A Phase 1-2 Multi-Center Study to Assess the Efficacy and Safety of Abiraterone Acetate as Adjunctive Therapy in Pre-Pubescent Children with Classic 21-Hydroxylase Deficiency
Study ID: STU 112014-087
Children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency tend to have elevated circulating levels of androgens, which can accelerate skeletal maturation and adversely impact adult height. Additionally, these children require supraphysiologic doses of hydrocortisone to suppress secretion of adrenal androgen precursors, and this treatment can retard linear growth. This study seeks to use oral abiraterone acetate (Zytiga)as an adjunct to approved CAH therapy (oral hydrocortisone and fludrocortisone) for pre-pubescent children with classic 21-hydroxylase deficiency in order to reduce daily requirement of hydrocortisone.
Pre-pubescent girls (age 2 years [12 kg] to 8 years inclusive; skeletal age ≤9 years) or boys (age 2 years [12 kg] to 9 years inclusive; skeletal age ≤10 years).
Confirmed classic 21-hydroxylase deficiency evident by genotype groups A, A1 or B, or by clinical course.
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.
Morning serum androstenedione concentrations >1.5 x ULN after 7 days of dosing with doses of hydrocortisone required for physiologic replacement.
Informed consent .
Evidence of central puberty: Tanner Stage >2 for breast development in girls or testicular volume >4 mL in boys, or random LH >0.3 mIU/mL.
Current or history of hepatitis from any etiology.
Abnormal liver function tests (transaminases>3X ULN).
Abnormal renal function tests (BUN or creatinine >1.5 ULN).
Significant anemia (hemoglobin < 12 g/dl).
Clinically significant ECG abnormality
A history of a malabsorption syndrome.
Evidence of active malignancy.
Co-existent disease that may interfere with linear growth or that requires concomitant therapy that is likely to interfere with study procedures or results.
Treatment with potentially hepatotoxic medications, CYP2D6, strong inhibitors or inducers of CYP3A4
Treatment with medications to affect puberty or synthesis of sex steroids, including gonadotropin releasing hormone agonists, aromatase inhibitors, or androgen receptor blockers
Treatment with growth hormone
Known allergies, hypersensitivity, or intolerance to abiraterone acetate or its excipients.