A Ph2b to Evaluate Tildacerfont in the Reduction of Glucocorticoid Steroid Doses in Adult CAH

NCT04544410 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: SPR001-204CAHmelia 204
• Study Type: interventional
• Target: 100
• Locations: 15 countries
• Sites: 41

Brief Summary

An investigation of the ability of Tildacerfont to reduce supraphysiologic glucocorticoid dosing in classic Congenital adrenal hyperplasia (CAH) subjects up to 76 weeks of treatment. Optional open label extension up to 240 weeks.

Conditions

Congenital Adrenal Hyperplasia

Keywords

CAH; Adrenal Disorder; Congenital Adrenal Hyperplasia

Outcome Measures

Primary Outcomes (1)

• Change in Total Daily GC Dose in Subjects With Classic CAH Over the 24-week, Double Blind, Placebo-Controlled Treatment Period

  Absolute change from baseline (Day 1) in GC dose in HCe at Week 24. The analysis of absolute change in total daily GC dose in HCe will include data from Weeks 3, 6, 12, 18 and 24 in a mixed model

  24 Weeks

Secondary Outcomes (3)

• Effect of Tildacrfont in Reducing GC Use to Near-physiologic Levels While Maintaining Androgen Control in Subjects With CAH

  24 weeks

• Effect of Tildacrfont in Reducing GC Use to Near-physiologic Levels While Maintaining Androgen Control in Subjects With CAH

  24 Weeks

• Effectiveness in Reducing Cardiovascular Risk in Subjects With CAH

  24 Weeks

Study Arms (2)

Tildacerfont Group

EXPERIMENTAL

Tildacerfont administered daily via oral tablet for 24 weeks at dose level 1; followed by open label tildacerfont for 52 weeks

Drug: Tildacerfont/Placebo

Placebo

PLACEBO COMPARATOR

Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont for 52 weeks

Drug: Tildacerfont/Placebo

Interventions

Tildacerfont/Placebo DRUG

Tablet, administered daily

Also known as: SPR001

Placebo; Tildacerfont Group

Eligibility Criteria

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

You may qualify if:

• Male and female subjects ≥18 years old at screening
• Has a known childhood diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented (at any time) elevated 17-hydroxyprogesterone (17-OHP) and currently treated with hydrocortisone (HC), HC acetate, prednisone, prednisolone, methylprednisolone, dexamethasone (or a combination of the aforementioned glucocorticoid \[GCs\])
• Has lower limit of detection ≤ androstenedione (A4) ≤ 2.5x upper limit of normal (ULN) at screening measured before a morning GC dose
• Has been on a stable, supraphysiologic dose of GC replacement (defined as ≥30 mg/day and ≤60 mg/day in HCe) for ≥1 month before screening
• For subjects with the salt-wasting form of CAH, subject has been on a stable dose of mineralocorticoid replacement for ≥1 month before screening
• Agrees to follow contraception guidelines. Male subjects must also agree to refrain from donating sperm throughout the Treatment Period and for 90 days after the last dose of study drug
• Is able to understand all study procedures and risks involved and provides written informed consent indicating willingness to comply with all aspects of the protocol

You may not qualify if:

• Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21-hydroxylase deficiency)
• Has a history that includes bilateral adrenalectomy or hypopituitarism
• Has a history of allergy or hypersensitivity to tildacerfont, any of its excipients, or any other CRF1 receptor antagonist
• Shows clinical signs or symptoms of adrenal insufficiency
• Has had a clinically significant unstable medical condition, medically significant illness, or chronic disease occurring within 30 days of screening, including but not limited to:
• An ongoing malignancy or \<3 years of remission history from any malignancy, other than successfully treated localized skin cancer
• eGFR of \<45 mL/min/1.73 m2
• Current or history of liver disease (with the exception of Gilbert's syndrome)
• History of alcohol or substance abuse within the last year, or any significant history of alcohol or substance abuse that would likely prevent the subject from reliably participating in the study, based on the opinion of the Investigator
• Active hepatitis B, hepatitis C, or HIV at screening
• Subjects who plan to undergo bariatric surgery during the study are excluded
• Any other condition that would impact subject safety or confound interpretation of study results
• Increased risk of suicide based on the Investigator's judgment or the results of the C-SSRS conducted at screening and baseline (eg, C-SSRS Type 3, 4, or 5 ideation within the past 6 months or any suicidal behavior within the past 12 months) b. Hospital Anxiety and Depression Scale (HADS) score \>12 for either depression or anxiety at screening or baseline
• Has clinically significant abnormal ECG or clinical laboratory results. Abnormal results that must be reviewed and discussed with the Medical Monitor to determine eligibility for this study include but are not limited to:
• Any clinically meaningful abnormal ECG results, including QTcF \>450 ms for male participants or \>470 ms for female participants

Sponsors & Collaborators

• Spruce Biosciences: lead

Study Sites (43)

Spruce Study Site

Birmingham, Alabama, 35294, United States

Location

Spruce Study Site

Los Angeles, California, 90027, United States

Location

Spruce Study Site

San Diego, California, 92123, United States

Location

Spruce Study Site

Indianapolis, Indiana, 46202, United States

Location

Spruce Study Site

Baltimore, Maryland, 21287, United States

Location

Spruce Biosciences Clinical Site

Ann Arbor, Michigan, 48109, United States

Location

Spruce Study Site

Minneapolis, Minnesota, 55454, United States

Location

Spruce Study Site

New Brunswick, New Jersey, 08901, United States

Location

Spruce Study Site

Canton, Ohio, 44718, United States

Location

Spruce Study Site

Cincinnati, Ohio, 45219, United States

Location

Spruce Study Site

Cleveland, Ohio, 44195, United States

Location

Spruce Study Site

Columbus, Ohio, 43210, United States

Location

Spruce Study Site

Philadelphia, Pennsylvania, 19104, United States

Location

Spruce Study Site

Philadelphia, Pennsylvania, 19107, United States

Location

Spruce Study Site

Philadelphia, Pennsylvania, 19140, United States

Location

Spruce Study Site

Providence, Rhode Island, 02903, United States

Location

Spruce Study Site

Columbia, South Carolina, 29203, United States

Location

Spruce Study Site

Fort Worth, Texas, 76104, United States

Location

Spruce Study Site

Blacktown, Australia

Location

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Brisbane, 4029, Australia

Location

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Elizabeth Vale, Australia

Location

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Parkville, Australia

Location

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Curitiba, Brazil

Location

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São Paulo, Brazil

Location

Spruce Study Site

Ottawa, Ontario, Canada

Location

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Sherbrooke, Quebec, J1H 5N4, Canada

Location

Spruce Study Site

Tallinn, Estonia

Location

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Tartu, Estonia

Location

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Munich, Germany

Location

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Roma, Italy

Location

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Riga, Latvia

Location

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Kaunas, Lithuania

Location

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Krakow, Poland

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Warsaw, Poland

Location

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Bucharest, Romania

Location

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Seoul, South Korea

Location

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Barcelona, Spain

Location

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Madrid, Spain

Location

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Seville, Spain

Location

Spruce Study Site

Tarragona, Spain

Location

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Stockholm, Sweden

Location

Spruce Study Site

Istanbul, Turkey (Türkiye)

Location

Spruce Study Site

Birmingham, B15 2GW, United Kingdom

Location

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital; Adrenal Gland Diseases

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; Endocrine System Diseases; Gonadal Disorders

Limitations and Caveats

Due to early termination of the study, not all assessments were performed. Additionally, due to protocol deviations, some assessments and samples were not collected therefore data are not available for every assessment from every participant.

Results Point of Contact

• Title: Spruce Clinical Trials
• Organization: Spruce Biosciences

clinicaltrials@sprucebio.com

415-655-4169

Study Officials

• Ron Newfield, M.D

  Rady Children's Hospital-San Diego and Professor of clinical pediatrics at UC San Diego School of Medicine.

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind for first 24 weeks, then open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized in a 1:1 manner to either Tildacerfont or Placebo for 24 weeks followed by 52 weeks open label Tildacerfont

Study Record Dates

• First Submitted: August 30, 2020
• First Posted: September 10, 2020
• Study Start: February 22, 2021
• Primary Completion: October 31, 2024
• Study Completion: January 31, 2025
• Last Updated: October 1, 2025
• Results First Posted: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); ES (4); KR (1); TU (1); US (18); BR (2); LA (1); LI (1); RO (1); AU (4); CA (2); SE (1); DE (1); IT (1); PL (2)