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

A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Adult Subjects With Classic Congenital Adrenal Hyperplasia

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.

Study Overview

• Status: Terminated
• Conditions: Congenital Adrenal Hyperplasia
• Intervention / Treatment: Drug: Tildacerfont/Placebo

Detailed Description

This is a study that will test the efficacy and safety of Tildacerfont. The first 12-weeks will be a double-blind, placebo controlled, dose ranging study. The following 58-weeks will assess the long term safety of Tildacerfont. Optional open label treatment extension period up to 240 weeks with 200mg Tildacerfont QD.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • Spruce Study Site
  • Elizabeth Vale, Australia
    • Spruce Study Site
  • Melbourne, Australia
    • Spruce Study Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Spruce Study Site
• Brazil
  • Brasília, Brazil
    • Spruce Study Site
  • São Paulo, Brazil
    • Spruce Study Site
• Canada
  • Ottawa, Canada, K1H7W9
    • Spruce Study Site
  • Sherbrooke, Canada, J1H 5N4
    • Spruce Study Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada
      • Spruce Study Site
  • Ontario
    • London, Ontario, Canada
      • Spruce Study Site
• Denmark
  • Aarhus, Denmark
    • Spruce Study Site
  • Copenhagen, Denmark
    • Spruce Study Site
• Estonia
  • Tallinn, Estonia
    • Spruce Study Site
  • Tartu, Estonia
    • Spruce Study Site
• Germany
  • Munich, Germany
    • Spruce Study Site
• Ireland
  • Dublin, Ireland
    • Spruce Study Site
• Italy
  • Milan, Italy
    • Spruce Study Site
  • Napoli, Italy
    • Spruce Study Site
  • Rome, Italy
    • Spruce Study Site
  • Torino, Italy
    • Spruce Study Site
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Spruce Study Site
• Latvia
  • Riga, Latvia
    • Spruce Study Site
• Lithuania
  • Kaunas, Lithuania
    • Spruce Study Site
• Netherlands
  • Nijmegen, Netherlands
    • Spruce Study Site
• Poland
  • Kraków, Poland
    • Spruce Study Site
  • Warsaw, Poland
    • Spruce Study Site
• Romania
  • Bucharest, Romania
    • Spruce Study Site
• Spain
  • Barcelona, Spain
    • Spruce Study Site
  • Madrid, Spain
    • Spruce Study Site
  • Sevilla, Spain
    • Spruce Study Site
  • Tarragona, Spain
    • Spruce Study Site
• Sweden
  • Falun, Sweden
    • Spruce Study Site
  • Stockholm, Sweden
    • Spruce Study Site
• Switzerland
  • Saint Gallen, Switzerland
    • Spruce Study Site
  • Zürich, Switzerland
    • Spruce Study Site
• Turkey
  • Istanbul, Turkey
    • Spruce Study Site
• United Kingdom
  • Birmingham, United Kingdom
    • Spruce Study Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Spruce Study Site
  • California
    • Los Angeles, California, United States, 90027
      • Spruce Study Site
    • Orange, California, United States, 92868
      • Spruce Clinical Site
    • Sacramento, California, United States, 95817
      • Spruce Study Site
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Spruce Study Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Spruce Clinical Site
    • West Palm Beach, Florida, United States, 33401
      • Spruce Study Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Spruce Study Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Spruce Clinical Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Spruce Study Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • Spruce Clinical Site
    • Rochester, Minnesota, United States, 55905
      • Spruce Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Spruce Clinical Site
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • Spruce Study Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Spruce Study Site
    • Cincinnati, Ohio, United States, 45219
      • Spruce Study Site
    • Cleveland, Ohio, United States, 44195
      • Spruce Study Site
    • Columbus, Ohio, United States, 43210
      • Spruce Study Site
  • Oregon
    • Bend, Oregon, United States, 97702
      • Spruce Clinical Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Spruce Study Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Spruce Study Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Spruce Study Site
  • South Carolina
    • Columbia, South Carolina, United States, 28203
      • Spruce Study Site
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • Spruce Clinical Site
  • Texas
    • Austin, Texas, United States, 78731
      • Spruce Study Site
    • Dallas, Texas, United States, 75093
      • Spruce Study Site
    • Edinburg, Texas, United States, 78539
      • Spruce Clinical Site
    • Fort Worth, Texas, United States, 76104
      • Spruce 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. Male and female subjects ≥18 years old at screening
2. 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)
3. 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
4. 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)
5. For subjects with the salt-wasting form of CAH, subject has been on a stable dose of mineralocorticoid replacement for ≥1 month before screening
6. 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.
7. 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.

Exclusion Criteria:

1. Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21 hydroxylase deficiency)
2. Has a history that includes bilateral adrenalectomy or hypopituitarism
3. Has a history of allergy or hypersensitivity to tildacerfont, any of its excipients, or any other CRF1 receptor antagonist

4. 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.

5. 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)
6. Shows clinical signs or symptoms of adrenal insufficiency

7. 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:

   1. An ongoing malignancy or <3 years of remission history from any malignancy, other than successfully treated localized skin cancer
   2. eGFR of <45 mL/min/1.73 m2
   3. Current or history of liver disease (with the exception of Gilbert's syndrome).
   4. 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
   5. Active hepatitis B, hepatitis C, or HIV at screening
   6. Subjects who plan to undergo bariatric surgery during the study are excluded.
   7. Any other condition that would impact subject safety or confound interpretation of study results

8. Psychiatric conditions, including but not limited to bipolar disorder, schizophrenia, or schizoaffective disorders that are not effectively controlled on medication and may have an adverse impact on study compliance. Symptoms including hallucinations, delusions, and psychosis are exclusionary. Additionally:

   1. Increased risk of suicide based on the Investigator's judgment or the results of the C-SSRS conducted at screening and Week 6 (eg, C-SSRS Type 3, 4, or 5 ideation within the past 6 months or any suicidal behavior within the past 12 months)
   2. HADS score >12 for either depression or anxiety at screening or Week 6

9. 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:

   1. Any clinically meaningful abnormal ECG results, including QTcF >450 ms for male participants or >470 ms for female participants
   2. ALT >2x ULN
   3. Total bilirubin >1.5x ULN
   4. Total bile acids >5x ULN
10. Routinely works overnight shifts
11. Subjects with travel plans/work schedules that result in significant and frequent changes in time zones (>2 hours) will require Medical Monitor approval for enrollment.
12. Females who are pregnant or nursing
13. Use of any other investigational drug from 30 days or 5 half-lives (whichever is longer) before screening to the end of the study

14. Use of the following drugs from 30 days or 5 half-lives (whichever is longer) before Day 1 to the end of the study:

    1. Rosiglitazone, aromatase inhibitors, testosterone, growth hormones, or any other medication or supplement that could impact subject safety or confound interpretation of study results
    2. The following drugs:

    i. Moderate to strong inhibitors and/or inducers of CYP3A4 ii. Sensitive substrates or narrow-therapeutic-range substrates of CYP3A4 (except hormonal contraception containing ≤35 μg ethinyl estradiol) iii. Sensitive substrates or narrow-therapeutic-range substrates of BCRP (except those that can be administered QD in the morning, separated by approximately 10 hours from evening administration of study drug)

15. Donation or receipt of blood from 90 days before Screening to the end of the study; donation or receipt of platelets, white blood cells, or plasma from 30 days before Screening to the end of 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tildacerfont Group 1; Tildacerfont administered daily via oral tablet for 12 weeks at dose level 1	Drug: Tildacerfont/Placebo; Tablet, administered daily; Other Names: SPR001
Experimental: Tildacerfont Group 2; Tildacerfont administered daily via oral tablet for 12 weeks at dose level 2	Drug: Tildacerfont/Placebo; Tablet, administered daily; Other Names: SPR001
Experimental: Tildacerfont Group 3; Tildacerfont administered daily via oral tablet for 70 weeks at dose level 3	Drug: Tildacerfont/Placebo; Tablet, administered daily; Other Names: SPR001
Placebo Comparator: Placebo; Placebo administered daily via oral tablet for 12 weeks.	Drug: Tildacerfont/Placebo; Tablet, administered daily; Other Names: SPR001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks	Absolute change from baseline in A4 as determined via application of the delta theorem to the log scale analysis results after 12 weeks on double-blind, placebo-controlled treatment (Week 18). Results show mean Treatment Effect of Dose vs Placebo. A negative value represents a reduction in absolute concentration compared to baseline.	12 weeks
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks	Change from baseline in A4 as assessed on the log scale after 12 weeks on double-blind, placebo-controlled treatment (Week 18). Results show mean % of Treatment Effect of Dose vs Placebo. A negative value represents a % reduction from baseline.	12 weeks
To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks	Change from baseline in 17-OHP as assessed on the log scale after 12 weeks on double-blind, placebo-controlled treatment (Week 18). A negative value represents a % reduction from baseline.	12 weeks
To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks	Absolute change from baseline in 17-OHP as determined via application of the delta theorem to the log scale analysis results after 12 weeks on double-blind, placebo-controlled treatment (Week 18). Results show mean Treatment Effect of Dose vs Placebo. A negative value represents a reduction in absolute concentration compared to baseline.	12 weeks

Collaborators and Investigators

• Sponsor: Spruce Biosciences
• Investigators: Principal Investigator: Kyriakie Sarafoglou, M.D, Dept. of Pediatrics, Divisions of Endocrinology and Genetics & Metabolism, Univ. of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2020
• Primary Completion (Actual): February 9, 2024
• Study Completion (Actual): May 23, 2024

Study Registration Dates

• First Submitted: June 25, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Congenital Adrenal Hyperplasia; CAH; Adrenal Disorder
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; 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; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction
• Other Study ID Numbers: SPR001-203; CAHmelia 203 (Other Identifier: Spruce Biosciences)

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