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

Crinetics Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Ectopic ACTH Syndrome; Cushing Disease; Cushing Syndrome

Treatments: Drug: atumelnant

Study type: Interventional

Funder types: Industry

Identifiers

NCT05804669

CRN04894-04

Details and patient eligibility

About

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])

Full 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.

Enrollment: 18 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Multiple Ascending Doses

Experimental group

Description:

Sequential, open-label, 10-day or 14-day fixed-dose cohorts.

Treatment:

Drug: atumelnant