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, and Part C (not described in this registration). In Part B of the study, participants will be randomized into 2 arms: - Atumelnant and steroid medication. The atumelnant dose will be determined based on data from Part A. - Placebo atumelnant and placebo steroid. Participants will be randomized in a 2 to 1 ratio (for every 2 participants who receive atumelnant, 1 participant will receive placebo) and will receive the study drug (atumelnant or placebo) by mouth for 12 weeks. Whether a participant receives atumelnant or placebo will be determined by chance (like drawing straws). This part of the study is double blind, the participant, their caregiver(s), and the study doctors will not know which treatment is being given (blinded to treatment). After participation in Part B of the study, participants might be able to stay in the study in Part C (open-label extension where all participants will receive atumelnant and steroid replacement therapy) if, in the Investigator’s opinion, they would benefit from it.
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 B: Randomized, double-blind, parallel arms The 2 arms in Part B will comprise: - a treatment/glucocorticoid (GC) arm at an atumelnant dose recommended by the Data Monitoring Committee (DMC) based on data from Part A of the study (40 mg, 80 mg, or 120 mg) - a placebo/placebo arm. Participants will be randomized 2:1 (atumelnant/GC:placebo/placebo) and will receive the study drug (atumelnant or placebo) by mouth for 12 weeks. Participants will be treated using a concomitant Block & Replace (B&R) treatment strategy receiving simultaneous initiation of atumelnant/GC or placebo/GC placebo administration. 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 GC replacement therapy.
Sponsors
Crinetics Pharmaceuticals, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 74 Years
Healthy volunteers
No
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. - 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
- 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