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

NCT04490915 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: NBI-74788-CAH30032019-004873-172023-509171-16-00
• Study Type: interventional
• Target: 182
• Locations: 17 countries
• Sites: 68

Brief Summary

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).

Conditions

Congenital Adrenal Hyperplasia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo capsule, administered orally, twice daily for 24 weeks, followed by active treatment with crinecerfont for at least 1 year.

Drug: Crinecerfont; Drug: Placebo

Crinecerfont

EXPERIMENTAL

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

Interventions

Crinecerfont DRUG

CRF type 1 receptor antagonist

Also known as: NBI-74788, Crenessity

Crinecerfont; Placebo

Placebo DRUG

Non-active dosage form

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Have a diagnosis of any of the other known forms of classic CAH.
• Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy.
• Have a clinically significant unstable medical condition or chronic disease other than CAH.
• Have a history of cancer unless considered cured.
• Are pregnant.
• Have a known history of clinically significant arrhythmia or abnormalities on ECG.
• Have a known hypersensitivity to any corticotropin releasing hormone receptor antagonists.
• 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.
• Have current substance dependence, or current substance (drug) or alcohol abuse.
• Have had a blood loss ≥550 mL or donated blood or blood products within 8 weeks prior to the study.

Sponsors & Collaborators

• Neurocrine Biosciences: lead

Study Sites (70)

Neurocrine Clinical Site

Los Angeles, California, 90027, United States

Location

Neurocrine Clinical Site

San Diego, California, 92123, United States

Location

Neurocrine Clinical Site

San Francisco, California, 94143, United States

Location

Neurocrine Clinical Site

Aurora, Colorado, 80045, United States

Location

Neurocrine Clinical Site

Atlanta, Georgia, 30329, United States

Location

Neurocrine Clinical Site

Indianapolis, Indiana, 46202, United States

Location

Neurocrine Clinical Site

Bethesda, Maryland, 20982, United States

Location

Neurocrine Clinical Site

Boston, Massachusetts, 02115, United States

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Neurocrine Clinical Site

Ann Arbor, Michigan, 48109, United States

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Neurocrine Clinical Site

Minneapolis, Minnesota, 55454, United States

Location

Neurocrine Clinical Site

Rochester, Minnesota, 55905, United States

Location

Neurocrine Clinical Site

St Louis, Missouri, 63110, United States

Location

Neurocrine Clinical Site

Great Neck, New York, 11021, United States

Location

Neurocrine Clinical Site

New York, New York, 10029, United States

Location

Neurocrine Clinical Site

Winston-Salem, North Carolina, 27157, United States

Location

Neurocrine Clinical Site

Tulsa, Oklahoma, 74135, United States

Location

Neurocrine Clinical Site

Philadelphia, Pennsylvania, 19104, United States

Location

Neurocrine Clinical Site

Pittsburgh, Pennsylvania, 15224, United States

Location

Neurocrine Clinical Site

Dallas, Texas, 75390, United States

Location

Neurocrine Clinical Site

Seattle, Washington, 98105, United States

Location

Neurocrine Clinical Site

Graz, 8036, Austria

Location

Neurocrine Clinical Site

Vienna, 1090, Austria

Location

Neurocrine Clinical Site

Brussels, 1070, Belgium

Location

Neurocrine Clinical Site

Leuven, 3000, Belgium

Location

Neurocrine Clinical Site

Sofia, 1431, Bulgaria

Location

Neurocrine Clinical Site

Sofia, 1606, Bulgaria

Location

Neurocrine Clinical Site

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Neurocrine Clinical Site

Hradec Králové, 50005, Czechia

Location

Neurocrine Clinical Site

Angers, 49933, France

Location

Neurocrine Clinical Site

Grenoble, 38700, France

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Neurocrine Clinical Site

Le Kremlin-Bicêtre, 94270, France

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Neurocrine Clinical Site

Nantes, 44093, France

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Neurocrine Clinical Site

Paris, 75651, France

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Neurocrine Clinical Site

Paris, 75679, France

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Neurocrine Clinical Site

Dresden, 01307, Germany

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Neurocrine Clinical Site

Essen, 45147, Germany

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Neurocrine Clinical Site

Frankfurt, 60590, Germany

Location

Neurocrine Clinical Site

Leipzig, 04103, Germany

Location

Neurocrine Clinical Site

Munich, 80336, Germany

Location

Neurocrine Clinical Site

Athens, 106 76, Greece

Location

Neurocrine Clinical Site

Athens, 115 27, Greece

Location

Neurocrine Clinical Site

Athens, 11527, Greece

Location

Neurocrine Clinical Site

Thessaloniki, 54642, Greece

Location

Neurocrine Clinical Site

Afula, 1834111, Israel

Location

Neurocrine Clinical Site

Beersheba, 8410101, Israel

Location

Neurocrine Clinical Site

Petah Tikva, 4941480, Israel

Location

Neurocrine Clinical Site

Tel Aviv, 64239, Israel

Location

Neurocrine Clinical Site

Ancona, 60126, Italy

Location

Neurocrine Clinical Site

Bologna, 40138, Italy

Location

Neurocrine Clinical Site

Florence, 50139, Italy

Location

Neurocrine Clinical Site

Messina, 98125, Italy

Location

Neurocrine Clinical Site

Milan, 20132, Italy

Location

Neurocrine Clinical Site

Milan, 20149, Italy

Location

Neurocrine Clinical Site

Naples, 80131, Italy

Location

Neurocrine Clinical Site

Padua, 35128, Italy

Location

Neurocrine Clinical Site

Roma, 00161, Italy

Location

Neurocrine Clinical Site

Leiden, 2333, Netherlands

Location

Neurocrine Clinical Site

Krakow, 31-011, Poland

Location

Neurocrine Clinical Site

Poznan, 60-355, Poland

Location

Neurocrine Clinical Site

Warsaw, 01-809, Poland

Location

Neurocrine Clinical Site

Porto, 4200-319, Portugal

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Neurocrine Clinical Site

Belgrade, 11000, Serbia

Location

Neurocrine Clinical Site

Madrid, 28034, Spain

Location

Neurocrine Clinical Site

Seville, 41013, Spain

Location

Neurocrine Clinical Site

Gothenburg, 41345, Sweden

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Neurocrine Clinical Site

Stockholm, 17176, Sweden

Location

Neurocrine Clinical Site

Cardiff, CF14 4HH, United Kingdom

Location

Neurocrine Clinical Site

London, WC1B 5EH, United Kingdom

Location

Neurocrine Clinical Site

Manchester, M20 4BX, United Kingdom

Location

Neurocrine Clinical Site

Salford, M6 8HD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38828955 DERIVED

Related Links

• Study website - CAHtalyst Study

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital

Interventions

crinecerfont

Condition Hierarchy (Ancestors)

Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Neurocrine Medical Information Call Center
• Organization: Neurocrine Biosciences

medinfo@neurocrine.com

877-641-3461

Study Officials

• Clinical Development Lead

  Neurocrine Biosciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2020
• First Posted: July 29, 2020
• Study Start: December 16, 2020
• Primary Completion: July 19, 2023
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 5, 2025
• Results First Posted: February 5, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); CA (1); GR (4); CZ (1); NL (1); IL (4); ES (2); BU (2); DE (5); IT (9); PL (3); FR (6); AU (2); BE (2); US (20); PT (1); GB (4)