CAH - Congenital Adrenal Hyperplasia
Conditions
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).
Interventions
DRUGCrinecerfont
Crinecerfont administered orally for 14 consecutive days.
Sponsors
Neurocrine Biosciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (Morning Window Average) | Baseline, Day 14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (24-hour Period) | Baseline, Day 14 | 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. |
| Percent Change From Baseline to Day 14 in Adrenocorticotropic Hormone (ACTH) (Morning Window Averages) | Baseline, Day 14 | 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. |
| Percent Change From Baseline to Day 14 in Androstenedione (Morning Window Averages) | Baseline, Day 14 | 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. |
| Percent Change From Baseline to Day 14 in Testosterone (Morning Window Averages) | Baseline, Day 14 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Crinecerfont 50 BID Participants received crinecerfont 50 mg BID orally for 14 consecutive days. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Crinecerfont 50 BID |
|---|---|
| 17-hydroxyprogesterone (OHP) (Morning Window Average) | 7703.74 nanograms/deciliter (ng/dL) |
| 17-OHP (24-Hour Average) | 2739.74 ng/dL |
| Adrenocorticotropic hormone (ACTH) (Morning Window Average) | 226.23 picograms/milliliter (pg/mL) |
| Age, Continuous | 15.0 years STANDARD_DEVIATION 0.9 |
| Androstenedione Morning Window Average) | 367.88 ng/dL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized White | 7 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
| Testosterone (Morning Window Average) Female | 63.50 ng/dL |
| Testosterone (Morning Window Average) Male | 222.00 ng/dL |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 6 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
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.
Time frame: Baseline, Day 14
Population: Pharmacodynamic (PD) analysis set included all enrolled participants who received at least one dose of study drug and had at least one PD parameter measurement at baseline and at least one PD parameter measurement at the Day 14 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crinecerfont 50 mg | Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (Morning Window Average) | -69.48 percent change |
Secondary
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.
Time frame: Baseline, Day 14
Population: PD analysis set included all enrolled participants who received at least one dose of study drug and had at least one PD parameter measurement at baseline and at least one PD parameter measurement at the Day 14 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crinecerfont 50 mg | Percent Change From Baseline to Day 14 in Adrenocorticotropic Hormone (ACTH) (Morning Window Averages) | -57.12 percent change |
Secondary
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.
Time frame: Baseline, Day 14
Population: PD analysis set included all enrolled participants who received at least one dose of study drug and had at least one PD parameter measurement at baseline and at least one PD parameter measurement at the Day 14 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crinecerfont 50 mg | Percent Change From Baseline to Day 14 in Androstenedione (Morning Window Averages) | -58.27 percent change |
Secondary
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.
Time frame: Baseline, Day 14
Population: PD analysis set included all enrolled participants who received at least one dose of study drug and had at least one PD parameter measurement at baseline and at least one PD parameter measurement at the Day 14 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crinecerfont 50 mg | Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (24-hour Period) | -76.0 percent change |
Secondary
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.
Time frame: Baseline, Day 14
Population: PD analysis set included all enrolled participants who received at least one dose of study drug and had at least one PD parameter measurement at baseline and at least one PD parameter measurement at the Day 14 visit. The overall number of participants analyzed is based on male and female participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Crinecerfont 50 mg | Percent Change From Baseline to Day 14 in Testosterone (Morning Window Averages) | Female | -76.18 percent change |
| Crinecerfont 50 mg | Percent Change From Baseline to Day 14 in Testosterone (Morning Window Averages) | Male | 1.39 percent change |