Clinical trial NCT05804669: A Study to Evaluate the Safety and PK of CRN04894 for the Treatment of Cushing's Syndrome
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cushing Syndrome
Cushing Disease
Ectopic ACTH Syndrome
Keywords: Cushing Syndrome
Cushing Disease
Ectopic ACTH Syndrome
CRN04894
atumelnant
Lead sponsor: Crinetics Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2023-04-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants with treatment emergent adverse events (TEAEs)
timeFrame: Up to Day 15
measure: Proportion of participants with adrenal insufficiency
timeFrame: Up to Day 15
measure: Proportion of participants with safety findings determined by laboratory testing
timeFrame: Up to Day 15
measure: Assessment of the maximum observed plasma concentration of CRN04894
timeFrame: Up to Day 15
measure: Assessment of the time to achieve maximum observed plasma concentration of CRN04894
timeFrame: Up to Day 15
measure: Assessment of the plasma area under the curve of CRN04894
timeFrame: Up to Day 15
Secondary outcomes:
measure: Change from baseline in early morning serum cortisol
timeFrame: Up to Day 15
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health (NIH) - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
state: Maryland
Study officials:
References: