A Ph2b to Evaluate Clinical Efficacy and Safety of Tildacerfont in Adult CAH

NCT04457336 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: SPR001-203CAHmelia 203
• Study Type: interventional
• Target: 96
• Locations: 19 countries
• Sites: 61

Brief Summary

An investigation of the efficacy and safety of up to 70 weeks of treatment with Tildacerfont in subjects with classic CAH who have elevated biomarkers at baseline on their current GC regimen. Optional open label treatment extension period up to 240 weeks with 200mg Tildacerfont QD.

Conditions

Congenital Adrenal Hyperplasia

Keywords

CAH; Adrenal Disorder; Congenital Adrenal Hyperplasia

Outcome Measures

Primary Outcomes (1)

• To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Over 12 Weeks

  Assessment of dose response for change from baseline in log A4 after 12 weeks on double-blind placebo-controlled treatment (Week 18)

  Baseline and 12 weeks of treatment (Week 18)

Secondary Outcomes (4)

• To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks

  12 weeks

• To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks

  12 weeks

• To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks

  12 weeks

• To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks

  12 weeks

Study Arms (4)

Tildacerfont Group 1

EXPERIMENTAL

Tildacerfont administered daily via oral tablet for 12 weeks at dose level 1

Drug: Tildacerfont/Placebo

Tildacerfont Group 2

EXPERIMENTAL

Tildacerfont administered daily via oral tablet for 12 weeks at dose level 2

Drug: Tildacerfont/Placebo

Tildacerfont Group 3

EXPERIMENTAL

Tildacerfont administered daily via oral tablet for 70 weeks at dose level 3

Drug: Tildacerfont/Placebo

Placebo

PLACEBO COMPARATOR

Placebo administered daily via oral tablet for 12 weeks.

Drug: Tildacerfont/Placebo

Interventions

Tildacerfont/Placebo DRUG

Tablet, administered daily

Also known as: SPR001

Placebo; Tildacerfont Group 1; Tildacerfont Group 2; Tildacerfont Group 3

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-OHP and currently treated with HC, HC acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned GCs)
• Has been on a stable, supraphysiologic dose of GC replacement (defined as ≥15 mg/day and ≤60 mg/day in HCe) for ≥1 month before screening
• Has A4 \>ULN at both screening and Week 4 (measured before any AM GC dose) if daily GC dose \<30 mg OR has A4 \>2.5x ULN at both screening and Week 4 (measured before any AM GC dose)
• 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
• Current treatment with dexamethasone as GC therapy for CAH
• a. Prior treatment with dexamethasone is allowed as long as the transition to an alternative GC regimen (eg, HC, prednisone, or prednisolone) has resulted in a stable dose of GC replacement for ≥1 month before screening.
• Is not adherent to GC or study drug dosing regimen during the Run-in Period (defined as taking \<80% of expected doses based on drug accountability)
• 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

Sponsors & Collaborators

• Spruce Biosciences: lead

Study Sites (65)

Spruce Study Site

Birmingham, Alabama, 35294, United States

Location

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Los Angeles, California, 90027, United States

Location

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Orange, California, 92868, United States

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Sacramento, California, 95817, United States

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Englewood, Colorado, 80113, United States

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Tampa, Florida, 33612, United States

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West Palm Beach, Florida, 33401, United States

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Chicago, Illinois, 60611, United States

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Indianapolis, Indiana, 46202, United States

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Baltimore, Maryland, 21287, United States

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Minneapolis, Minnesota, 55454, United States

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Rochester, Minnesota, 55905, United States

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Las Vegas, Nevada, 89148, United States

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Hickory, North Carolina, 28601, United States

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Canton, Ohio, 44718, United States

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Cincinnati, Ohio, 45219, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, 43210, United States

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Bend, Oregon, 97702, United States

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Philadelphia, Pennsylvania, 19104, United States

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Philadelphia, Pennsylvania, 19107, United States

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Providence, Rhode Island, 02903, United States

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Columbia, South Carolina, 28203, United States

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Memphis, Tennessee, 38163, United States

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Austin, Texas, 78731, United States

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Dallas, Texas, 75093, United States

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Edinburg, Texas, 78539, United States

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Fort Worth, Texas, 76104, United States

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Nedlands, Western Australia, 6009, Australia

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Brisbane, Australia

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Elizabeth Vale, Australia

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Melbourne, Australia

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Brasília, Brazil

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São Paulo, Brazil

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St. John's, Newfoundland and Labrador, Canada

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London, Ontario, Canada

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Ottawa, K1H7W9, Canada

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Sherbrooke, J1H 5N4, Canada

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Aarhus, Denmark

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Copenhagen, Denmark

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Tallinn, Estonia

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Tartu, Estonia

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Munich, Germany

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Dublin, Ireland

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Milan, Italy

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Napoli, Italy

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Rome, Italy

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Torino, Italy

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Riga, Latvia

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Kaunas, Lithuania

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Nijmegen, Netherlands

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Krakow, Poland

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Warsaw, Poland

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Bucharest, Romania

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Seoul, South Korea

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Barcelona, Spain

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Madrid, Spain

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Seville, Spain

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Tarragona, Spain

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Falun, Sweden

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Stockholm, Sweden

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Sankt Gallen, Switzerland

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Zurich, Switzerland

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Istanbul, Turkey (Türkiye)

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Birmingham, 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

Results Point of Contact

• Title: Dina Ayala-Jones, Associate Director, Clinical Development Operations
• Organization: Spruce Biosciences

djones@sprucebio.com

424.558.1211

Study Officials

• Kyriakie Sarafoglou, M.D

  Dept. of Pediatrics, Divisions of Endocrinology and Genetics & Metabolism, Univ. of Minnesota

  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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized in a 1:1:1:1 manner to one of three doses of Tildacerfont or Placebo.

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: July 7, 2020
• Study Start: August 26, 2020
• Primary Completion: February 9, 2024
• Study Completion: May 23, 2024
• Last Updated: July 8, 2025
• Results First Posted: July 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); LA (1); AU (4); ES (2); CA (4); DK (2); CH (2); RO (1); DE (1); US (28); NL (1); LI (1); SE (2); PL (2); BR (2); IT (4); KR (1); TU (1); IE (1)