A Study to Evaluate Atumelnant in Adults With Congenital Adrenal Hyperplasia

Not Applicable

Not yet recruiting

• Conditions: Congenital Adrenal Hyperplasia; Classic Congenital Adrenal Hyperplasia
• Interventions: Drug: Atumelnant; Drug: Placebo

• Registration Number: NCT07144163
• Lead Sponsor: Crinetics Pharmaceuticals Inc.

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, PK, and PD of atumelnant in adults with classic CAH due to 21-OHD.

Detailed Description

This is a Phase 3, global, multicenter, randomized, double-blind, placebo-controlled study in adult participants (male or female age ≥18 to \<75 years) with classic CAH due to 21-OHD who have been on a stable regimen of GCs for at least 2 months to evaluate efficacy, safety, PK, and PD of atumelnant administered once per day. Following a 3- to 6-week Screening Period, eligible participants will enter the Treatment Period where they will be randomly assigned in a 2:1 ratio to receive either atumelnant 80 mg once daily (with an option for dose escalation to 120 mg once daily at Week 20) or placebo.

A total of approximately 150 participants may be enrolled in the study.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-20
• Study First Submitted QC: 2025-08-20
• Study First Posted: 2025-08-27
• Last Update Submitted: 2025-08-29
• Study Start: 2025-09-01
• Last Update Posted: 2025-09-05
• Primary Completion: 2027-05
• Study Completion: 2027-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Male or female, between ≥18 to <75 years of age at the time of signing the ICF.

2. Willing and able to understand and adhere to the study procedures as specified in the protocol and comply with the study treatment.

3. Have classic CAH due to 21-OHD confirmed by the Investigator and approved by the Medical Monitor.

4. Participants with levels of morning serum A4 as follows:

   • A4 >ULN and treated with <11 mg/m2/day (physiologic) GC doses
   • OR normal A4 (above mid-range to ≤ULN) and treated with ≥15 mg/m2/day GC doses
   • OR A4 >ULN and treated with ≥11 mg/m2/day GC doses.

5. On a stable (defined as no dose change of >5 mg/day hydrocortisone equivalent within 2 months prior to Screening) regimen of GC replacement (e.g., hydrocortisone, prednisolone, prednisone, methylprednisolone, meprednisone, dexamethasone, cortisone acetate) at the time of informed consent.

6. If treated with mineralocorticoids (fludrocortisone), the dose should be stable for at least 2 months prior to Screening without orthostatic hypotension, and with serum sodium and potassium in the normal range.

7. If on estrogen therapy (any route), the dose must be stable for at least 3 months prior to Screening.

Exclusion Criteria

1. Diagnosis of any form of CAH other than classic 21-OHD.
2. History of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic GC therapy.
3. Clinically significant medical condition or abnormal laboratory tests, as judged by the Investigator, other than CAH.
4. Concomitant mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study, and/or evidence of poor compliance with medical instructions.
5. History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ.
6. Women who are pregnant or lactating or, if of childbearing potential, who are unwilling to use highly effective contraception as described in this study. Male participants who are unwilling to use highly effective contraception as described in this study.
7. Known history of, or concern for, risk of hypersensitivity reaction to atumelnant or any of its excipients.
8. Participants with an increased risk of developing adrenal insufficiency as judged by the Investigator.
9. Severe erythrocytosis as judged by the Investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment	Atumelnant	Atumelnant tablet, administered orally, once daily for 32 weeks.
Placebo	Placebo	Matching placebo, administered orally, once daily for 32 weeks.

Primary Outcome Measures

Name	Time	Method
Proportion of participants with morning post-GC A4 ≤ ULN who are on physiologic GC replacement.	Week 32

Secondary Outcome Measures

Name	Time	Method
Percent change from baseline of morning pre-GC A4	Week 2
Percent change from baseline of morning pre-GC 17-OHP	Week 32
Proportion of participants with morning pre-GC A4 ≤ ULN who are on physiologic GC replacement	Week 32
Percent change from baseline in GC daily dose when morning post-GC A4 ≤ ULN	Week 32

Trial Locations

Locations (1)

Crinetics Study Site; 🇦🇺 Nedlands, Western Australia, Australia