Congenital Adrenal Hyperplasia
Conditions
Keywords
classic congenital adrenal hyperplasia (CAH), 21-hydroxylase deficiency
Brief summary
This is a Phase 3 study to evaluate the efficacy, safety, and tolerability of crinecerfont versus placebo administered for 28 weeks in approximately 81 pediatric participants with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The study consists of a 28-week double blind, placebo-controlled period, followed by 24 weeks of open-label treatment with crinecerfont. Subsequently, participants may elect to participate in the open-label extension (OLE) period. The duration of participation in the study is approximately 14 months for the core study and will be a variable amount of time per participant for the OLE (estimated to be approximately 3 years).
Interventions
DRUGCrinecerfont
CRF type 1 receptor antagonist
DRUGPlacebo
Non-active dosage form
Sponsors
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Be willing and able to adhere to the study procedures, including all requirements at the study center, and return for the follow-up visit. * Have a medically confirmed diagnosis of classic CAH due to 21-hydroxylase deficiency. * Be on a stable steroid regimen. * Have elevated androgen levels. * Participants of childbearing potential must be abstinent or agree to use appropriate birth control during the study.
Exclusion criteria
* Have a diagnosis of any of the other forms of classic CAH. * Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy. * Have a clinically significant unstable medical condition or chronic disease other than CAH. * Have a history of cancer unless considered to be cured. * Have a known history of clinically significant arrhythmia or abnormalities on electrocardiogram (ECG). * Have a known hypersensitivity to any corticotropin-releasing hormone antagonist. * Have received an investigational drug within 30 days before initial screening or plan to use an investigational drug (other than the study drug) during the study. * Have current substance dependence or substance (drug) or alcohol abuse. * Have had a significant blood loss or donated blood or blood products within 8 weeks prior to the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum Androstenedione at Week 4 | Baseline, Week 4 | Blood serum samples were collected for the analysis of serum androstenedione concentrations. Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model. |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Glucocorticoid Daily Dose at Week 28 | Baseline, Week 28 |
| Number of Participants Who Achieved a Reduction to Physiologic Glucocorticoid Dose While Maintaining Androstenedione Control at Week 28 | Week 28 |
| Change From Baseline in Serum 17-hydroxyprogesterone (17-OHP) at Week 4 | Baseline, Week 4 |
| Change From Baseline in Mean 24-hour Salivary 17-OHP at Week 28 | Baseline, Week 28 |
| Change From Baseline in the Ratio of Bone Age to Chronological Age (BA:CA) at Week 28 | Baseline, Week 28 |
| Change From Baseline in Body Mass Index (BMI) Standard Deviation Score (SDS) at Week 28 | Baseline, Week 28 |
Countries
Belgium, Canada, France, Germany, Greece, Italy, Poland, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
The study includes a double-blind (DB) placebo-controlled treatment period, an open-label (OL) treatment period, and an open-label extension (OLE) period. The OL treatment period and OLE period of the study is ongoing. Only the primary analysis results (as of 09 August 2023 data cutoff date) have been reported. The final results will be reported after completion of the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received crinecerfont-matched placebo orally twice daily for 28 weeks during the DB placebo-controlled treatment period. After the 28-week DB placebo-controlled treatment period, there was a 24-week, OL treatment period, during which all participants received crinecerfont at doses based on their Week 28 body weight. | 34 |
| Crinecerfont Participants received crinecerfont orally twice daily for 28 weeks during the DB placebo-controlled treatment period. Dose assignment from Day 1 to Week 28 was based on the participant's weight at Day 1. After the 28-week DB placebo-controlled treatment period, there was a 24-week, OL treatment period, during which all participants received crinecerfont at doses based on their Week 28 body weight. | 69 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| DB Treatment Period (28 Weeks) | Adverse Event | 0 | 2 |
| DB Treatment Period (28 Weeks) | Withdrawal by Subject | 3 | 1 |
| OL Treatment Period (24 Weeks) | Ongoing in the Study | 16 | 37 |
Baseline characteristics
| Characteristic | Crinecerfont | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 12.022 years STANDARD_DEVIATION 3.405 | 12.061 years STANDARD_DEVIATION 3.484 | 12.142 years STANDARD_DEVIATION 3.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 11 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 77 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 15 Participants | 6 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 7 Participants | 9 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Multiple | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not Collected | 9 Participants | 15 Participants | 6 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 42 Participants | 65 Participants | 23 Participants |
| Serum Androstenedione Concentration | 404.96 nanograms (ng)/deciliter (dL) STANDARD_DEVIATION 464.1 | 430.83 nanograms (ng)/deciliter (dL) STANDARD_DEVIATION 460.58 | 483.32 nanograms (ng)/deciliter (dL) STANDARD_DEVIATION 455.64 |
| Sex: Female, Male Female | 34 Participants | 50 Participants | 16 Participants |
| Sex: Female, Male Male | 35 Participants | 53 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 69 |
| other Total, other adverse events | 22 / 33 | 51 / 69 |
| serious Total, serious adverse events | 4 / 33 | 1 / 69 |
Outcome results
Primary
Change From Baseline in Serum Androstenedione at Week 4
Blood serum samples were collected for the analysis of serum androstenedione concentrations. Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model.
Time frame: Baseline, Week 4
Population: Full Analysis Set included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Serum Androstenedione at Week 4 | 70.986 ng/dL | Standard Error 56.198 |
| Crinecerfont | Change From Baseline in Serum Androstenedione at Week 4 | -196.789 ng/dL | Standard Error 39.369 |
p-value: 0.000295% CI: [-403.427, -132.124]ANCOVA
Secondary
Change From Baseline in Body Mass Index (BMI) Standard Deviation Score (SDS) at Week 28
Time frame: Baseline, Week 28
Secondary
Change From Baseline in Mean 24-hour Salivary 17-OHP at Week 28
Time frame: Baseline, Week 28
Secondary
Change From Baseline in Serum 17-hydroxyprogesterone (17-OHP) at Week 4
Time frame: Baseline, Week 4
Secondary
Change From Baseline in the Ratio of Bone Age to Chronological Age (BA:CA) at Week 28
Time frame: Baseline, Week 28
Secondary
Number of Participants Who Achieved a Reduction to Physiologic Glucocorticoid Dose While Maintaining Androstenedione Control at Week 28
Time frame: Week 28
Secondary
Percent Change From Baseline in Glucocorticoid Daily Dose at Week 28
Time frame: Baseline, Week 28