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

Phase 2

Terminated

• Conditions: Congenital Adrenal Hyperplasia
• Interventions: Drug: Tildacerfont/Placebo

• Registration Number: NCT04544410
• Lead Sponsor: Spruce Biosciences

Brief Summary

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

Detailed Description

This is a study that will evaluate the ability of Tildacerfont to reduce the glucocorticoid steroid dose used by adult CAH subjects. The first 24-weeks will be a double-blind, placebo controlled, comparison of Tildacerfont vs Placebo. The following 52-weeks will allow all subjects to move to open label Tildacerfont to continue to reduce steroid dose where appropriate, and observe long term safety. Subjects will be offered a long term open label extension up to 240 weeks.

Study Timeline

• Study First Submitted: 2020-08-30
• Study First Submitted QC: 2020-09-03
• Study First Posted: 2020-09-10
• Study Start: 2020-09-29
• Primary Completion: 2024-06-25
• Status Verified: 2025-01
• Study Completion: 2025-01-31
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Male and female subjects over 18 years old, inclusive
• Has a documented historical diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented elevated 17-OHP and currently treatment with HC, HC acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned GCs)
• Has been on a stable, supraphysiologic dose of GC replacement 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Proportion of subjects who can reduce GC dose at Week 24	24 Weeks	Absolute change from baseline in GC dose in HCe (mg/day and mg/m2/day) at Week 24

Secondary Outcome Measures

Name	Time	Method
Change in the median cumulative HCe dose in subjects with CAH	24 Weeks	Proportion of subjects with baseline GC dose ≤ 35mg HCe who achieve GC dose ≤11 mg/m2/day in HCe and A4 ≤ 1.2x baseline or ≤ ULN at Week 24
Percentage change in GC use in subjects with CAH	24 weeks	Proportion of subjects with GC dose ≤11mg/m2/day in HCe and A4 ≤1.2x baseline or A4 ≤ ULN at Week 24
Effectiveness in reducing cardiovascular risk in subjects with CAH	24 Weeks	Proportion of subjects with improvement in at least one cardiovascular risk factor at week 24

Trial Locations

Locations (2)

Spruce Study Site; 🇬🇧 Birmingham, United Kingdom

Spruce Biosciences Clinical Site; 🇺🇸 Ann Arbor, Michigan, United States