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

Phase 1

Recruiting

• Conditions: Cushing Syndrome; Cushing Disease; Ectopic ACTH Syndrome
• Interventions: Drug: CRN04894

• Registration Number: NCT05804669
• Lead Sponsor: Crinetics Pharmaceuticals Inc.

Brief 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 \[EAS\])

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 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.

Study Timeline

• Study First Submitted: 2023-03-27
• Study First Submitted QC: 2023-03-27
• Study First Posted: 2023-04-07
• Study Start: 2023-10-12
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-24
• Last Update Posted: 2024-07-26
• Primary Completion: 2026-10
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18

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, cabergoline or metyrapone) may participate after a 14-day washout period, if they meet other study inclusion criteria

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Multiple Ascending Doses	CRN04894	Sequential, open-label, 10-day fixed-dose cohorts.

Primary Outcome Measures

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

Name	Time	Method
Change from baseline in early morning serum cortisol	Day 11

Trial Locations

Locations (1)

National Institutes of Health (NIH) - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); 🇺🇸 Bethesda, Maryland, United States