None listed
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of atumelnant in participants with ADCS. This entire study consists of 3 parts: Part A (not described in this registration), Part B (not described in this registration), and Part C. In Part C is an open-label long-term portion of the study. All participants will receive atumelnant by mouth for up to 2 years, using a concomitant B&R treatment regimen. Up to 201 participants will be included (up to 186 from Parts A and B, and approximately 15 new participants).
Interventions
Intervention: Atumelnant (CRN04894) A potent and selective orally administered nonpeptide small molecule melanocortin 2 receptor (MC2R) competitive antagonist under development for the treatment of ACTH-Dependent Cushing’s syndrome and congenital adrenal hyperplasia. Atumelnant is provided as a film coated tablet for oral use. Participant IP compliance will be monitored through an electronic clinical outcome assessment (eCOA system) requiring real-time documentation of dosing and administration, with ongoing review to assess adherence. Participants will bring the study drugs on their visits so the study doctor can monitor the intake. Intervention Model: Part C: Open-label extension, single arm. Part C will enroll 3 groups of participants: - Group 1: Participants who completed either Part A or B of the study. - Group 2: When Part B enrollment closes, any participants in screening for Part B who are deemed eligible for the study will have the opportunity to enroll in Part C. - Group 3: Enrollment for participants with severe ADCS or cyclic ADCS occurs once an effective dose of atumelnant is determined in Part A. In Part C, all participants will be assigned to atumelnant. All participants in the open-label part of the study, irrespective of prior treatment assignment, will initiate treatment with 80mg of atumelnant (or an alternative dose recommended by the Data Monitoring Committee) for up to 2 years. Participants with severe ADCS may receive 120 mg of atumelnant. The standard B&R strategy in the treatment of ADCS involves inhibiting cortisol synthesis until the point of hypoadrenalism and replacing it with physiological dose of glucocorticoid (GC) replacement therapy.
Sponsors
Crinetics Pharmaceuticals, Inc.
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
Part C: Group 1: -Part A Arm 1: Complete the 12-week Treatment Period on study drug or standard of care medication, or enter the OLE during the Week 6 evaluation using Guidance to the Investigator for Part A Arm 1, or are rescued due to hypercortisolism and, in the Investigator’s opinion, would benefit from participation in the OLE. -Part A Arms 2, 3, and 4: Complete the 12-week Treatment Period on study drug or standard of care medication and, in the Investigator’s opinion, would benefit from participation in the OLE. -Part B: Complete the 12-week Treatment Period on study drug or standard of care medication and, in the Investigator’s opinion, would benefit from participation in the OLE. Group 2: Participants must meet Part B inclusion criteria*. Group 3: New participants entering must meet the same inclusion criteria as Parts A and B with the exception that individuals with severe ADCS or cyclic ADCS are allowed*. *Part A and B inclusion criteria: - Male or female, between 18 up to and including 74 years of age at the time of signing the ICF. Participants from 16 years of age may be included at sites located in the US. - Participants must have confirmed ADCS. (Part C Group 3 only: protocol-defined cyclic or severe ADCS.) - Morning plasma ACTH greater than 10 pg/mL during screening confirmed by the central laboratory and available prior to randomization on Day 1. - Participants with de novo Cushing’s disease (pituitary Cushing’s syndrome), ectopic ACTH syndrome (EAS), or ADCS of uncertain etiology who are not eligible for surgery (eg, poor surgical candidates, surgically unapproachable tumors, who refuse to have surgical treatment, or surgical treatment is not available) and could benefit from chronic treatment with study drug for at least 4 months.
Exclusion criteria
Group 1: Individuals in Part A or B who do not meet Part C inclusion criteria. Group 2: Individuals who meet any Part B exclusion criterion*. Group 3: New participants who meet any of the exclusion criteria for Part A and Part B*. *Part A and B exclusion criteria: - Use of some medications could lead participants to enter the Washout Period. - History of bilateral adrenalectomy. - History of major surgery within 1 month prior to screening. - Pituitary surgery within 3 months of Day 1. - Participants who received pituitary irradiation within 2 years (stereotactic radio surgery) or 3 years (conventional radiation) before enrolment (Day 1). - Participants who have previously taken atumelnant. - Participants who will not benefit from chronic treatment with study drug or have a life expectancy of less than 6 months. - Clinically significant concomitant disease considered by the Investigator likely to affect safe participation in the study.
Outcome results
None listed