Open-label Comparison of Chronocort® Versus Standard Glucocorticoid Replacement Therapy

NCT03532022 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: DIUR-007
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, randomised, titration-blinded, parallel arm, multicenter study to compare twice daily Chronocort® with standard care in participants with Congenital Adrenal Hyperplasia (CAH). This study will be conducted in the USA.

Conditions

Congenital Adrenal Hyperplasia

Outcome Measures

Primary Outcomes (1)

• Non-inferiority of Chronocort® versus standard care in terms of responder rate.

  The proportion of participants after 52 weeks of treatment in the Chronocort® and standard care treatment groups achieving biochemical control. Participants with 17 OHP and A4 in the optimal (for 17-OHP) and reference range (for A4) at both timepoints of 09:00 and 13:00 hours will be classified as 'in biochemical control'; if at least one of these measurements is outside of the optimal (for 17-OHP) or reference range (for A4) they will be classified as 'not in biochemical control'.

  52 weeks

Secondary Outcomes (33)

• Impact of both treatments on markers of fertility.

  Weeks 26 & 52

• Impact of both treatments on hirsutism in female participants.

  Weeks 26 & 52

• Impact of both treatments on acne.

  Weeks 26 & 52

• Impact of both treatments on glycated hemoglobin (HbA1c) levels.

  Weeks 26 & 52

• Impact of both treatments on waist circumference (in centimetres).

  Weeks 26 & 52

Study Arms (2)

Chronocort

EXPERIMENTAL

Hydrocortisone modified release capsules - Chronocort®. 66 subjects will be randomised to this group using an interactive web response system (IWRS).

Drug: Chronocort®

Standard Care

ACTIVE COMPARATOR

Subjects participating in this arm will continue to receive their normal, standard care (hydrocortisone, dexamethasone, prednisone, prednisolone) once enrolled on the study. 66 subjects will be randomised to this arm using an interactive web response system (IWRS).

Drug: Standard Care

Interventions

Chronocort® DRUG

Hydrocortisone modified release capsules - 5mg, 10mg and 20mg.

Also known as: Hydrocortisone modified release capsules

Chronocort

Standard Care DRUG

The subject's standard care regimen upon entering the study; this could consist of hydrocortisone, dexamethasone, prednisone or prednisolone.

Also known as: Hydrocortisone, Dexamethasone, Prednisone, Prednisolone

Standard Care

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:

• Age
• Participant must be aged 16 years or older at the time of signing the informed consent.
• In participants aged \<18 years, height velocity must be less than 2 cm in the last year and puberty must be completed.
• Type of Participant and Disease Characteristics
• Participants with known CAH due to 21-hydroxylase deficiency (classic CAH) diagnosed in childhood with documented (at any time) elevated 17-OHP or A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids).
• Sex
• Male and female participants
• Male participants:
• \- A male participant must agree to use contraception as detailed in Section 10.4 of this protocol during the treatment period and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant (Section 10.4), not breastfeeding, and at least one of the following conditions applies:
• i. Not a woman of childbearing potential (WOCBP) as defined in Section 10.4. OR ii. A WOCBP with a negative pregnancy test at entry into the study who agrees to follow the contraceptive guidance in Section 10.4 during the treatment period.
• Note: females presenting with oligomenorrhea or amenorrhea who are aged ≤55 years should be considered potentially fertile and therefore, as well as undergoing pregnancy testing like all other female participants, will be expected to be using an acceptable method of contraception which should have been ongoing for ≥90 days prior to the study.
• Informed Consent
• Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• Medical Conditions
• 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 any participant who is receiving insulin.
• Participants with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study.
• Prior/Concomitant Therapy
• Participants on regular daily oral steroids for any indication other than CAH. Note: a participant should not be given any steroids (even on an irregular basis) within 5 days of a study visit. If there is a medical need for steroid treatment within this time frame then the visit should be postponed until a 5-day interval has elapsed.
• Co-morbid condition requiring daily administration of a medication or consumption of any material that interferes with the metabolism of glucocorticoids (examples provided at http://medicine.iupui.edu/clinpharm/ddis/clinical-table/).
• Participants who are receiving \<10 mg hydrocortisone dose at baseline or the hydrocortisone dose equivalent.
• Prior/Concurrent Clinical Study Experience
• Participation in another clinical study of an investigational or licensed drug or device within the 12 weeks prior to screening or during the study.
• Participants who have previously been exposed to Chronocort in studies DIUR-003, DIUR-005 or DIUR-006.
• Participants who routinely work night shifts and so do not sleep during the usual night-time hours.
• Participants unable to comply with the requirements of the protocol.

Sponsors & Collaborators

• Neurocrine UK Limited: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Diabetes and Endocrinology Consultants PC

Morehead City, North Carolina, 28557, United States

Location

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital

Interventions

Standard of Care; Hydrocortisone; Dexamethasone; Prednisone; Prednisolone

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)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Pregnadienetriols; Pregnadienes; Steroids, Fluorinated; Pregnadienediols

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: May 22, 2018
• Study Start: October 4, 2018
• Primary Completion: October 17, 2018
• Study Completion: July 9, 2021
• Last Updated: April 8, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)