What side effects are associated with this type of intervention?

Treatments for Congenital Adrenal Hyperplasia (CAH), such as hydrocortisone and other glucocorticoids, can have several side effects. These include weight gain, impaired glucose tolerance, increased risk of infections, and potential impacts on bone density like osteoporosis. Long-term use may also lead to growth suppression in children and adolescents. These side effects are crucial considerations in the management of CAH.

What prior FDA approvals exist?

The FDA has approved various formulations of hydrocortisone for the treatment of Congenital Adrenal Hyperplasia (CAH). Standard immediate-release hydrocortisone has been a mainstay in managing CAH to replace deficient cortisol. Chronocort® represents a newer, sustained-release formulation of hydrocortisone designed to provide more stable cortisol levels throughout the day, potentially improving disease management and patient outcomes. Other related treatments include fludrocortisone, which is often used in conjunction with hydrocortisone to address aldosterone deficiency in CAH patients.

What other types of research exist?

Promising novel alternatives to Chronocort® for CAH patients include postnatal soluble FGFR3 therapy, which has shown potential in rescuing symptoms and restoring bone growth in preclinical studies. Additionally, advancements in gene therapy and other targeted molecular therapies are being explored and may offer new treatment avenues in the near future.

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Corticosteroid

Chronocort vs Standard Therapy for Congenital Adrenal Hyperplasia (CONnECT Trial)

Phase 3

Waitlist Available

Led By D Merke

Research Sponsored by Diurnal Limited

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

In participants aged <18 years, height velocity must be less than 2 cm/year in the last year and puberty must be completed (Tanner stage V).

Must not have

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.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 weeks (assessed at baseline, 4, 10, 16 and 28 weeks)

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects aren't listed here, both Chronocort® and Cortef can cause symptoms related to hormone imbalance such as fatigue, mood changes or skin issues. Side effects may also include signs of too much or too little steroid effect like swelling or weight gain.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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If you are under 18, you must have grown less than 2 centimeters in the last year and have finished going through puberty.

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If you take fludrocortisone, you must have been taking the same amount for at least 3 months before joining the study, and your renin levels must be stable.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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You have liver or kidney problems, as shown by certain blood tests being higher than normal.

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You have had surgery to remove both adrenal glands.

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You have type 1 diabetes, uncontrolled diabetes, or a high HbA1c level.

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

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You have a medical condition that requires you to take a medication every day, or consume something that affects how your body processes glucocorticoids.

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You are taking less than 10 mg of hydrocortisone or a similar medication at the time of screening.

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You work at night and don't sleep during regular nighttime hours.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 weeks (assessed at baseline, 4, 10, 16 and 28 weeks)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 weeks (assessed at baseline, 4, 10, 16 and 28 weeks)

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 weeks (assessed at baseline, 4, 10, 16 and 28 weeks) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To compare Chronocort to IRHC in terms of biochemical responder rate after 28 weeks of randomized treatment - 17-OHP concentration

To compare Chronocort to IRHC in terms of biochemical responder rate after 28 weeks of randomized treatment - A4 concentration

To compare Chronocort to IRHC in terms of biochemical responder rate after 28 weeks of randomized treatment - Total daily dose of Hydrocortisone

Secondary study objectives

To assess compliance over the study period.

To compare Chronocort to IRHC in terms of biochemical control at 10, 16, and 28 weeks after randomization.

To compare Chronocort to IRHC in terms of biochemical responders at 4, 10, 16, and 28 weeks after randomization.

+25 more

Other study objectives

To assess dose changes over the study period - Change in mg

To assess dose changes over the study period - Incidence

To assess preference for treatment.

+28 more

Side effects data

From 2009 Phase 1 & 2 trial • 20 Patients • NCT00519818

21%

Headache

100%

80%

60%

40%

20%

Study treatment Arm

Cortef

Chronocort

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: ChronocortExperimental Treatment1 Intervention

Hydrocortisone modified-release capsule - Chronocort®. 25 subjects will be randomised to this group using an interactive response technology (IRT).

Group II: CortefActive Control1 Intervention

Immediate-release hydrocortisone capsule (IRHC) - Cortef. 25 subjects will be randomised to this group using an interactive response technology (IRT).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Chronocort

2021

Completed Phase 3

~200

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Congenital Adrenal Hyperplasia (CAH) involve glucocorticoid replacement therapy, such as hydrocortisone, to manage cortisol deficiency. Hydrocortisone works by mimicking the natural cortisol hormone, helping to regulate metabolism, immune response, and stress. Chronocort®, a sustained release form of hydrocortisone, provides a more stable and prolonged release of the hormone, which is crucial for maintaining consistent cortisol levels and reducing the risk of adrenal crises. This is particularly important for CAH patients, as it helps to better manage symptoms and improve overall quality of life by preventing the peaks and troughs associated with immediate-release formulations.