Chronocort vs Standard Therapy for Congenital Adrenal Hyperplasia

(CONnECT Trial)

Recruiting at 31 trial locations

Overseen By Diurnal Information Line

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Neurocrine UK Limited

Must be taking: Glucocorticoids

Must not be taking: Regular steroids

Disqualifiers: Hepatic disease, Renal disease, Diabetes, 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: 4

Duration: 28 weeks

55 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares Chronocort®, a slow-releasing cortisol medication, with another form of cortisol treatment in people aged 16 and over who have Congenital Adrenal Hyperplasia (CAH). CAH patients need hormone replacement because their bodies can't produce enough cortisol. Chronocort® aims to provide a more stable hormone level throughout the day. Chronocort is a modified-release hydrocortisone developed to replace the cortisol rhythm in patients with congenital adrenal hyperplasia.

Will I have to stop taking my current medications?

The trial requires participants to be on stable glucocorticoid therapy for at least 3 months before joining, so you won't need to stop taking your current glucocorticoid medications. However, if you are on other steroids for conditions besides CAH, you may need to stop those.

What data supports the effectiveness of the drug Chronocort for treating congenital adrenal hyperplasia?

Research comparing Chronocort to conventional hydrocortisone (Cortef) shows that Chronocort, a modified-release hydrocortisone, may offer better control of hormone levels in patients with congenital adrenal hyperplasia, potentially leading to more stable treatment outcomes. ^{1 2 3 4 5}

How does the drug Chronocort differ from standard treatments for congenital adrenal hyperplasia?

Chronocort is a modified-release form of hydrocortisone designed to better mimic the body's natural cortisol rhythm, unlike standard treatments that do not replicate this pattern, potentially leading to more stable hormone levels and fewer side effects. ^{2 4 6 7 8}

Research Team

Principal Investigator

Principal Investigator

Neurocrine UK Limited

Eligibility Criteria

This trial is for individuals over 16 with classic Congenital Adrenal Hyperplasia (CAH) treated with certain steroids for at least 3 months. They must not be pregnant, breastfeeding, or planning to become pregnant and agree to use contraception. Exclusions include previous Chronocort exposure, weight under 45 kg, night shift workers, certain medical conditions including uncontrolled diabetes, and those on other steroid treatments.

Inclusion Criteria

You have been diagnosed with a specific hormone deficiency called classic CAH since childhood and are currently taking certain medications for it.

A female participant is eligible to participate if she is not pregnant, not breastfeeding, and she is either not a woman of childbearing potential (WOCBP) or has a negative pregnancy test at entry into the study. Note: females presenting with oligomenorrhea or amenorrhea who are aged ≤55 years should be considered potentially fertile and therefore should undergo pregnancy testing like all other female participants.

Male or female participants must be aged 16 years or older at the time of signing the informed consent/assent.

Exclusion Criteria

You are taking steroids every day for reasons other than a specific condition called CAH.

Participants who have previously been exposed to Chronocort in any Diurnal study.

You weigh 45 kilograms or less.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Chronocort or immediate-release hydrocortisone replacement therapy for 28 weeks

28 weeks

Visits at baseline, 4, 10, 16, and 28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Chronocort
• Cortef

Trial Overview The study compares Chronocort®, a new therapy for CAH, against the standard immediate-release hydrocortisone (Cortef). It's a phase III trial where participants are randomly assigned to either treatment without knowing which one they receive (double-blind) to evaluate effectiveness and safety.

Participant Groups

Group I: Chronocort Experimental Treatment 2 Interventions

Participants received Chronocort at a starting dose of 30 milligrams (mg), with dose adjustments down to 25, 20, or 15 mg based on adrenal insufficiency symptoms and androgen levels. Placebo was used for dose adjustment to maintain blinding.

Group II: Cortef Active Control 2 Interventions

Participants received Cortef at a starting dose of 30 mg, with dose adjustments down to 25, 20, or 15 mg based on adrenal insufficiency symptoms and androgen levels. Placebo was used for dose adjustment to maintain blinding.

Who Is Running the Clinical Trial?

Neurocrine UK Limited

Lead Sponsor

Trials

19

Recruited

710+

Diurnal Limited

Lead Sponsor

Trials

19

Recruited

710+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers. [2022]

2. England 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. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Growth patterns and outcomes in congenital adrenal hyperplasia; effect of chronic treatment regimens. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Emerging medical therapies for congenital adrenal hyperplasia. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Subjective health status in men and women with congenital adrenal hyperplasia: a population-based survey in Norway. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Substitution therapy in adult patients with congenital adrenal hyperplasia. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Monitoring treatment in congenital adrenal hyperplasia. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

[Treatment of adult men with congenital adrenal hyperplasia syndrome due to 21-hydroxylase deficiency]. [2016]