Congenital Adrenal Hyperplasia
Conditions
Brief summary
This is a Phase 3 study to evaluate the efficacy, safety, and tolerability of crinecerfont versus placebo administered for 24 weeks in approximately 165 adult participants with classic CAH due to 21-hydroxylase deficiency. The study consists of a 24-week randomized, double-blind, placebo-controlled period, followed by 1 year of active 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 20 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
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be willing and able to adhere to the study procedures, including all requirements at the study center and return for the follow-up visit. 2. Have a medically confirmed diagnosis of classic CAH due to 21-hydroxylase deficiency. 3. Be on a stable steroid regimen. 4. Participants of childbearing potential must agree to use an acceptable method of contraception during the study.
Exclusion criteria
1. Have a diagnosis of any of the other known forms of classic CAH. 2. Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy. 3. Have a clinically significant unstable medical condition or chronic disease other than CAH. 4. Have a history of cancer unless considered cured. 5. Are pregnant. 6. Have a known history of clinically significant arrhythmia or abnormalities on ECG. 7. Have a known hypersensitivity to any corticotropin releasing hormone receptor antagonists. 8. Have received any other investigational drug within 30 days before initial screening or plan to use an investigational drug (other than the study drug) during the study. 9. Have current substance dependence, or current substance (drug) or alcohol abuse. 10. Have had a blood loss ≥550 mL or donated blood or blood products within 8 weeks prior to the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Glucocorticoid Daily Dose at Week 24 | Baseline, Week 24 | Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model. |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Serum Androstenedione at Week 4 | Baseline, Week 4 |
| Number of Participants Who Achieved a Reduction to Physiologic Glucocorticoid Dose While Maintaining Androstenedione Control at Week 24 | Week 24 |
| Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 | Baseline, Week 24 |
| Percent Change From Baseline in Body Weight at Week 24 | Baseline, Week 24 |
| Change From Baseline in Percent Total Fat Mass at Week 24 | Baseline, Week 24 |
| Change From Baseline in Serum 17-hydroxyprogesterone (17-OHP) at Week 4 | Baseline, Week 4 |
| Change From Baseline in Blood Pressure at Week 24 | Baseline, Week 24 |
| Change From Baseline in Glucose Tolerance at Week 24 | Baseline, Week 24 |
| Change From Baseline in Waist Circumference at Week 24 | Baseline, Week 24 |
| Change From Baseline in Menstrual Regularity at Week 24 | Baseline, Week 24 |
| Change From Baseline in Testicular Adrenal Rest Tumor (TART) Volume at Week 24 | Baseline, Week 24 |
Countries
Austria, Belgium, Bulgaria, Canada, Czechia, France, Germany, Greece, Israel, Italy, Netherlands, Poland, Portugal, Serbia, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Development Lead
Neurocrine Biosciences
Participant flow
Pre-assignment details
The study includes a double-blind (DB) placebo-controlled treatment period, an open-label (OL) treatment period, an OL or DB active-controlled treatment period, and an open-label extension (OLE) treatment period. The study is ongoing. Only the primary analysis results (as of 19 July 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 24 weeks during the DB placebo-controlled treatment period. After the 24-week DB placebo-controlled treatment period, there was a 6-month, OL treatment period, during which all participants received crinecerfont. | 60 |
| Crinecerfont Participants received crinecerfont orally twice daily for 24 weeks during the DB placebo-controlled treatment period. After the 24-week DB placebo-controlled treatment period, there was a 6-month, OL treatment period, during which all participants received crinecerfont. | 122 |
| Total | 182 |
Baseline characteristics
| Characteristic | Crinecerfont | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 31.3 years STANDARD_DEVIATION 9.82 | 29.8 years STANDARD_DEVIATION 10.17 | 30.8 years STANDARD_DEVIATION 9.93 |
| Daily Glucocorticoid Dose | 32.44 milligrams (mg)/day STANDARD_DEVIATION 9.24 | 32.06 milligrams (mg)/day STANDARD_DEVIATION 32.06 | 32.31 milligrams (mg)/day STANDARD_DEVIATION 9.3 |
| Daily Glucocorticoid Dose Adjusted for Body Surface Area | 17.45 mg/square meter (m^2)/day STANDARD_DEVIATION 4.54 | 17.91 mg/square meter (m^2)/day STANDARD_DEVIATION 5.45 | 17.60 mg/square meter (m^2)/day STANDARD_DEVIATION 4.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 8 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 116 Participants | 52 Participants | 168 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) White | 107 Participants | 57 Participants | 164 Participants |
| Sex: Female, Male Female | 61 Participants | 29 Participants | 90 Participants |
| Sex: Female, Male Male | 61 Participants | 31 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 122 |
| other Total, other adverse events | 39 / 59 | 76 / 122 |
| serious Total, serious adverse events | 0 / 59 | 4 / 122 |
Outcome results
Primary
Percent Change From Baseline in Glucocorticoid Daily Dose at Week 24
Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model.
Time frame: Baseline, Week 24
Population: Full Analysis Set included all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Glucocorticoid Daily Dose at Week 24 | -10.300 percent change | Standard Error 3.247 |
| Crinecerfont | Percent Change From Baseline in Glucocorticoid Daily Dose at Week 24 | -27.322 percent change | Standard Error 2.418 |
p-value: <0.000195% CI: [-23.802, -10.243]ANCOVA
Secondary
Change From Baseline in Blood Pressure at Week 24
Time frame: Baseline, Week 24
Secondary
Change From Baseline in Glucose Tolerance at Week 24
Time frame: Baseline, Week 24
Secondary
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24
Time frame: Baseline, Week 24
Secondary
Change From Baseline in Menstrual Regularity at Week 24
Time frame: Baseline, Week 24
Secondary
Change From Baseline in Percent Total Fat Mass at Week 24
Time frame: Baseline, Week 24
Secondary
Change From Baseline in Serum 17-hydroxyprogesterone (17-OHP) at Week 4
Time frame: Baseline, Week 4
Secondary
Change From Baseline in Serum Androstenedione at Week 4
Time frame: Baseline, Week 4
Secondary
Change From Baseline in Testicular Adrenal Rest Tumor (TART) Volume at Week 24
Time frame: Baseline, Week 24
Secondary
Change From Baseline in Waist Circumference at Week 24
Time frame: Baseline, Week 24
Secondary
Number of Participants Who Achieved a Reduction to Physiologic Glucocorticoid Dose While Maintaining Androstenedione Control at Week 24
Time frame: Week 24
Secondary
Percent Change From Baseline in Body Weight at Week 24
Time frame: Baseline, Week 24