What is the mechanism of action of this treatment?

Common treatments for Congenital Adrenal Hyperplasia (CAH) include hydrocortisone and abiraterone acetate. Hydrocortisone replaces deficient cortisol and suppresses excess adrenal androgen production, which is crucial for preventing accelerated skeletal maturation and other androgen-related complications. Abiraterone acetate inhibits the CYP17 enzyme, directly reducing androgen production. This dual approach helps manage androgen levels more effectively while minimizing the need for high doses of hydrocortisone, thereby reducing the risk of growth retardation and other side effects associated with long-term glucocorticoid use.

What side effects are associated with this type of intervention?

Treatments for Congenital Adrenal Hyperplasia (CAH) that reduce androgen production, such as Abiraterone Acetate, commonly cause side effects including hypertension, hypokalemia, and potential liver toxicity. These therapies may also lead to adrenal insufficiency due to the suppression of adrenal androgen precursors. Regular monitoring is essential to manage these side effects effectively.

What prior FDA approvals exist?

The standard FDA-approved treatments for Congenital Adrenal Hyperplasia (CAH) primarily include glucocorticoids like hydrocortisone and mineralocorticoids like fludrocortisone to manage hormone levels and reduce androgen production. These treatments aim to replace deficient hormones and suppress excess androgen production. Abiraterone Acetate, which inhibits the CYP17 enzyme to reduce androgen production, is currently being studied as an adjunct therapy to potentially reduce the required doses of hydrocortisone in CAH patients.

What other types of research exist?

Promising novel alternatives to Abiraterone Acetate for treating Congenital Adrenal Hyperplasia in 2024 may include advanced genetic therapies and other enzyme inhibitors that target androgen production. These could involve the use of recombinant growth hormone, aromatase inhibitors like Letrozole, or emerging genetic therapies that offer more precise control over androgen levels.

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Abiraterone Acetate for Congenital Adrenal Hyperplasia

Phase 1

Waitlist Available

Led By Perrin C White, MD

Research Sponsored by University of Texas Southwestern Medical Center

Eligibility Criteria Checklist

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

Must have

Requirement for standard of care fludrocortisone (any dose) and ≥10 mg/m2/day of hydrocortisone for at least 1 month prior to the study consent

Confirmed classic 21-hydroxylase deficiency evident by genotype groups A, A1 or B or clinical course (e.g., adrenal crisis with documented hyperkalemia and hyponatremia, at diagnosis or during a later evaluation; ambiguous genitalia in females). Documentation of one or both parents' genotypes may be required to confirm the subject's genotype

Must not have

Asthma or other condition requiring treatment with systemic corticosteroids within the past 3 months. Asthma treatment with inhaled corticosteroids is permitted

Treatment with potentially hepatotoxic medications (statins); strong inhibitors of CYP3A4 (ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), or CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). CYP2C8 substrates (rosiglitazone, pioglitazone, rapaglinide) and CYP2D6 substrates (dextromethorphan, thioridazine) should be avoided

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 7 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new pill called abiraterone acetate for young children with a hormone problem called congenital adrenal hyperplasia. These children usually need high doses of their regular medicine, which can slow their growth. The new pill aims to reduce the amount of problematic hormones, so they might need less of their usual medicine.

Who is the study for?

This trial is for pre-pubescent children with classic 21-hydroxylase deficiency, which causes congenital adrenal hyperplasia. Eligible participants are girls aged 2-8 and boys aged 2-9 who have not yet reached advanced stages of puberty and require specific hormone treatments. Children with significant heart, liver, kidney issues, or other serious health conditions are excluded.

What is being tested?

The study tests the effectiveness of abiraterone acetate in reducing the need for high doses of hydrocortisone in children with CAH. It aims to find the smallest dose that normalizes hormone levels over a week while maintaining standard therapy with hydrocortisone and fludrocortisone.

What are the potential side effects?

Potential side effects include liver problems since abiraterone can affect liver enzymes; it may also cause hormonal imbalances or reactions related to its active ingredients. The exact side effects will be monitored closely due to the young age of participants.

Eligibility Criteria

Inclusion Criteria

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

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I have been taking fludrocortisone and at least 10 mg/m2/day of hydrocortisone for over a month.

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I have a confirmed diagnosis of classic 21-hydroxylase deficiency.

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My child is between 2-8 years old for girls, or 2-9 for boys, and meets the weight and skeletal age requirements.

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Both my parents (or guardians) have signed the consent form, and I have given my assent if I'm 10 or older.

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My androstenedione levels are high even after taking hydrocortisone.

Exclusion Criteria

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

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I haven't taken systemic steroids for asthma or other conditions in the last 3 months.

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I am not taking medications that could harm my liver or affect how other drugs work.

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I have or had hepatitis.

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My liver functions are normal, and I don't have ascites or encephalopathy.

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My kidney tests show higher than normal levels.

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I am not taking growth hormone now and won't during the study.

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I am not allergic to abiraterone acetate or its ingredients.

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I have or had cataracts.

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I have a condition that affects how my body absorbs nutrients.

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I currently have active cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 7 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~7 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 7 days for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Normalization of serum androstenedione level

Other study objectives

Area under the plasma concentration versus time curve (AUC) of abiraterone

Number of adverse events

Peak Plasma Concentration (Cmax)

Side effects data

From 2021 Phase 3 trial • 32 Patients • NCT01517802

10%

Pulmonary Embolism

Diarrhoea

Fall

Skin Laceration

Myocardial Infarction

Cardiac Failure Congestive

Urinary Retention

Nausea

Oesophagitis

Musculoskeletal Pain

Acute Kidney Injury

Vomiting

Aortic Thrombosis

Hypertension

Dyspnoea

Fatigue

Weight Decreased

Lower Respiratory Tract Infection

Urinary Tract Infection

Dehydration

Cerebrovascular Accident

Encephalopathy

Spinal Cord Compression

Syncope

Cardiac Failure

Upper Limb Fracture

Aortic Valve Replacement

100%

80%

60%

40%

20%

Study treatment Arm

Abiraterone Acetate + Prednisone/Prednisolone

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Abiraterone acetate 4 mg/kg/dExperimental Treatment1 Intervention

If the 2 mg/kg/d dosing does not result in androstenedione level normalization, abiraterone acetate will be administered orally at a daily dose of 4 mg/kg for 7 days in addition to the standard of care treatment of hydrocortisone and fludrocortisone.

Group II: Abiraterone acetate 2 mg/kg/dExperimental Treatment1 Intervention

If the 1 mg/kg/d dosing does not result in androstenedione level normalization, abiraterone acetate will be administered orally at a daily dose of 2 mg/kg for 7 days in addition to the standard of care treatment of hydrocortisone and fludrocortisone.

Group III: Abiraterone acetate 1 mg/kg/dExperimental Treatment1 Intervention

Abiraterone acetate will be administered orally at a daily dose of 1 mg/kg for 7 days in addition to the standard of care treatment of hydrocortisone and fludrocortisone.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Abiraterone acetate

2014

Completed Phase 3

~3440

0 / 15Eligibility 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

Common treatments for Congenital Adrenal Hyperplasia (CAH) include hydrocortisone and abiraterone acetate. Hydrocortisone replaces deficient cortisol and suppresses excess adrenal androgen production, which is crucial for preventing accelerated skeletal maturation and other androgen-related complications. Abiraterone acetate inhibits the CYP17 enzyme, directly reducing androgen production. This dual approach helps manage androgen levels more effectively while minimizing the need for high doses of hydrocortisone, thereby reducing the risk of growth retardation and other side effects associated with long-term glucocorticoid use.