Atumelnant for Congenital adrenal hyperplasia

Inclusion criteria

• {"criterion_text":"-1. Participants with CAH who have completed a Crinetics CRN04894 study or completed treatment in a Crinetics CRN04894 study, and in the opinion of the Investigator had an acceptable benefit-risk assessment in the completed study and would benefit from continued dosing in this extension study: a. Group 1: Participants meeting the above criteria and are currently receiving CRN04894. b. Group 2: Participants meeting the above criteria and are not currently receiving CRN04894. Note: The maximum dose of CRN04894 in this study is not to exceed the maximum dose in a parent study for the indication."}
• {"criterion_text":"-2. Participants must be compliant, in the opinion of the Investigator, with a stable regimen of glucocorticoid replacement (eg, hydrocortisone, prednisolone, prednisone, methylprednisolone), and a minimum total daily dose of ≥XX mg hydrocortisone (HC) or equivalent at the time of Informed Consent."}
• {"criterion_text":"-3. Female participants who engage in heterosexual intercourse must: a. Be of nonchildbearing potential, defined as either surgically sterile (ie, hysterectomy, bilateral salpingectomy, tubal ligation for at least 3 months, or bilateral oophorectomy), OR b. Be postmenopausal with at least 1 year of amenorrhea. In participants with less than 1 year of amenorrhea, confirmation is required with 2 follicle-stimulating hormone (FSH) measurements. A documented, historical test result measured prior to Screening may be used as 1 of the 2 measurements. The FSH value should be ≥30 IU/L to confirm menopausal status, OR c. Agree to use a highly effective method of contraception from the beginning of Screening until at least 2 weeks after the last dose of study drug. Contraceptive use by men and women also should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Periodic abstinence (ie, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception."}
• {"criterion_text":"-4. Male participants agree to use a condom when sexually active with a female partner of childbearing potential from Screening until at least 2 weeks after the last dose of study drug (or be surgically sterile [ie, vasectomy with a confirmed absence of sperm in ejaculate]; or agree to remain abstinent on a long-term and persistent basis). Male participants should also agree to not donate sperm for the duration of the study and until at least 2 weeks after the last dose of study drug."}
• {"criterion_text":"-5. Participant are willing and able to give signed informed consent, including compliance with the requirements and restrictions listed in the Informed Consent Form (ICF)."}
• {"criterion_text":"-6. Participants are willing and able to comply with the study procedures as specified in the protocol and comply with the study treatment."}

Exclusion criteria

• {"criterion_text":"-1. Any medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardize the participant’s safety or ability to complete the study."}
• {"criterion_text":"-10. Specific for Participants in Group 2: 10. Participants with any clinically significant abnormal laboratory test during Screening or clinically significant concomitant disease other than CAH including but not limited to cardiovascular disease; moderate or severe renal insufficiency (estimated glomerular filtration rate <60 mL/min/1.73 m2 using Chronic Kidney Epidemiology Collaboration [CKD-EPI] formula) at Screening; or Significant liver disease or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3× upper limit of normal (ULN), and/or total bilirubin >1.5×ULN during Screening. Participants with previously diagnosed Gilbert’s syndrome not accompanied by other hepatobiliary disorders and associated with total bilirubin <3.5 mg/dL (<51.3 μmol/L) will be permitted."}
• {"criterion_text":"-11. Participants with a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy."}
• {"criterion_text":"-12. Participants with a history of major surgery/surgical therapy for any cause within 4 weeks prior to Screening."}
• {"criterion_text":"-13. Participants with poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5% (≥69 mmol/mL)."}
• {"criterion_text":"-14. Participants with hypothyroidism who are not receiving adequate hormone replacement therapy based on thyroid hormone levels measured at the time of Screening, as determined by the Investigator."}
• {"criterion_text":"-15. Participant has an average (of 3 electrocardiograms [ECGs]) Fridericia’s corrected QT (QTcF) interval >450 milliseconds (msec) (men) or >470 msec (women), time interval between P and R waves (PR interval) >220 msec, time interval of the QRS complex (QRS) interval >120 msec, second- or third-degree atrioventricular block, left bundle branch block, or hemiblock at Screening."}
• {"criterion_text":"-2. Participants have known history of (that is within the past 12 months), or current alcohol or drug abuse."}
• {"criterion_text":"-3. Participants have any 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."}
• {"criterion_text":"-4. Participants have a known allergy or hypersensitivity to any of the test materials or related compounds, including being at high risk of adrenal insufficiency as judged by the Investigator."}
• {"criterion_text":"-5. 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."}
• {"criterion_text":"-6. Participant is an employee or immediate family member of an employee of Crinetics."}
• {"criterion_text":"-7. Participants who have been dosed with an investigational drug (other than CRN04894) in any prior clinical study within 60 days or 5 half-lives (whichever is longer) prior to informed consent or plan to use an investigational drug in another study."}
• {"criterion_text":"-8. Participants with a history of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ."}
• {"criterion_text":"-9. Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities."}

Primary endpoints

• {"endpoint_text":"-Primary Safety Endpoints: Incidence of treatment-emergent adverse events (TEAEs), including treatment-emergent serious adverse events (SAEs) and any adverse events (AEs) leading to discontinuation Incidence of glucocorticoid (GC) deficiency/adrenal insufficiency and adrenal crisis Incidence of hospitalizations related to congenital adrenal hyperplasia (CAH) Primary Efficacy Endpoint: Change from baseline in morning (before 11:00 AM) serum A4 over time","definition_or_measurement_approach":"Safety: measured as incidence counts of TEAEs, treatment-emergent SAEs, AEs leading to discontinuation, incidence of GC deficiency/adrenal insufficiency/adrenal crisis, and hospitalizations related to CAH. Efficacy: change from baseline in morning (before 11:00 AM) serum androstenedione (A4) measured over time."}

Secondary endpoints

• {"endpoint_text":"-Secondary Efficacy Endpoints Change from baseline in morning (before 11:00 AM) serum 17-OHP over time Change from baseline in daily GC dose (hydrocortisone [HC] mg equivalents) over time","definition_or_measurement_approach":"Efficacy: change from baseline in morning (before 11:00 AM) serum 17-hydroxyprogesterone (17-OHP) measured over time; change from baseline in daily glucocorticoid dose expressed as hydrocortisone (HC) mg equivalents measured over time."}

Germany

Earliest CTIS Part Ii Submission Date

16-01-2025

Latest Decision Or Authorization Date

12-11-2025

Processing Time Days

300

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

06-03-2025

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

252

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Crinetics Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

codes: 1,11,12,13,2,5,8

Name

Suvoda LLC

Responsibilities

code: 3 (data capture/clinical trial technology vendor)

Name

Everest Clinical Research Corporation

Responsibilities

code: 7 (site management/other CRO duties)

Third parties

• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"codes: 1,11,12,13,2,5,8","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"LabConnect Europe B.V.","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"LabConnect GmbH","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Pharmaron (Germantown) Lab Services Inc.","duties_or_roles":"codes: 15 (PK), 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"LabConnect GmbH (Frankfurt Am Main)","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"LabConnect Europe B.V. (Swalmen)","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labconnect LLC","duties_or_roles":"codes: 15 (Safety-related labs (urine) - sample staorage), 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"code: 15 (Imaging)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Labor Berlin Charite Vivantes GmbH","duties_or_roles":"code: 15 (17OHP, A4, Testosterone, Aldosterone, Progesterone, 11-DOC, 21 deoxycortisol), 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"code: 7","organisation_type":"Pharmaceutical company"}