Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 (Crinecerfont) in Pediatric Participants With Congenital Adrenal Hyperplasia

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

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).

Study Overview

• Status: Completed
• Conditions: CAH - Congenital Adrenal Hyperplasia
• Intervention / Treatment: Drug: Crinecerfont

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Neurocrine Clinical Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Neurocrine Clinical Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Neurocrine Clinical Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • Neurocrine Clinical Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Neurocrine Clinical Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Neurocrine Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crinecerfont 50 milligrams (mg) Twice Daily (BID); Crinecerfont administered orally for 14 consecutive days.	Drug: Crinecerfont; Crinecerfont administered orally for 14 consecutive days.; Other Names: NBI-74788

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (Morning Window Average)	Percent changes in 17-OHP were assessed through the collection of samples from 0700 hours to 1000 hours (morning window) both prior to study drug administration (i.e., baseline) and after 14 days of study drug dosing. The 2 samples collected during this morning window at each visit were averaged and used to determine the percent change from baseline.	Baseline, Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (24-hour Period)	Percent changes in 17-OHP were assessed through the collection of samples for a 24-hour period prior to study drug administration (i.e., baseline) and after 14 days of study drug dosing. The average of each participant's serial sampling values at each visit where serial sampling was performed was calculated and used to determine the percent change from baseline.	Baseline, Day 14
Percent Change From Baseline to Day 14 in Adrenocorticotropic Hormone (ACTH) (Morning Window Averages)	Percent changes in ACTH were assessed through the collection of samples from 0700 hours to 1000 hours (morning window) both prior to study drug administration (i.e., baseline) and after 14 days of study drug dosing. The samples collected during this morning window at each visit were averaged and used to determine the percent change from baseline.	Baseline, Day 14
Percent Change From Baseline to Day 14 in Androstenedione (Morning Window Averages)	Percent changes in androstenedione were assessed through the collection of samples from 0700 hours to 1000 hours (morning window) both prior to study drug administration (i.e., baseline) and after 14 days of study drug dosing. The samples collected during this morning window at each visit were averaged and used to determine the percent change from baseline.	Baseline, Day 14
Percent Change From Baseline to Day 14 in Testosterone (Morning Window Averages)	Percent change in testosterone were assessed through the collection of samples from 0700 hours to 1000 hours (morning window) both prior to study drug administration (i.e., baseline) and after 14 days of study drug dosing. The samples collected during this morning window at each visit were averaged and used to determine the percent change from baseline.	Baseline, Day 14

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences

Publications and helpful links

General Publications

• 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.

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2019
• Primary Completion (Actual): July 2, 2021
• Study Completion (Actual): July 2, 2021

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: August 1, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction
• Other Study ID Numbers: NBI-74788-CAH2008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No