Trial Outcomes & Findings for Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia (NCT NCT04490915)

NCT ID: NCT04490915

Last Updated: 2025-02-05

Results Overview

Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

182 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2025-02-05

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.
DB Treatment Period (24 Weeks) STARTED	60	122
DB Treatment Period (24 Weeks) Received at Least 1 Dose of Study Drug	59	122
DB Treatment Period (24 Weeks) COMPLETED	57	117
DB Treatment Period (24 Weeks) NOT COMPLETED	3	5
OL Treatment Period (6 Months) STARTED	57	117
OL Treatment Period (6 Months) Received at Least 1 Dose of Study Drug	57	117
OL Treatment Period (6 Months) COMPLETED	22	57
OL Treatment Period (6 Months) NOT COMPLETED	35	60

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
DB Treatment Period (24 Weeks) Withdrawal by Subject	2	3
DB Treatment Period (24 Weeks) Lost to Follow-up	1	1
DB Treatment Period (24 Weeks) Adverse Event	0	1
OL Treatment Period (6 Months) Withdrawal by Subject	1	0
OL Treatment Period (6 Months) Lost to Follow-up	0	1
OL Treatment Period (6 Months) Adverse Event	0	1
OL Treatment Period (6 Months) Ongoing in the Study	34	58

Baseline Characteristics

Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=60 Participants 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.	Crinecerfont n=122 Participants 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.	Total n=182 Participants Total of all reporting groups
Age, Continuous	29.8 years STANDARD_DEVIATION 10.17 • n=5 Participants	31.3 years STANDARD_DEVIATION 9.82 • n=7 Participants	30.8 years STANDARD_DEVIATION 9.93 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	61 Participants n=7 Participants	90 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	61 Participants n=7 Participants	92 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	52 Participants n=5 Participants	116 Participants n=7 Participants	168 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	57 Participants n=5 Participants	107 Participants n=7 Participants	164 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Daily Glucocorticoid Dose	32.06 milligrams (mg)/day STANDARD_DEVIATION 32.06 • n=5 Participants	32.44 milligrams (mg)/day STANDARD_DEVIATION 9.24 • n=7 Participants	32.31 milligrams (mg)/day STANDARD_DEVIATION 9.30 • n=5 Participants
Daily Glucocorticoid Dose Adjusted for Body Surface Area	17.91 mg/square meter (m^2)/day STANDARD_DEVIATION 5.45 • n=5 Participants	17.45 mg/square meter (m^2)/day STANDARD_DEVIATION 4.54 • n=7 Participants	17.60 mg/square meter (m^2)/day STANDARD_DEVIATION 4.85 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set included all randomized participants.

Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received crinecerfont-matched placebo orally twice daily for 24 weeks during the DB placebo-controlled treatment period.	Crinecerfont n=122 Participants Participants received crinecerfont orally twice daily for 24 weeks during the DB placebo-controlled treatment period.
Percent Change From Baseline in Glucocorticoid Daily Dose at Week 24	-10.300 percent change Standard Error 3.247	-27.322 percent change Standard Error 2.418

Adverse Events

DB Period: Placebo

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

DB Period: Crinecerfont

Serious events: 4 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DB Period: Placebo n=59 participants at risk Participants received crinecerfont-matched placebo orally twice daily for 24 weeks during the DB placebo-controlled treatment period.	DB Period: Crinecerfont n=122 participants at risk Participants received crinecerfont orally twice daily for 24 weeks during the DB placebo-controlled treatment period.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	0.82% 1/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Infections and infestations Groin abscess	0.00% 0/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	0.82% 1/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Infections and infestations Cellulitis	0.00% 0/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	0.82% 1/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Endocrine disorders Adrenocortical insufficiency acute	0.00% 0/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	0.82% 1/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Nervous system disorders Presyncope	0.00% 0/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	0.82% 1/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.

Other adverse events

Additional Information

Neurocrine Medical Information Call Center

Neurocrine Biosciences

Phone: 877-641-3461

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	DB Period: Placebo n=59 participants at risk Participants received crinecerfont-matched placebo orally twice daily for 24 weeks during the DB placebo-controlled treatment period.	DB Period: Crinecerfont n=122 participants at risk Participants received crinecerfont orally twice daily for 24 weeks during the DB placebo-controlled treatment period.
General disorders Fatigue	15.3% 9/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	24.6% 30/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Nervous system disorders Headache	15.3% 9/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	15.6% 19/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Infections and infestations Coronavirus infection	8.5% 5/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	13.9% 17/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Infections and infestations Upper respiratory tract infection	11.9% 7/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	9.0% 11/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Gastrointestinal disorders Diarrhoea	8.5% 5/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	8.2% 10/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Nervous system disorders Dizziness	3.4% 2/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	8.2% 10/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Gastrointestinal disorders Nausea	8.5% 5/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	8.2% 10/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	7.4% 9/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Musculoskeletal and connective tissue disorders Back pain	3.4% 2/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	5.7% 7/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
General disorders Pyrexia	10.2% 6/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	5.7% 7/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Infections and infestations Nasopharyngitis	13.6% 8/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	4.9% 6/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Gastrointestinal disorders Vomiting	8.5% 5/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	4.9% 6/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Psychiatric disorders Anxiety	8.5% 5/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	3.3% 4/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Skin and subcutaneous tissue disorders Acne	6.8% 4/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	3.3% 4/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Infections and infestations Urinary tract infection	5.1% 3/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	3.3% 4/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.1% 3/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	2.5% 3/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
General disorders Asthenia	8.5% 5/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	1.6% 2/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Investigations Blood androstenedione increased	5.1% 3/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	1.6% 2/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.
Investigations Renin increased	5.1% 3/59 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.	0.82% 1/122 • Baseline up to Week 24 Per planned analysis all-cause mortality data were collected and reported for all randomized participants. Adverse events (serious and other) were collected and reported for all randomized participants who received at least 1 dose of study drug. Only DB period was complete at the time of data cutoff date.