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

Cushing Syndrome Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05804669
• Other study ID #: CRN04894-04
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 12, 2023
• Est. completion date: October 2026

Study information

• Verified date: January 2024
• Source: Crinetics Pharmaceuticals Inc.
• Contact: Crinetics Clinical Trials
• Phone: 833-827-9741
• Email: clinicaltrials[@]crinetics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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])

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 CRN04894 (an adrenocorticotropic hormone [ACTH] receptor antagonist) over a 10-day treatment period in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome [EAS]).Participants will receive oral CRN04894 once daily for 10 days, followed by monitoring during 4 'wash-out' days.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: October 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female, aged 18-75 years

2. Evidence of 'active' ACTH-dependent Cushing's syndrome within 14 days of Day 1

3. Participants with documented ACTH-dependent Cushing's syndrome taking short-acting steroidogenesis inhibitors (ketoconazole, levoketoconazole, osilodrostat, cabergoline or metyrapone) may participate after a 14-day washout period, 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. A UFC more than 8-fold ULN

6. Use of mitotane

7. Previous unsuccessful surgery for Cushing's syndrome within 6 weeks

Related Conditions & MeSH terms

• ACTH-Secreting Pituitary Adenoma
• Cushing Disease
• Cushing Syndrome
• Ectopic ACTH Syndrome
• Pituitary ACTH Hypersecretion
• Syndrome

Intervention

Drug:
• CRN04894
CRN04894 is an orally active investigational agent which antagonizes the action of ACTH at its receptor administered as oral tablets.

Locations

Country	Name	City	State
United States	National Institutes of Health (NIH) - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Crinetics Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with treatment emergent adverse events (TEAEs)		Up to Day 15
Primary	Proportion of participants with adrenal insufficiency		Up to Day 15
Primary	Proportion of participants with safety findings determined by laboratory testing		Up to Day 15
Primary	Assessment of the maximum observed plasma concentration of CRN04894		Up to Day 15
Primary	Assessment of the time to achieve maximum observed plasma concentration of CRN04894		Up to Day 15
Primary	Assessment of the plasma area under the curve of CRN04894		Up to Day 15
Secondary	Change from baseline in early morning serum cortisol		Day 11