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

NCT04045145 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NBI-74788-CAH2008
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 6

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).

Conditions

CAH - Congenital Adrenal Hyperplasia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (24-hour Period)

  Baseline, Day 14

• Percent Change From Baseline to Day 14 in Adrenocorticotropic Hormone (ACTH) (Morning Window Averages)

  Baseline, Day 14

• Percent Change From Baseline to Day 14 in Androstenedione (Morning Window Averages)

  Baseline, Day 14

• Percent Change From Baseline to Day 14 in Testosterone (Morning Window Averages)

  Baseline, Day 14

Study Arms (1)

Crinecerfont 50 milligrams (mg) Twice Daily (BID)

EXPERIMENTAL

Crinecerfont administered orally for 14 consecutive days.

Drug: Crinecerfont

Interventions

Crinecerfont DRUG

Crinecerfont administered orally for 14 consecutive days.

Also known as: NBI-74788

Crinecerfont 50 milligrams (mg) Twice Daily (BID)

Eligibility Criteria

• Age: 14 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Be in good general health.
• Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency CAH.
• Be on a stable regimen of steroidal treatment for CAH that is expected to remain stable throughout the study.
• 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.
• Participants of childbearing potential must have a negative pregnancy test at screening and negative urine pregnancy test at baseline.
• Have a negative urine drug (for illegal drugs) and alcohol breath test at screening and baseline.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Neurocrine Biosciences: lead

Study Sites (6)

Neurocrine Clinical Site

San Diego, California, 92123, United States

Location

Neurocrine Clinical Site

Aurora, Colorado, 80045, United States

Location

Neurocrine Clinical Site

Ann Arbor, Michigan, 48109, United States

Location

Neurocrine Clinical Site

Minneapolis, Minnesota, 55454, United States

Location

Neurocrine Clinical Site

Philadelphia, Pennsylvania, 19104, United States

Location

Neurocrine Clinical Site

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• 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.

  PMID: 37216921 RESULT

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital

Interventions

crinecerfont

Condition Hierarchy (Ancestors)

Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Neurocrine Medical Information Call Center
• Organization: Neurocrine Biosciences

medinfo@neurocrine.com

877-641-3461

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 5, 2019
• Study Start: December 12, 2019
• Primary Completion: July 2, 2021
• Study Completion: July 2, 2021
• Last Updated: July 18, 2024
• Results First Posted: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)