Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia (CAHtalyst)

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 is a Phase 3 study to evaluate the efficacy, safety, and tolerability of crinecerfont versus placebo administered for 24 weeks in approximately 165 adult participants with classic CAH due to 21-hydroxylase deficiency. The study consists of a 24-week randomized, double-blind, placebo-controlled period, followed by 1 year of active treatment with crinecerfont. Subsequently, participants may elect to participate in the open-label extension (OLE) period. The duration of participation in the study is approximately 20 months for the core study and will be a variable amount of time per participant for the OLE (estimated to be approximately 3 years).

Study Overview

• Status: Active, not recruiting
• Conditions: Congenital Adrenal Hyperplasia
• Intervention / Treatment: Drug: Placebo; Drug: Crinecerfont

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Neurocrine Clinical Site
  • Vienna, Austria, 1090
    • Neurocrine Clinical Site
• Belgium
  • Brussels, Belgium, 1070
    • Neurocrine Clinical Site
  • Leuven, Belgium, 3000
    • Neurocrine Clinical Site
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Neurocrine Clinical Site
  • Sofia, Bulgaria, 1606
    • Neurocrine Clinical Site
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Neurocrine Clinical Site
• Czechia
  • Hradec Králové, Czechia, 50005
    • Neurocrine Clinical Site
• France
  • Angers, France, 49933
    • Neurocrine Clinical Site
  • Grenoble, France, 38700
    • Neurocrine Clinical Site
  • Le Kremlin-Bicêtre, France, 94270
    • Neurocrine Clinical Site
  • Nantes, France, 44093
    • Neurocrine Clinical Site
  • Paris, France, 75651
    • Neurocrine Clinical Site
  • Paris, France, 75679
    • Neurocrine Clinical Site
• Germany
  • Dresden, Germany, 01307
    • Neurocrine Clinical Site
  • Essen, Germany, 45147
    • Neurocrine Clinical Site
  • Frankfurt, Germany, 60590
    • Neurocrine Clinical Site
  • Leipzig, Germany, 04103
    • Neurocrine Clinical Site
  • Munich, Germany, 80336
    • Neurocrine Clinical Site
• Greece
  • Athens, Greece, 106 76
    • Neurocrine Clinical Site
  • Athens, Greece, 115 27
    • Neurocrine Clinical Site
  • Athens, Greece, 11527
    • Neurocrine Clinical Site
  • Thessaloniki, Greece, 54642
    • Neurocrine Clinical Site
• Israel
  • Afula, Israel, 1834111
    • Neurocrine Clinical Site
  • Beersheba, Israel, 8410101
    • Neurocrine Clinical Site
  • Petah Tikva, Israel, 4941480
    • Neurocrine Clinical Site
  • Tel Aviv, Israel, 64239
    • Neurocrine Clinical Site
• Italy
  • Ancona, Italy, 60126
    • Neurocrine Clinical Site
  • Bologna, Italy, 40138
    • Neurocrine Clinical Site
  • Florence, Italy, 50139
    • Neurocrine Clinical Site
  • Messina, Italy, 98125
    • Neurocrine Clinical Site
  • Milan, Italy, 20132
    • Neurocrine Clinical Site
  • Milan, Italy, 20149
    • Neurocrine Clinical Site
  • Naples, Italy, 80131
    • Neurocrine Clinical Site
  • Padova, Italy, 35128
    • Neurocrine Clinical Site
  • Roma, Italy, 00161
    • Neurocrine Clinical Site
• Netherlands
  • Leiden, Netherlands, 2333
    • Neurocrine Clinical Site
• Poland
  • Krakow, Poland, 31-011
    • Neurocrine Clinical Site
  • Poznan, Poland, 60-355
    • Neurocrine Clinical Site
  • Warsaw, Poland, 01-809
    • Neurocrine Clinical Site
• Portugal
  • Porto, Portugal, 4200-319
    • Neurocrine Clinical Site
• Serbia
  • Belgrade, Serbia, 11000
    • Neurocrine Clinical Site
• Spain
  • Madrid, Spain, 28034
    • Neurocrine Clinical Site
  • Seville, Spain, 41013
    • Neurocrine Clinical Site
• Sweden
  • Gothenburg, Sweden, 41345
    • Neurocrine Clinical Site
  • Stockholm, Sweden, 17176
    • Neurocrine Clinical Site
• United Kingdom
  • Cardiff, United Kingdom, CF14 4HH
    • Neurocrine Clinical Site
  • London, United Kingdom, WC1B 5EH
    • Neurocrine Clinical Site
  • Manchester, United Kingdom, M20 4BX
    • Neurocrine Clinical Site
  • Salford, United Kingdom, M6 8HD
    • Neurocrine Clinical Site
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Neurocrine Clinical Site
    • San Diego, California, United States, 92123
      • Neurocrine Clinical Site
    • San Francisco, California, United States, 94143
      • Neurocrine Clinical Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Neurocrine Clinical Site
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Neurocrine Clinical Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Neurocrine Clinical Site
  • Maryland
    • Bethesda, Maryland, United States, 20982
      • Neurocrine Clinical Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Neurocrine Clinical Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Neurocrine Clinical Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • Neurocrine Clinical Site
    • Rochester, Minnesota, United States, 55905
      • Neurocrine Clinical Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Neurocrine Clinical Site
  • New York
    • Great Neck, New York, United States, 11021
      • Neurocrine Clinical Site
    • New York, New York, United States, 10029
      • Neurocrine Clinical Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Neurocrine Clinical Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • Neurocrine Clinical Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Neurocrine Clinical Site
    • Pittsburgh, Pennsylvania, United States, 15224
      • Neurocrine Clinical Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Neurocrine Clinical Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Neurocrine Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be willing and able to adhere to the study procedures, including all requirements at the study center and return for the follow-up visit.
2. Have a medically confirmed diagnosis of classic CAH due to 21-hydroxylase deficiency.
3. Be on a stable steroid regimen.
4. Participants of childbearing potential must agree to use an acceptable method of contraception during the study.

Exclusion Criteria:

1. Have a diagnosis of any of the other known forms of classic CAH.
2. Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy.
3. Have a clinically significant unstable medical condition or chronic disease other than CAH.
4. Have a history of cancer unless considered cured.
5. Are pregnant.
6. Have a known history of clinically significant arrhythmia or abnormalities on ECG.
7. Have a known hypersensitivity to any corticotropin releasing hormone receptor antagonists.
8. Have received any other investigational drug within 30 days before initial screening or plan to use an investigational drug (other than the study drug) during the study.
9. Have current substance dependence, or current substance (drug) or alcohol abuse.
10. Have had a blood loss ≥550 mL or donated blood or blood products within 8 weeks prior to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crinecerfont; Crinecerfont capsule, administered orally, twice daily for 24 weeks during the placebo-controlled treatment period, followed by active treatment with crinecerfont for at least 1 year.	Drug: Crinecerfont; CRF type 1 receptor antagonist; Other Names: NBI-74788; Crenessity
Placebo Comparator: Placebo; Placebo capsule, administered orally, twice daily for 24 weeks, followed by active treatment with crinecerfont for at least 1 year.	Drug: Placebo; Non-active dosage form; Drug: Crinecerfont; CRF type 1 receptor antagonist; Other Names: NBI-74788; Crenessity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Glucocorticoid Daily Dose at Week 24	Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Serum 17-hydroxyprogesterone (17-OHP) at Week 4	Baseline, Week 4
Change From Baseline in Serum Androstenedione at Week 4	Baseline, Week 4
Number of Participants Who Achieved a Reduction to Physiologic Glucocorticoid Dose While Maintaining Androstenedione Control at Week 24	Week 24
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24	Baseline, Week 24
Percent Change From Baseline in Body Weight at Week 24	Baseline, Week 24
Change From Baseline in Percent Total Fat Mass at Week 24	Baseline, Week 24
Change From Baseline in Blood Pressure at Week 24	Baseline, Week 24
Change From Baseline in Glucose Tolerance at Week 24	Baseline, Week 24
Change From Baseline in Waist Circumference at Week 24	Baseline, Week 24
Change From Baseline in Menstrual Regularity at Week 24	Baseline, Week 24
Change From Baseline in Testicular Adrenal Rest Tumor (TART) Volume at Week 24	Baseline, Week 24

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences
• Investigators: Study Director: Clinical Development Lead, Neurocrine Biosciences

Publications and helpful links

General Publications

• Auchus RJ, Hamidi O, Pivonello R, Bancos I, Russo G, Witchel SF, Isidori AM, Rodien P, Srirangalingam U, Kiefer FW, Falhammar H, Merke DP, Reisch N, Sarafoglou K, Cutler GB Jr, Sturgeon J, Roberts E, Lin VH, Chan JL, Farber RH; CAHtalyst Adult Trial Investigators. Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia. N Engl J Med. 2024 Aug 8;391(6):504-514. doi: 10.1056/NEJMoa2404656. Epub 2024 Jun 1.

Helpful Links

• Study website - CAHtalyst Study

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Actual): July 19, 2023
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: July 24, 2020
• First Submitted That Met QC Criteria: July 24, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• 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; crinecerfont
• Other Study ID Numbers: NBI-74788-CAH3003; 2019-004873-17 (EudraCT Number); 2023-509171-16-00 (Ctis)

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