Chronocort for Congenital Adrenal Hyperplasia

Enrolling by invitation at 21 trial locations

Overseen By Diurnal Information Line

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Neurocrine UK Limited

Must be taking: Chronocort

Must not be taking: Steroids, others

Disqualifiers: Hepatic disease, Renal disease, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and tolerability of Chronocort, a modified-release hydrocortisone capsule, for individuals with Congenital Adrenal Hyperplasia (CAH). CAH affects hormone production, and the trial aims to determine if Chronocort can manage it long-term. Participants must have completed a specific Chronocort study and should not have certain health issues, such as liver or kidney disease. Those with CAH who meet these criteria may find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for CAH.

Will I have to stop taking my current medications?

The trial requires that participants do not take medications that interfere with glucocorticoid metabolism or regular daily steroids for conditions other than CAH. If you are on such medications, you may need to stop them to participate.

Is there any evidence suggesting that Chronocort is likely to be safe for humans?

Research shows that Chronocort, a special form of hydrocortisone, is generally safe for people with Congenital Adrenal Hyperplasia (CAH). Studies have found that it helps manage the condition and allows for a reduction in the steroid dose over time, indicating improved safety. Long-term data from a study with 91 patients showed that Chronocort was safe and effective when used as directed. Another study confirmed that patients who completed earlier trials with Chronocort did not experience major safety issues. Overall, current evidence suggests the treatment is safe for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Congenital Adrenal Hyperplasia?

Chronocort is unique because it offers a modified-release form of hydrocortisone, which is designed to better mimic the body’s natural hormone rhythms. Standard treatments for congenital adrenal hyperplasia often involve immediate-release hydrocortisone, which can lead to fluctuations in hormone levels and less optimal control of symptoms. Chronocort’s modified-release capsules aim to provide more consistent hormone levels throughout the day, potentially improving symptom management and quality of life for patients. Researchers are excited about this treatment because it could offer a more physiological approach to hormone replacement therapy, aligning closer with the body’s needs.

What evidence suggests that Chronocort might be an effective treatment for Congenital Adrenal Hyperplasia?

Research has shown that Chronocort, a special type of hydrocortisone capsule, effectively treats congenital adrenal hyperplasia (CAH). Studies have found that it manages hormone levels more effectively and allows for a stable, lower dose of hydrocortisone over time. Patients using Chronocort have reported better control of symptoms such as excess male hormones. Additionally, Chronocort helps achieve a more natural morning cortisol level, important for feeling well-rested and energized. These findings suggest Chronocort is a promising treatment option for managing CAH. ^{3 4 6 7 8}

Who Is on the Research Team?

D Merke

Principal Investigator

National Instiututes of Health Clinical Centre, Bethesda, Maryland, United States, 20892-1932

Are You a Good Fit for This Trial?

This trial is for individuals over 16 with Congenital Adrenal Hyperplasia (CAH) who've completed previous Chronocort studies. They must be able to consent and not have conditions that interfere with the study or glucocorticoid metabolism, no recent participation in other drug trials, not pregnant/lactating, and without severe liver/renal disease.

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

I can sign and agree to follow the study's rules.

Exclusion Criteria

Participants who routinely work night shifts and so do not sleep during the usual night-time hours

My body weight is 50 kg or less.

Participants with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Extension

Participants continue or switch to Chronocort treatment for long-term safety and tolerability assessment

Up to 32 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Chronocort

Trial Overview The trial is testing the long-term safety of a medication called Chronocort for treating CAH. It's an open-label extension study across multiple countries where participants will continue using Chronocort to assess its ongoing safety profile.

How Is the Trial Designed?

Group I: Chronocort (hydrocortisone modified-release capsule) Experimental Treatment 1 Intervention

Chronocort (hydrocortisone modified-release capsules) supplied as 5 mg and 10 mg per capsule for oral administration.

Who Is Running the Clinical Trial?

Neurocrine UK Limited

Lead Sponsor

Trials

19

Recruited

710+

Diurnal Limited

Lead Sponsor

Trials

19

Recruited

710+

Published Research Related to This Trial

Modified-release hydrocortisone (MR-HC) provides a more physiological cortisol profile compared to conventional hydrocortisone (HC), with lower cortisol levels in the afternoon and night, which may improve treatment for congenital adrenal hyperplasia (CAH).

In a study of 14 patients, MR-HC resulted in better control of overnight adrenal androgens, but showed increased afternoon levels of certain hormones, indicating that a morning dose may be necessary for optimal management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (Chronocort) vs. conventional hydrocortisone (Cortef) in the treatment of congenital adrenal hyperplasia. Verma, S., Vanryzin, C., Sinaii, N., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40576296/

Long-term outcomes in patients with congenital adrenal ... Conclusions: Modified-release hard capsule treatment resulted in hydrocortisone dose reduction followed by a stable dose with improved ...

2. academic.oup.com academic.oup.com/ejendo/article/193/1/76/8165922

Long-term outcomes in patients with congenital adrenal ... Hydrocortisone modified-release hard capsules have been shown in a randomized controlled study to improve the biochemical control of congenital adrenal ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5393506/

A Phase 2 Study of Chronocort, a Modified-Release ... This novel hydrocortisone formulation was well tolerated and effective in controlling androgen excess in adults with CAH when administered twice daily.

4. prnewswire.com prnewswire.com/news-releases/neurocrine-biosciences-presented-baseline-data-from-the-cahtalyst-program-in-cah-and-study-data-for-modified-release-hydrocortisone-in-primary-adrenal-insufficiency-and-cah-at-ece-2024-302144009.html

Neurocrine Biosciences Presented Baseline Data from the ... "Treatment with modified-release hydrocortisone resulted in a greater proportion of patients with a physiological morning cortisol level than ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05063994

Study Details | NCT05063994 | Comparison of Chronocort ... The study will compare the efficacy, safety and tolerability of twice daily Chronocort with twice daily immediate release hydrocortisone replacement therapy ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33527139/

Modified-Release Hydrocortisone in Congenital Adrenal ... MR-HC improved biochemical disease control in adults with reduction in steroid dose over time and patient-reported benefit.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03062280

NCT03062280 | A Study of the Efficacy, Safety and ... Subjects with CAH who have successfully completed a clinical trial with the current formulation of Chronocort®. Provision of signed written informed consent.

8. neurocrine.gcs-web.com neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-present-phase-3-baseline-characteristics

Release Details - Neurocrine Biosciences The CHAMPAIN Phase 2 clinical study compared the efficacy, safety and tolerability of twice daily DNL0200 (Chronocort), a modified-release hydrocortisone, with ...