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

Inclusion Criteria:

• 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 .

Exclusion Criteria:

• 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.