenalectomy.
7. Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study, except for another clinical trial with the current formulation of Chronocort®.
8. Subjects unable to comply with the requirements of the protocol.
9. Subjects who routinely work night shifts and so do not sleep during the usual nighttime hours.

Primary outcomes:
measure: Safety and Tolerability - Number of Participants With Adrenal Insufficiency
timeFrame: Up to approximately 5 years and 11 months
measure: Safety and Tolerability - Number of Participants Who Used Sick Day Medication
timeFrame: Up to approximately 5 years and 11 months
measure: Safety and Tolerability - Number of Participants Who Experienced at Least One Adrenal Crisis
timeFrame: Up to approximately 5 years and 11 months
measure: Safety and Tolerability - Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 5 years and 11 months
measure: Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values
timeFrame: Baseline up to approximately 5 years and 11 months
measure: Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values
timeFrame: Baseline up to approximately 5 years and 11 months
measure: Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Diastolic Blood Pressure
timeFrame: Baseline, Month 30
measure: Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Systolic Blood Pressure
timeFrame: Baseline, Month 30
measure: Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Pulse Rate
timeFrame: Baseline, Month 30
measure: Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Respiratory Rate
timeFrame: Baseline, Month 30
measure: Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Temperature
timeFrame: Baseline, Month 30
measure: Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Weight
timeFrame: Baseline, Month 30
measure: Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - BMI
timeFrame: Baseline, Month 30
measure: Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Waist Circumference
timeFrame: Baseline, Month 30
Secondary outcomes:
measure: Total Daily Dose of Chronocort in Milligrams (mg)/Day of Hydrocortisone During the Time Interval Baseline to Week 4 and Month 18 to Month 24
timeFrame: Baseline to Week 4 and Month 18-24
measure: Total Daily Dose of Chronocort in mg/Day/m^2 of Hydrocortisone by BSA During the Time Interval Baseline to Week 4 and Month 18 to Month 24
timeFrame: Baseline to Week 4 and Month 18-24
measure: Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP)
timeFrame: Baseline and Week 24
measure: Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4)
timeFrame: Baseline and Week 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - C-Terminal Cross-linked Telopeptide (CTX)
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Fasting Insulin
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Fasting Glucose
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Glycated Hemoglobin (HbA1c)
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in High Sensitivity C-reactive Protein (hsCRP)
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Plasma Renin Activity (PRA)
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Lean Mass
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Bone Mineral Density
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Fat Mass
timeFrame: Baseline, Month 24
measure: Change From Pre-Chronocort Baseline in Quality of Life - Medical Outcome Short Form Health Survey Form 36 (SF-36) Score at Months 12 and 18
timeFrame: Baseline, Months 12 and 18
measure: Change From Pre-Chronocort Baseline in Quality of Life - Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI) Score at Months 12 and 18
timeFrame: Baseline, Months 12 and 18
measure: Change From Pre-Chronocort Baseline in Quality of Life - Standardized Health Questionnaire 5-Dimension (EQ-5D) Index Score and Visual Analogue Scale (VAS) Score at Months 12 and 18
timeFrame: Baseline, Months 12 and 18
measure: Number of Participants With Dose Titrations
timeFrame: Baseline to Week 4 and Month 18
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: Neurocrine UK Limited
name: Principal Investigator
role: PRINCIPAL_INVESTIGATOR
References:
citation: Merke DP, Mallappa A, Arlt W, Brac de la Perriere A, Linden Hirschberg A, Juul A, Newell-Price J, Perry CG, Prete A, Rees DA, Reisch N, Stikkelbroeck N, Touraine P, Maltby K, Treasure FP, Porter J, Ross RJ. Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2063-e2077. doi: 10.1210/clinem/dgab051.