Clinical trial NCT04045145: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 (Crinecerfont) in Pediatric Participants With Congenital Adrenal Hyperplasia
Official title: A Phase 2, Open-Label, Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Pediatric Subjects With Congenital Adrenal Hyperplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: CAH - Congenital Adrenal Hyperplasia
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
First posted: 2019-08-05
Enrollment: 8
Sex: ALL
Minimum age (years): 14
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, open-label, multiple-dose, study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NBI-74788 (crinecerfont) in pediatric participants (14 to 17 years of age) with a documented medical diagnosis of classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH).


Eligibility criteria: Inclusion Criteria:

1. Be in good general health.
2. Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency CAH.
3. Be on a stable regimen of steroidal treatment for CAH that is expected to remain stable throughout the study.
4. Participants of childbearing potential must be instructed on the proper use of barrier methods of contraception and agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently from screening until the final study visit or a prespecified window after the last dose of study drug, whichever is longer.
5. Participants of childbearing potential must have a negative pregnancy test at screening and negative urine pregnancy test at baseline.
6. Have a negative urine drug (for illegal drugs) and alcohol breath test at screening and baseline.
7. Be willing and able to adhere to the study regimen and study procedures described in the protocol and informed consent/assent form, including all requirements at the study center and return for the follow-up visit.

Exclusion Criteria:

1. Have a clinically significant unstable medical condition or chronic disease, or malignancy.
2. Had a medically significant illness within 30 days of screening.
3. Have a known or suspected differential diagnosis of any of the other known forms of classic CAH.
4. Have a history that includes bilateral adrenalectomy, hypopituitarism, or other condition requiring daily therapy with orally administered glucocorticoids.
5. Are pregnant or lactating females.
6. Have a history of epilepsy or serious head injury.
7. Have a known history of long QT syndrome or cardiac tachy-arrhythmia.
8. Have hypersensitivity to any corticotropin releasing hormone antagonists.
9. Test positive at screening for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), or have a history of a positive result.
10. Have a recent history of alcohol or drug abuse, or current evidence of substance dependence or abuse criteria.
11. Used any anticoagulants or antiplatelet therapies within 30 days before screening.
12. Have an active bleeding disorder.
13. Used any other investigational drug within 30 days before initial screening, or plans to use an investigational drug (other than the study drug) during the study.
14. Have a blood loss ≥250 mL or donated blood within 56 days or donated plasma within 7 days before baseline.

Primary outcomes:
measure: Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (Morning Window Average)
timeFrame: Baseline, Day 14
Secondary outcomes:
measure: Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (24-hour Period)
timeFrame: Baseline, Day 14
measure: Percent Change From Baseline to Day 14 in Adrenocorticotropic Hormone (ACTH) (Morning Window Averages)
timeFrame: Baseline, Day 14
measure: Percent Change From Baseline to Day 14 in Androstenedione (Morning Window Averages)
timeFrame: Baseline, Day 14
measure: Percent Change From Baseline to Day 14 in Testosterone (Morning Window Averages)
timeFrame: Baseline, Day 14
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Neurocrine Clinical Site
state: California
city: Aurora
country: United States
facility: Neurocrine Clinical Site
state: Colorado
city: Ann Arbor
country: United States
facility: Neurocrine Clinical Site
state: Michigan
city: Minneapolis
country: United States
facility: Neurocrine Clinical Site
state: Minnesota
city: Philadelphia
country: United States
facility: Neurocrine Clinical Site
state: Pennsylvania
city: Seattle
country: United States
facility: Neurocrine Clinical Site
state: Washington
Study officials:
References:
citation: Newfield RS, Sarafoglou K, Fechner PY, Nokoff NJ, Auchus RJ, Vogiatzi MG, Jeha GS, Giri N, Roberts E, Sturgeon J, Chan JL, Farber RH. Crinecerfont, a CRF1 Receptor Antagonist, Lowers Adrenal Androgens in Adolescents With Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2023 Oct 18;108(11):2871-2878. doi: 10.1210/clinem/dgad270.