Androgen Reduction in Congenital Adrenal Hyperplasia, Phase 1

• Register: ClinicalTrials.gov
• Last refreshed on: 25 March 2024
• Main ID: NCT02574910
• Date of registration: 24/04/2015
• Prospective Registration: Yes
• Primary sponsor: University of Texas Southwestern Medical Center
• Public title: Androgen Reduction in Congenital Adrenal Hyperplasia, Phase 1
• Scientific title: A Phase 1 Multi-Center Study to Assess the Efficacy and Safety of Abiraterone Acetate as Adjunctive Therapy in Pre-Pubescent Children With Classic 21-Hydroxylase Deficiency
• Date of first enrolment: August 1, 2017
• Target sample size: 36
• Recruitment status: Suspended
• URL: https://clinicaltrials.gov/ct2/show/NCT02574910
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Perrin C White, MD
• Affiliation: UT Southwestern Medical Center

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Pre-pubescent girls (age 2 years [12 kg minimum] to 8 years inclusive; skeletal age
<10 years) or boys (age 2 years [12 kg] to 9 years inclusive; skeletal age <11 years).

2. 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.

3. 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.

4. Morning serum androstenedione concentrations >1.5 x Upper limit normal (ULN) after 7
days of dosing with doses of hydrocortisone required for physiologic replacement.

5. At least one parent (or other legally acceptable representative) must sign the
informed consent form before the performance of any study procedures, but both parents
must sign if both have parental rights. Children who are capable of providing assent
(typically 10 years of age and older) must sign an assent form before the performance
of any study procedures

Exclusion Criteria:

1. Evidence of central puberty: Tanner Stage >2 for breast development in girls or
testicular volume >4 mL in boys, or random luteinizing hormone (LH) >0.3
milli-international units (mIU)/mL. Subjects with pubic and/or axillary hair as the
only sign of puberty onset will be allowed.

2. Current or history of hepatitis from any etiology, including history of active viral
hepatitis A, B, or C.

3. Patients with baseline hepatic impairment are excluded from this trial. To be eligible
for this protocol, patients must meet all of the following criteria:

AST, ALT and Total bilirubin < ULN Albumin > lower limits of normal (LLN) No evidence
of ascites No evidence of encephalopathy

4. Abnormalities of liver function developing during the study

5. Abnormal renal function tests, defined as blood urea nitrogen (BUN) or creatinine >1.5
ULN for age.

6. Significant anemia (hemoglobin < 12 g/dl). If documented to be due to iron deficiency,
subjects may be rescreened 3 months after this has been treated.

7. Clinically significant abnormality in the 12-lead electrocardiogram (ECG)

8. A history of a malabsorption syndrome.

9. Evidence of active malignancy.

10. Serious or uncontrolled co-existent disease, including active or uncontrolled
infection. Subjects may be rescreened after resolution of any such condition.

11. Concurrent medical condition or disease other than 21-hydroxylase deficiency that may
interfere with linear growth or that requires concomitant therapy that is likely to
interfere with study procedures or results.

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

13. 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

14. Treatment with medications to affect puberty or synthesis of sex steroids, including
gonadotropin releasing hormone agonists, aromatase inhibitors, or androgen receptor
blockers (e.g., flutamide, spironolactone). However, a gonadotropin releasing hormone
agonist may be started during the study for treatment-emergent central puberty without
disqualifying the subject

15. Treatment with growth hormone at enrollment or during the course of the study.

16. Known allergies, hypersensitivity, or intolerance to abiraterone acetate or its
excipients (refer to United States Prescribing Information).

17. Has received an investigational drug within 4 weeks of the planned first dose of study
drug or is currently enrolled in an investigational interventional study.

18. Any condition that, in the opinion of the investigator, would make participation not
be in the best interest (eg, compromise the well-being) of the subject or that could
prevent, limit, or confound the protocol-specified assessments.

19. Presence or history of cataracts.



Age minimum: 2 Years
Age maximum: 9 Years
Gender: All

Health Condition(s) or Problem(s) studied

Congenital Adrenal Hyperplasia

Intervention(s)

Drug: Abiraterone acetate

Primary Outcome(s)

Normalization of serum androstenedione level [Time Frame: 7 days]

Secondary Outcome(s)

Dihydrotestosterone levels [Time Frame: 7 days]

17-hydroxyprogesterone levels [Time Frame: 7 days]

Secondary ID(s)

1U01HD083493-01

112014-087

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Children's Hospital Los Angeles

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

University of Michigan