Chronocort vs Standard Therapy for Congenital Adrenal Hyperplasia

(CONnECT Trial)

No longer recruiting at 32 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Chronocort for individuals with Congenital Adrenal Hyperplasia (CAH), a condition affecting hormone production. Researchers aim to determine if Chronocort manages symptoms as effectively as the current standard treatment, Cortef. Participants will receive either Chronocort or Cortef, with doses adjusted based on symptoms and hormone levels. Suitable candidates for this trial are those aged 16 and older with a history of CAH diagnosed in childhood and who have maintained steady hormone treatment for at least three months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Chronocort has been tested for safety in people with Congenital Adrenal Hyperplasia (CAH). In a long-term safety study, Chronocort was used for several months and demonstrated effectiveness without causing major side effects. This indicates the treatment was effective and generally safe over time.

Participants using Chronocort in these studies rarely experienced serious problems, such as adrenal crises, which are severe health issues related to hormone imbalance. These events were tracked and found to be rare, suggesting Chronocort is generally well-tolerated.

Overall, the evidence suggests that Chronocort is a safe option for managing CAH, with patients tolerating the treatment well over a long period. ^{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 more precise way to manage congenital adrenal hyperplasia (CAH) by mimicking the body's natural cortisol rhythm. Unlike standard treatments like Cortef, which provide cortisol in a less physiological manner, Chronocort releases cortisol in a time-controlled way, which could lead to better symptom control and fewer side effects. Researchers are excited about Chronocort because it has the potential to improve patients' quality of life by providing more consistent hormone levels throughout the day.

What evidence suggests that this trial's treatments could be effective for Congenital Adrenal Hyperplasia?

Research shows that Chronocort, a special type of hydrocortisone, helps manage congenital adrenal hyperplasia (CAH). In this trial, participants will receive either Chronocort or the standard therapy, Cortef. Studies have found that Chronocort can better match the body's natural cortisol pattern, effectively controlling hormone levels related to male traits. Earlier research indicated that patients using Chronocort maintained stable hormone levels and experienced symptom improvement over time. This treatment was well tolerated, with few side effects reported. Overall, early findings suggest Chronocort may be a promising alternative to traditional hydrocortisone treatment for people with CAH. ^{4 6 7 8 9}

Who Is on the Research Team?

Principal Investigator

Principal Investigator

Neurocrine UK Limited

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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 ... Modified-release hard capsule treatment resulted in hydrocortisone dose reduction followed by a stable dose with improved biochemical ...

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

A Phase 2 Study of Chronocort, a Modified-Release ... Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This ...

3. 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 ...

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 ... Phase 3 Extension Study of Modified-Release Hydrocortisone (Chronocort®) in Congenital Adrenal Hyperplasia MRHC also demonstrated potential ...

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

Long-term outcomes in patients with congenital adrenal ... Congenital adrenal hyperplasia cohort studies in the last 20 years have shown poor health with increased mortality, height below genetic potential, reduced ...

6. 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.

7. ipgroupplc.com ipgroupplc.com/news-and-events/portfolio-news/2021/2021-02-02

Chronocort® Phase 3 and Safety Extension Study results ... In the safety extension study, biochemical control was sustained for 18 months on median hydrocortisone doses in the range recommended for ...

8. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=16-CH-0164&&query=Congenital

Protocol Details Objective: To determine the safety and effectiveness of Chronocort(R) over a maximum of 40 months. Eligibility: People with CAH who have successfully completed ...

9. clinicaltrial.be clinicaltrial.be/en/details/175854?only_active=0&only_eligible=0&only_recruiting=0&per_page=20

Long-term Safety Study of Chronocort in the Treatment of... To measure signs or symptoms of under treatment [Safety and Tolerability] in terms of incidence of adrenal crises throughout the study.