A Study to Evaluate the Safety and PK of CRN04894 for the Treatment of Cushing's Syndrome

A Phase 1b/2a Open-label Multiple-ascending Dose Exploratory Study of CRN04894 in ACTH-dependent Cushing's Syndrome (Cushing's Disease or Ectopic ACTH Syndrome)

A Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with CRN04894 (an adrenocorticotropic hormone [ACTH] receptor antagonist) in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome [EAS])

Study Overview

• Status: Recruiting
• Conditions: Cushing Syndrome; Cushing Disease; Ectopic ACTH Syndrome
• Intervention / Treatment: Drug: atumelnant

Detailed Description

This is a Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with atumelnant (also known as CRN04894) (an adrenocorticotropic hormone [ACTH] receptor antagonist) over a 10-day or 14-day treatment period in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome [EAS]). Participants will receive oral atumelnant once daily for 10 days followed by monitoring during 4 'wash-out' days, or for 14 days.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Crinetics Clinical Trials; Phone Number: 833-827-9741; Email: clinicaltrials@crinetics.com

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health (NIH) - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      • Contact: Lynnette K Nieman, MD; Phone Number: 301-496-8935; Email: niemanl@nih.gov
      • Contact: Lynnette K Nieman, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult male or female, aged 18 years or more
2. Evidence of chronic 'active' ACTH-dependent Cushing's syndrome
3. Evidence of acutely 'active' ACTH-dependent Cushing's syndrome within 10 days of Day 1
4. Participants with documented ACTH-dependent Cushing's syndrome taking short-acting steroidogenesis inhibitors (ketoconazole, levoketoconazole, osilodrostat, or metyrapone) may participate after a washout period of at least 5 days, if they meet other study inclusion criteria, relative to Investigator's judgment. Participants with documented ACTH-dependent Cushing's syndrome taking cabergoline may participate after a washout period of at least 14 days, if they meet other study inclusion criteria

Exclusion Criteria:

1. Women who are pregnant or lactating
2. History of bilateral adrenalectomy
3. Previous pituitary MRI findings of a putative ACTH-secreting lesion within 3 mm of the optic chiasm
4. Presence of any known malignancy
5. Use of mitotane
6. Previous unsuccessful surgery for Cushing's syndrome within 6 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multiple Ascending Doses; Sequential, open-label, 10-day or 14-day fixed-dose cohorts.	Drug: atumelnant; Atumelnant is an orally active investigational agent which antagonizes the action of ACTH at its receptor administered as oral tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants with treatment emergent adverse events (TEAEs)	Up to Day 15
Proportion of participants with adrenal insufficiency	Up to Day 15
Proportion of participants with safety findings determined by laboratory testing	Up to Day 15
Assessment of the maximum observed plasma concentration of CRN04894	Up to Day 15
Assessment of the time to achieve maximum observed plasma concentration of CRN04894	Up to Day 15
Assessment of the plasma area under the curve of CRN04894	Up to Day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in early morning serum cortisol	Up to Day 15

Collaborators and Investigators

• Sponsor: Crinetics Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: March 27, 2023
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): April 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Cushing Disease; Cushing Syndrome; CRN04894; atumelnant; Ectopic ACTH Syndrome
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Heart Diseases; Neoplasms by Histologic Type; Disease; Arrhythmias, Cardiac; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Adenoma; Paraneoplastic Syndromes; Adrenal Gland Diseases; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Pituitary Neoplasms; Adrenocortical Hyperfunction; Paraneoplastic Endocrine Syndromes; Syndrome; ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion; Cushing Syndrome; Cardiac Complexes, Premature; ACTH Syndrome, Ectopic
• Other Study ID Numbers: CRN04894-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No