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

Phase 2

Terminated

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

• Registration Number: NCT04457336
• Lead Sponsor: Spruce Biosciences

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.

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 Timeline

• Study First Submitted: 2020-06-25
• Study First Submitted QC: 2020-06-30
• Study First Posted: 2020-07-07
• Study Start: 2020-08-26
• Primary Completion: 2024-02-09
• Study Completion: 2024-05-23
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-06
• Last Update Posted: 2024-06-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

• Male and female subjects over 18 years old, inclusive
• Has a known childhood diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented 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 ≥15 mg/day and ≤60 mg/day in HC equivalents
• 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
• Current treatment with dexamethasone as GC therapy for CAH. 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.
• Shows clinical signs or symptoms of adrenal insufficiency

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tildacerfont Group 2	Tildacerfont/Placebo	Tildacerfont administered daily via oral tablet for 12 weeks at dose level 2
Tildacerfont Group 3	Tildacerfont/Placebo	Tildacerfont administered daily via oral tablet for 70 weeks at dose level 3
Placebo	Tildacerfont/Placebo	Placebo administered daily via oral tablet for 12 weeks.
Tildacerfont Group 1	Tildacerfont/Placebo	Tildacerfont administered daily via oral tablet for 12 weeks at dose level 1

Primary Outcome Measures

Name	Time	Method
Change in androstenedione	12 weeks	Percent change of androstenedione

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects who achieve reduction A4 levels	12 weeks	Proportion of subjects who achieve A4 ≤ ULN
Proportion of subjects who achieve reduction in 17-OHP	12 weeks	Proportion of subjects who achieve 17-OHP≤ 1200ng/dL
Effectiveness in reducing TART(s) in Male CAH subjects	12 weeks	Change in lesion volume of TART(s) from baseline

Trial Locations

Locations (3)

Spruce Study Site; 🇬🇧 Birmingham, United Kingdom

Spruce Clinical Site; 🇺🇸 Fort Worth, Texas, United States

Spruce study site; 🇦🇺 Brisbane, Australia