NCT03548246

Brief Summary

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jan 2023

Typical duration for phase_2

Geographic Reach
1 country

4 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 24, 2015

Completed
3.1 years until next milestone

First Posted

Study publicly available on registry

June 7, 2018

Completed
4.6 years until next milestone

Study Start

First participant enrolled

January 1, 2023

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2026

Completed
Last Updated

February 1, 2023

Status Verified

January 1, 2023

Enrollment Period

3 years

First QC Date

April 24, 2015

Last Update Submit

January 30, 2023

Conditions

Congenital Adrenal Hyperplasia

Outcome Measures

Primary Outcomes (1)

  • Bone age advancement

    Advancement from baseline in radiographically determined skeletal maturation

    104 weeks

Secondary Outcomes (5)

  • Weight

    104 weeks

  • Body mass index Z-score

    104 weeks

  • Predicted adult height

    104 weeks

  • Hydrocortisone dose required to normalize androstenedione levels

    104 weeks

  • Number of adverse events

    104 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Daily placebo, plus usual maintenance treatment with hydrocortisone and fludrocortisone.

Drug: PlaceboDrug: HydrocortisoneDrug: Fludrocortisone

Abiraterone acetate

EXPERIMENTAL

Abiraterone acetate administered daily in dose determined in Phase 1, plus usual maintenance treatment with hydrocortisone and fludrocortisone..

Drug: Abiraterone acetateDrug: HydrocortisoneDrug: Fludrocortisone

Interventions

Abiraterone acetateDRUG

Daily oral abiraterone acetate for 2 years. The dose will be specified based on pharmacodynamic data from Phase 1.

Also known as: Zytiga
Abiraterone acetate
PlaceboDRUG

Daily placebo for 2 years.

Placebo
HydrocortisoneDRUG

Hydrocortisone will be administered at a starting dose of 7-9 mg/M2/d and adjusted as necessary based on 17-hydroxyprogesterone and ACTH levels.

Abiraterone acetatePlacebo
FludrocortisoneDRUG

Fludrocortisone will be administered at the dose the subject was taking a study entry and adjusted as necessary to keep plasma renin in the high normal range.

Abiraterone acetatePlacebo

Eligibility Criteria

Age2 Years - 9 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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 .

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

National Institutes of Health

Bethesda, Maryland, 20892, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Children's Medical Center

Dallas, Texas, 75235, United States

Location

Related Publications (1)

  • Auchus RJ, Buschur EO, Chang AY, Hammer GD, Ramm C, Madrigal D, Wang G, Gonzalez M, Xu XS, Smit JW, Jiao J, Yu MK. Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2014 Aug;99(8):2763-70. doi: 10.1210/jc.2014-1258. Epub 2014 Apr 29.

    PMID: 24780050BACKGROUND

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital

Interventions

Abiraterone AcetateHydrocortisoneFludrocortisone

Condition Hierarchy (Ancestors)

Adrenogenital SyndromeDisorders of Sex DevelopmentUrogenital AbnormalitiesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, InbornSteroid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsMetabolic DiseasesNutritional and Metabolic DiseasesAdrenal Gland DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

AndrostenesAndrostanesSteroidsFused-Ring CompoundsPolycyclic CompoundsPregnenedionesPregnenesPregnanes11-HydroxycorticosteroidsHydroxycorticosteroidsAdrenal Cortex HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists17-Hydroxycorticosteroids

Study Officials

  • Perrin C White, MD

    University of Texas Southwestern Medical Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

April 24, 2015

First Posted

June 7, 2018

Study Start

January 1, 2023

Primary Completion

January 1, 2026

Study Completion

January 1, 2026

Last Updated

February 1, 2023

Record last verified: 2023-01

Locations

US(4)