Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 in Participants With Congenital Adrenal Hyperplasia (TouCAHn)

A 12-week, Phase 2 Open-label, Sequential Dose Cohort Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 Treatment in Participants With Congenital Adrenal Hyperplasia (TouCAHn)

The purpose of this Phase 2, open-label, sequential dose cohort study is to evaluate the safety, efficacy, and pharmacokinetics (PK) of atumelnant (CRN04894) in participants with classic congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency.

Study Overview

• Status: Completed
• Conditions: Congenital Adrenal Hyperplasia; Classic Congenital Adrenal Hyperplasia
• Intervention / Treatment: Drug: atumelnant (CRN04894)

Detailed Description

This Phase 2, open-label, sequential dose cohort study will evaluate the efficacy, safety, PK, and PD of atumelnant (CRN04894) when administered for 12 weeks in participants with CAH caused by 21-hydroxylase deficiency. Up to 42 participants will be enrolled in the study.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1180
    • Crinetics Study Site
  • Córdoba Province
    • Córdoba, Córdoba Province, Argentina, 5000
      • Crinetics Study Site
• Brazil
  • Rio de Janeiro, Brazil, 20231-092
    • Crinetics Study Site
  • Rio de Janeiro, Brazil, 20551-030
    • Crinetics Study Site
  • São Paulo, Brazil, 05403-000
    • Crinetics Study Site
  • São Paulo, Brazil, 04024-002
    • Crinetics Study Site
  • Paraná
    • Curitiba, Paraná, Brazil, 80030-110
      • Crinetics Study Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90410-000
      • Crinetics Study Site
  • São Paulo
    • Botucatu, São Paulo, Brazil, 18618-686
      • Crinetics Study Site
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Crinetics Study Site
• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80336
      • Crinetics Study Site
• India
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • Crinetics Study Site
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632004
      • Crinetics Study Site
• Italy
  • Naples, Italy, 80131
    • Crinetics Study Site
  • Roma, Italy, 00161
    • Crinetics Study Site
  • Rozzano, Italy, 20089
    • Crinetics Study Site
• United Kingdom
  • London, United Kingdom, NW1 2PG
    • Crinetics Study Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2RX
      • Crinetics Study Site
  • West Midlands
    • Coventry, West Midlands, United Kingdom, CV22DX
      • Crinetics Study Site
• United States
  • California
    • Pasadena, California, United States, 91105
      • Crinetics Study Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Crinetics Study Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • Crinetics Study Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Crinetics Study Site
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Crinetics Study Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Crinetics Study Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Crinetics Study Site
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Crinetics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participants ≥18 to 75 years of age at the time of signing the Informed Consent Form (ICF). Participants ≥16 years of age may be included in sites located in the United States
2. Classic 21-hydroxylase deficiency
3. On a stable regimen of glucocorticoid replacement (eg, hydrocortisone, prednisolone, prednisone, methylprednisolone)
4. Compliance with glucocorticoid replacement and mineralocorticoid replacement (if applicable) regimen during the Screening Period
5. Minimum total daily dose of ≥15 mg hydrocortisone (or equivalent). For Cohort 4, a mean daily dose of ≥11 mg/m²/day of hydrocortisone or hydrocortisone equivalents will be used for inclusion
6. If on estrogen therapy (any route), dose must be stable for at least 3 months prior to Screening

Exclusion Criteria:

1. Diagnosis of any other form of CAH other than classic 21-hydroxylase deficiency
2. Dexamethasone use within 30 days of Screening for Cohorts 1-3. In Cohort 4, dexamethasone is permitted
3. History of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy
4. Night shift workers or any other reason for abnormal sleep/wake cycles
5. Clinically significant unstable medical condition or chronic disease other than CAH
6. History of major surgery/surgical therapy for any cause within 4 weeks prior to Screening
7. Diabetes mellitus treated with insulin for less than 6 weeks prior to Screening, or with change in total daily insulin dose by >15% within 6 weeks prior to Screening
8. Poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5%(≥69 mmol/mL), or estimated HbA1c based on fructosamine if HbA1c is not evaluable (eg, due to hemoglobinopathies)
9. Participants with hypothyroidism who are not receiving adequate hormone replacement therapy based on thyroid hormone levels measured at the time of Screening
10. History of unstable angina or acute myocardial infarction within 12 weeks prior to Screening or other clinically significant cardiac disease at the time of Screening
11. History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ
12. Pregnant or lactating
13. Known history of illicit drug or alcohol abuse within the last year
14. Use of antiandrogen therapy in the past 3 months (eg, spironolactone, finasteride, cyproterone acetate, flutamide)
15. Use of testosterone, androgen-containing supplements, aromatase inhibitors, or growth hormone

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: Sequential Dose; Sequential, open-label, 12-week fixed-dose cohorts.	Drug: atumelnant (CRN04894); Atumelnant is an orally active nonpeptide melanocortin 2 receptor (MC2R) or adrenocorticotropic hormone (ACTH) antagonist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Morning (Before 11:00) Serum Androstenedione (A4) PM Dosing	A4 is the principal biochemical measure of disease activity in adult CAH. Blood samples were collected for the measurement of serum concentration of A4 prior to glucocorticoid administration. Baseline is defined as the last non-missing morning window value prior to or on the same day as the first dose date of atumelnant. Change from baseline was obtained by subtracting post-baseline visit value minus baseline value.	Baseline and Week 12
Change From Baseline in Morning (Before 11:00) Serum Androstenedione (A4) AM Dosing	A4 is the principal biochemical measure of disease activity in adult CAH. Blood samples were collected for the measurement of serum concentration of A4 prior to glucocorticoid administration. Baseline is defined as the last non-missing morning window value prior to or on the same day as the first dose date of atumelnant. Change from baseline was obtained by subtracting post-baseline visit value minus baseline value.	Baseline and Week 12
Number of Participants Reporting of Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events Leading to Discontinuation Throughout the Study	An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. TEAEs were collected in the full analysis set which consisted of all participants who received at least one dose of study drug. A serious AE is defined by its severe clinical consequences: it is any event that results in death, is life-threatening, requires inpatient hospitalization, results in persistent disability, or requires medical intervention to prevent these outcomes.	From Day 1 to Up to Week 16 (End of study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Morning (Before 11:00) Serum 17-hydroxyprogesterone (17-OHP) PM Dosing	Elevated levels of the immediate enzyme substrate 17-OHP are indicative of CAH. The secondary efficacy endpoint was change from baseline in morning serum 17-OHP at Week 12. Baseline is defined as the last non-missing morning window value prior to or on the same day as the first dose date of atumelnant. Change from baseline was analyzed using the mean at baseline and at each visit, for all participants with both baseline and the corresponding visit values.	Baseline and Week 12
Change From Baseline in Morning (Before 11:00) Serum 17-hydroxyprogesterone (17-OHP) AM Dosing	Elevated levels of the immediate enzyme substrate 17-OHP are indicative of CAH. The secondary efficacy endpoint was change from baseline in morning serum 17-OHP at Week 12. Baseline is defined as the last non-missing morning window value prior to or on the same day as the first dose date of atumelnant. Change from baseline was analyzed using the mean at baseline and at each visit, for all participants with both baseline and the corresponding visit values.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Crinetics Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2023
• Primary Completion (Actual): August 22, 2025
• Study Completion (Actual): August 22, 2025

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: June 8, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Congenital Adrenal Hyperplasia; CAH; TouCAHn; CRN04894; atumelnant
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Gonadal Disorders; Congenital Abnormalities; Adrenal Gland Diseases; Disorders of Sex Development; Urogenital Abnormalities; Steroid Metabolism, Inborn Errors; Adrenogenital Syndrome; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Adrenal Hyperplasia, Congenital
• Other Study ID Numbers: CRN04894-03; 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation); 2023-503488-40-00 (Other Identifier: European Medicines Agency)

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