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Protocol Details

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Crinecerfont (NBI-74788) in Adult Subjects with Classic Congenital Adrenal Hyperplasia, Followed by Open-Label Treatment

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Child Health and Human Development (NICHD)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 18 Years
Max Age: 99 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women;
Non-English Speaking;


excess androgen;
adrenal adrogren;
Corticotropin Releasing Hormone

Recruitment Keyword(s)



Congenital Adrenal Hyperplasia;
excess androgens

Investigational Drug(s)


Investigational Device(s)



Drug: Crinecerfont
Other: Placebo

Supporting Site

National Institute of Child Health and Human Development


People with classic congenital adrenal hyperplasia (CAH) do not make enough of some hormones and make too much of others. People with classic CAH need to take steroids for their entire life, but steroids can cause side effects. Researchers want to see if a new drug, called crinecerfont, can help.


To test a new treatment for CAH and to find out if taking it can lower the amount of steroid medicines that need to be taken.


People aged 18 and older with classic CAH who have been on a stable regimen of glucocorticoid and fludrocortisone (if applicable) for at least 30 days.


Participants will be screened with a medical history and physical exam. They will have an electrocardiogram. They will complete mental health assessments. They will record their daily glucocorticoid doses and (if applicable) the days of their menstrual cycle in an electronic diary.

Participants will have a glucose tolerance test. They will drink a sugary drink with timed blood samples before and after the drink.

Participants will give blood and urine samples. They may collect urine at home.

Participants will complete questionnaires about their health, fatigue, mental well-being, and sleep.

Participants will have a bone density scan of the hip bone, lower spine, and whole body.

Male participants will have a testicular ultrasound.

Participants will take the study drug or placebo as capsules by mouth, 2 times a day, for 6 months. Then they will take the study drug for 6-12 months.

Participation will last for up to 20 months. They will have up to 21 study visits.

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Five subjects, female or male at least 18 years of age, with a documented medically confirmed diagnosis of classic 21-hydroxylase deficiency CAH due to 21-hydroxylase deficiency. Subjects must meet all inclusion criteria and no exclusion criteria to participate.

Subject Inclusion Criteria

To participate in this study, subjects must meet the following criteria:

1. Subjects must provide written informed consent.

2. Be a female or male at least 18 years of age.

3. Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency CAH based on standard medically accepted criteria such as elevated 17-OHP level, confirmed CYP21A2 genotype, positive newborn screening with confirmatory second-tier testing, or cosyntropin stimulation.

4. Be on a stable, supraphysiologic glucocorticoid dose regimen (defined as >13 mg/m2/day in hydrocortisone dose equivalents) that has been stable for at least 1 month prior to screening, is intended for chronic use, and consists of 1 or more of the following orally administered glucocorticoids: hydrocortisone, prednisone, prednisolone, methylprednisolone, or dexamethasone

5. If treated with fludrocortisone, dose should be stable for at least 1 month prior to screening with an upright plasma renin activity (PRA) during screening that is not greater than ULN on the subject s usual sodium intake. If PRA is >ULN, the subject must have systolic blood

pressure >100 mmHg, without orthostatic hypotension, and with serum sodium and potassium in the normal range.

6. Female subjects of childbearing potential with fertile male partners must agree to use contraception consistently from screening until the final study visit or 30 days after the last dose of study drug, whichever is longer. A subject who is not of childbearing potential must

meet one of the following:

-Postmenopausal, defined as no menses for 12 months without an alternative medical cause and confirmed by elevated follicle-stimulating hormone (FSH) consistent with a postmenopausal range.

-Permanent sterilization procedure, such as hysterectomy, bilateral salpingectomy, or bilateral oophorectomy

Acceptable methods of contraception are listed.

Subject Exclusion Criteria

Subjects will be excluded from the study if they meet any of the following criteria:

1. Have a known or suspected diagnosis of any of the other forms of classic CAH including 11-beta-hydroxylase deficiency, 17-alpha-hydroxylase deficiency, 3-beta-hydroxysteroid dehydrogenase deficiency, P450 side-chain cleavage deficiency, or P450 oxidoreductase deficiency.

2. Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic therapy with oral glucocorticoids, or requiring chronic therapy with inhaled glucocorticoids that based on dose and hormone profile the investigator deems would yield

significant systemic exposure interfering with study endpoints.

3. Evidence of glucocorticoid overtreatment during screening, as evidenced by preglucocorticoid morning 17-OHP less than the ULN, post-glucocorticoid morning 17-OHP less than the lower limit of normal, or morning androstenedione level less than the lower limit of normal, based on normal ranges for age and sex.

4. At increased risk of developing adrenal crisis in the Investigator s opinion, based on, for example, repeated history of adrenal crisis in the past, prior history of adrenal crisis precipitated by reducing glucocorticoid dose, recent episode(s), etc.

5. Have a clinically significant medical condition or chronic disease (including history of neurological, hepatic, renal, cardiovascular, gastrointestinal, significant malabsorption, hematologic, pulmonary, psychiatric, or endocrine disease [excluding CAH]) that in the

opinion of the investigator would preclude the subject from participating in and completing the study or that could confound interpretation of study outcome.

6. History of malignancy, unless successfully treated with curative intent and considered to be cured.

7. Have a known history of clinically concerning cardiac arrhythmia (including long QT syndrome) or prolongation of screening (pre-treatment) QT interval corrected for heart rate using Fridericia s correction (QTcF) of >450 msec (males) or >470 msec (females).

8. Known sensitivity (ie, hypersensitivity) or allergy to any corticotropin-releasing hormone (CRH) receptor antagonist.

9. Have evidence of chronic renal or liver disease based on any of these screening laboratory test abnormalities:

-Serum creatinine >1.5 (SqrRoot) ULN.

-Aspartate aminotransferase (AST) >3 (SqrRoot) ULN.

-Alanine aminotransferase (ALT) >3 (SqrRoot) ULN.

-Total bilirubin >1.5 (SqrRoot) ULN unless due to a documented diagnosis of Gilbert's syndrome.

10. Have any of the following hematologic abnormalities at screening:

-Hemoglobin <10 g/dL.

-White blood cell (WBC) count <3.0 (SqrRoot) 103/mm3.

-Platelet count <100,000/mm3.

-Absolute neutrophil count <1.0 (SqrRoot) 103/mm3.

11. Have any of the following coagulation abnormalities at screening:

-Activated partial thromboplastin time (aPTT) that exceeds ULN values by more than 5 seconds.

-Prothrombin time (PT) expressed as international normalized ratio (INR) >1.3, unless the subject is on anticoagulant treatment that affects INR.

12. Used any active investigational drug in the context of a clinical trial within 30 days or 5 half-lives (whichever is longer) before screening, or plans to use such an investigational drug (other than the study drug) during the study.

13. Are using any excluded concomitant medication and cannot discontinue use of these medications for the duration of the study

-Orally administered glucocorticoids for indications other than CAH.

-Strong inducers of CYP3A4 or CYP2B6 except topically administered medications.

-Medications that affect cortisol or glucocorticoid metabolism (eg, phenytoin, mitotane, phenobarbital, strong CYP3A4 inhibitors such as ketoconazole, clarithromycin, cholestyramine, certain antivirals) except topically administered medications.

-Aromatase inhibitors (eg, anastrozole, letrozole, testolactone).

14. Has current substance dependence or substance or alcohol abuse (drugs including controlled substance or non-prescribed use of prescription drugs; nicotine and caffeine dependence are not exclusionary).

15. Have a significant risk of suicidal or violent behavior. Subjects with any suicidal ideation of type 4 (active suicidal ideation with some intent to act, without specific plan) or type 5 (active suicidal ideation with specific plan and intent) in the past 6 months before screening

or any history of suicidal behavior within the past year based on the Columbia-Suicide Severity Rating Scale (C-SSRS) should be excluded.

16. Have had a blood loss greater than or equal to 550 mL or donated blood or blood products within 8 weeks before Day 1 (baseline).

17. Females who are pregnant or lactating.

18. In the Investigator s opinion, the subject is not capable of adhering to the protocol requirements.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Deborah P. Merke, M.D.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CRC BG RM 3-2740
(301) 496-0718

Lee Antoinette J. Keener, C.R.N.P.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CRC BG RM 3-2740
(301) 451-9102

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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