The purpose of this Phase 2, open-label, sequential dose cohort study is to evaluate the safety, efficacy, and pharmacokinetics (PK) of atumelnant (CRN04894) in participants with classic congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency.
This Phase 2, open-label, sequential dose cohort study will evaluate the efficacy, safety, PK, and PD of atumelnant (CRN04894) when administered for 12 weeks in participants with CAH caused by 21-hydroxylase deficiency. Up to 42 participants will be enrolled in the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Atumelnant is an orally active nonpeptide melanocortin 2 receptor (MC2R) or adrenocorticotropic hormone (ACTH) antagonist.
Crinetics Study Site
Pasadena, California, United States
Change From Baseline in Morning (Before 11:00) Serum Androstenedione (A4) PM Dosing
A4 is the principal biochemical measure of disease activity in adult CAH. Blood samples were collected for the measurement of serum concentration of A4 prior to glucocorticoid administration. Baseline is defined as the last non-missing morning window value prior to or on the same day as the first dose date of atumelnant. Change from baseline was obtained by subtracting post-baseline visit value minus baseline value.
Time frame: Baseline and Week 12
Change From Baseline in Morning (Before 11:00) Serum Androstenedione (A4) AM Dosing
A4 is the principal biochemical measure of disease activity in adult CAH. Blood samples were collected for the measurement of serum concentration of A4 prior to glucocorticoid administration. Baseline is defined as the last non-missing morning window value prior to or on the same day as the first dose date of atumelnant. Change from baseline was obtained by subtracting post-baseline visit value minus baseline value.
Time frame: Baseline and Week 12
Number of Participants Reporting of Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events Leading to Discontinuation Throughout the Study
An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. TEAEs were collected in the full analysis set which consisted of all participants who received at least one dose of study drug. A serious AE is defined by its severe clinical consequences: it is any event that results in death, is life-threatening, requires inpatient hospitalization, results in persistent disability, or requires medical intervention to prevent these outcomes.
Time frame: From Day 1 to Up to Week 16 (End of study)
Change From Baseline in Morning (Before 11:00) Serum 17-hydroxyprogesterone (17-OHP) PM Dosing
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Crinetics Study Site
Ann Arbor, Michigan, United States
Crinetics Study Site
Minneapolis, Minnesota, United States
Crinetics Study Site
St Louis, Missouri, United States
Crinetics Study Site
Morehead City, North Carolina, United States
Crinetics Study Site
Cleveland, Ohio, United States
Crinetics Study Site
Philadelphia, Pennsylvania, United States
Crinetics Study Site
East Providence, Rhode Island, United States
Crinetics Study Site
Córdoba, Córdoba Province, Argentina
Crinetics Study Site
Buenos Aires, Argentina
...and 17 more locations
Elevated levels of the immediate enzyme substrate 17-OHP are indicative of CAH. The secondary efficacy endpoint was change from baseline in morning serum 17-OHP at Week 12. Baseline is defined as the last non-missing morning window value prior to or on the same day as the first dose date of atumelnant. Change from baseline was analyzed using the mean at baseline and at each visit, for all participants with both baseline and the corresponding visit values.
Time frame: Baseline and Week 12
Change From Baseline in Morning (Before 11:00) Serum 17-hydroxyprogesterone (17-OHP) AM Dosing
Elevated levels of the immediate enzyme substrate 17-OHP are indicative of CAH. The secondary efficacy endpoint was change from baseline in morning serum 17-OHP at Week 12. Baseline is defined as the last non-missing morning window value prior to or on the same day as the first dose date of atumelnant. Change from baseline was analyzed using the mean at baseline and at each visit, for all participants with both baseline and the corresponding visit values.
Time frame: Baseline and Week 12