This is a randomized, double-blinded, Placebo controlled trial with a 3-part treatment period that will evaluate the efficacy and safety of up to 70 weeks of treatment with tildacerfont in subjects with classic Congenital adrenal hyperplasia (CAH) who have elevated blood hormones at baseline

Phase 1

• Conditions: Classic Congenital Adrenal Hyperplasia; MedDRA version: 20.0Level: LLTClassification code 10010323Term: Congenital adrenal hyperplasiaSystem Organ Class: 100000004850; Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

• Registration Number: EUCTR2019-004764-22-PL
• Lead Sponsor: Spruce Biosciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-24
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 72

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.For subjects with the salt-wasting form of CAH, the subject is on a stable dose of mineralocorticoid replacement for =1 month before screening
4.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.
5. 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 67
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 5

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, or any of its excipients or any other CRF1 receptor antagonist
4.Current treatment with dexamethasone as GC therapy for CAH
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:
a. An ongoing malignancy or <3 years of remission history from any malignancy, other than successfully treated localized skin cancer
b. Estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m2
c.Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at screening
8.Had or has a clinically significant psychiatric disorder, including the following:
a.Psychiatric conditions, including but not limited to depression, bipolar disorder, schizophrenia or schizoaffective disorder that are not effectively controlled on medication and may have an adverse impact on study compliance. Symptoms including hallucinations, delusions and psychosis are exlcusionary.
b.Increased risk of suicide based on the Investigator’s judgment or the results of the Columbia–Suicide Severity Rating Scale (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)
c.HADS score >12 for either depression or anxiety at screening or Week 6
9. Has clinically significant abnormal ECG or clinical laboratory results.
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
a.rosiglitazone, aromatase inhibitors, testosterone, or growth hormones or any other medication or supplement that could impact subject safety or confound interpretation of study results
b.drugs listed in section 13.1
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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effect of tildacerfont in reducing A4 in subjects with CAH over 12 weeks;Secondary Objective: •To evaluate the effect of tildacerfont on A4 levels in subjects with CAH over 12 weeks<br>•To evaluate the effect of tildacerfont on 17-OHP levels in subjects with CAH over 12 weeks<br>•To evaluate the effect of tildacerfonr in reducing TART(s) in male CAH subjects with TART(s) at baseline after 12 weeks on treatment;Primary end point(s): Percent change from baseline in A4 after 12 weeks on treatment (Week 18);Timepoint(s) of evaluation of this end point: Subjects blood will be collected at Baseline and Week 18.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Proportion of subjects who achieve:<br>• A4 = ULN after 12 weeks on treatment (Week 18)<br>•17-OHP = 1200 ng/dL after 12 weeks on treatment (Week 18);Timepoint(s) of evaluation of this end point: Subjects blood will be collected at Baseline and Week 18.