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

Sponsor

Spruce Biosciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04544410

Collaborator

(none)

Enrollment

Locations

Arms

59.1

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Congenital Adrenal Hyperplasia	Drug: Tildacerfont/Placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects will be randomized in a 1:1 manner to either Tildacerfont or Placebo for 24 weeks followed by 52 weeks open label TildacerfontSubjects will be randomized in a 1:1 manner to either Tildacerfont or Placebo for 24 weeks followed by 52 weeks open label Tildacerfont

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Double-Blind for first 24 weeks, then open label

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 29, 2020

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tildacerfont Group Tildacerfont administered daily via oral tablet for 24 weeks at dose level 1; followed by open label tildacerfont for 52 weeks	Drug: Tildacerfont/Placebo Tablet, administered daily Other Names: SPR001
Placebo Comparator: Placebo Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont for 52 weeks	Drug: Tildacerfont/Placebo Tablet, administered daily Other Names: SPR001

Arm

Intervention/Treatment

Experimental: Tildacerfont Group

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

Drug: Tildacerfont/Placebo

Tablet, administered daily

Other Names:

SPR001

Placebo Comparator: Placebo

Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont for 52 weeks

Drug: Tildacerfont/Placebo

Tablet, administered daily

Other Names:

SPR001

Outcome Measures

Primary Outcome Measures

Proportion of subjects who can reduce GC dose at Week 24 [24 Weeks]
Proportion of subjects with at least a 5 mg/day HCe reduction from baseline in GC dose and A4 ≤ULN at Week 24

Secondary Outcome Measures

Percentage change in GC use in subjects with CAH [24 weeks]
Percent change from baseline in GC dose at week 24
Change in the median cumulative HCe dose in subjects with CAH [24 Weeks]
Median total cumulative GC dose in HCe 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
Effectiveness in improving HOMA-IR in subjects with CAH [24 Weeks]
Change from baseline in the HOMA-IR at Week 24
Effect on body weight in subjects with CAH [24 weeks]
Percent change from baseline in body weight after 24 weeks of tildacerfont treatment
Effect on body weight in subjects with CAH [52 weeks]
Percent change from baseline in body weight after 52 weeks of tildacerfont treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Spruce Study Site	Birmingham	Alabama	United States	35294
2	Spruce Study Site	Los Angeles	California	United States	90027
3	Spruce Clinical Site	Orange	California	United States	92868
4	Spruce Study Site	Sacramento	California	United States	95821
5	Spruce Study Site	San Diego	California	United States	92123
6	Spruce Study Site	Tampa	Florida	United States	33612
7	Spruce Study Site	Indianapolis	Indiana	United States	46202
8	Spruce Study Site	Kansas City	Kansas	United States	66160
9	Spruce Study Site	Jefferson	Louisiana	United States	70121
10	Spruce Study Site	Baltimore	Maryland	United States	21287
11	Spruce Study Site	Camp Springs	Maryland	United States	20746
12	Spruce Study Site	Boston	Massachusetts	United States	02111
13	Spruce Biosciences Clinical Site	Ann Arbor	Michigan	United States	48109
14	Spruce Study Site	Minneapolis	Minnesota	United States	55454
15	Spruce Study Site	Rochester	Minnesota	United States	55905
16	Spruce Study Site	Las Vegas	Nevada	United States	89148
17	Spruce Study Site	Reno	Nevada	United States	89557
18	Spruce Study Site	New Brunswick	New Jersey	United States	08901
19	Spruce Study Site	Bronx	New York	United States	10467
20	Spruce Study Site	Syracuse	New York	United States	13057
21	Spruce Study Site	Hickory	North Carolina	United States	28601
22	Spruce Study Site	Canton	Ohio	United States	44718
23	Spruce Study Site	Cincinnati	Ohio	United States	45219
24	Spruce Study Site	Cleveland	Ohio	United States	44195
25	Spruce Study Site	Columbus	Ohio	United States	43210
26	Spruce Study Site	Edmond	Oklahoma	United States	73034
27	Spruce Study Site	Bend	Oregon	United States	99702
28	Spruce Study Site	Philadelphia	Pennsylvania	United States	19104
29	Spruce Study Site	Philadelphia	Pennsylvania	United States	19107
30	Spruce Study Site	Philadelphia	Pennsylvania	United States	19140
31	Spruce Study Site	Columbia	South Carolina	United States	29203
32	Spruce Study Site	Memphis	Tennessee	United States	38163
33	Spruce Study Site	Dallas	Texas	United States	75231
34	Spruce Study Site	Edinburg	Texas	United States	78539
35	Spruce Study Site	Fort Worth	Texas	United States	76104
36	Spruce Study Site	Richmond	Virginia	United States	23298
37	Spruce Study Site	Seattle	Washington	United States	98105
38	Spruce Study Site	Nedlands	Western Australia	Australia	6009
39	Spruce Study Site	Camperdown		Australia
40	Spruce Study Site	Melbourne		Australia
41	Spruce Study Site	Sydney		Australia
42	Spruce Study Site	Saint Johns	Newfoundland and Labrador	Canada
43	Spruce Study Site	London	Ontario	Canada
44	Spruce Study Site	Sherbrooke		Canada	J1H 5N4
45	Spruce Study Site	Aarhus		Denmark
46	Spruce Study Site	Copenhagen		Denmark
47	Spruce Study Site	Munich		Germany
48	Spruce Study Site	Nijmegen		Netherlands
49	Spruce Study Site	Kraków		Poland
50	Spruce Study Site	Barcelona		Spain
51	Spruce Study Site	Madrid		Spain
52	Spruce Study Site	Sevilla		Spain
53	Spruce Study Site	Falun		Sweden
54	Spruce Study Site	Liverpool		United Kingdom
55	Spruce Study Site	London		United Kingdom

Sponsors and Collaborators

Spruce Biosciences

Investigators

Principal Investigator: Ron Newfield, M.D, Rady Children's Hospital-San Diego and Professor of clinical pediatrics at UC San Diego School of Medicine.