Trial Outcomes & Findings for A Ph2b to Evaluate Tildacerfont in the Reduction of Glucocorticoid Steroid Doses in Adult CAH (NCT NCT04544410)

Last Updated: 2025-10-01

Results Overview

Absolute change from baseline (Day 1) in GC dose in HCe at Week 24. The analysis of absolute change in total daily GC dose in HCe will include data from Weeks 3, 6, 12, 18 and 24 in a mixed model

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

100 participants

Primary outcome timeframe

24 Weeks

Results posted on

2025-10-01

Participant Flow

This study randomized approximately 100 participants with classic congenital adrenal hyperplasia (CAH) currently receiving glucocorticoid (GC) at a supraphysiologic dose

An optional Screening visit to capture information within 45 days of Day 1 in this study may have been used to determine eligibility and fulfill screening requirements for this study. A 6- or 12 week GC Conversion Period (Week -12 to either Week -6 or Week -2 \[±3 days\]) for participants on dexamethasone at the initial Screening Visit who agreed to convert to a non-dexamethasone regimen as determined by their physician.

Participant milestones

Participant milestones
Measure	Tildacerfont Group Tildacerfont 200 mg administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks	Placebo Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks
Double-blind Treatment Period STARTED	48	52
Double-blind Treatment Period COMPLETED	44	50
Double-blind Treatment Period NOT COMPLETED	4	2
Open-Label Treatment Period STARTED	42	50
Open-Label Treatment Period COMPLETED	20	24
Open-Label Treatment Period NOT COMPLETED	22	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Tildacerfont Group Tildacerfont 200 mg administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks	Placebo Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks
Double-blind Treatment Period Withdrawal by Subject	1	2
Double-blind Treatment Period Adverse Event	1	0
Double-blind Treatment Period Lost to Follow-up	1	0
Double-blind Treatment Period Protocol Violation	1	0
Open-Label Treatment Period Study Terminated	15	19
Open-Label Treatment Period Withdrawal by Subject	6	5
Open-Label Treatment Period Adverse Event	0	1
Open-Label Treatment Period Physician Decision	1	0
Open-Label Treatment Period Other	0	1

Baseline Characteristics

1 participant did not have the testosterone assessment completed at baseline and this was noted as a protocol deviation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tildacerfont Group n=48 Participants Tildacerfont 200 mg administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks	Placebo n=52 Participants Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks	Total n=100 Participants Total of all reporting groups
Age, Continuous	33.0 years STANDARD_DEVIATION 11.52 • n=48 Participants	32.0 years STANDARD_DEVIATION 12.08 • n=52 Participants	32.5 years STANDARD_DEVIATION 11.77 • n=100 Participants
Sex: Female, Male Female	25 Participants n=48 Participants	28 Participants n=52 Participants	53 Participants n=100 Participants
Sex: Female, Male Male	23 Participants n=48 Participants	24 Participants n=52 Participants	47 Participants n=100 Participants
Race/Ethnicity, Customized Hispanic or Latino	7 Participants n=48 Participants	6 Participants n=52 Participants	13 Participants n=100 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	41 Participants n=48 Participants	44 Participants n=52 Participants	85 Participants n=100 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=48 Participants	2 Participants n=52 Participants	2 Participants n=100 Participants
Race/Ethnicity, Customized Asian	6 Participants n=48 Participants	8 Participants n=52 Participants	14 Participants n=100 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=48 Participants	0 Participants n=52 Participants	3 Participants n=100 Participants
Race/Ethnicity, Customized White	38 Participants n=48 Participants	43 Participants n=52 Participants	81 Participants n=100 Participants
Race/Ethnicity, Customized Other	1 Participants n=48 Participants	1 Participants n=52 Participants	2 Participants n=100 Participants
Females with Child-Bearing Potential	22 Participants n=48 Participants	26 Participants n=52 Participants	48 Participants n=100 Participants
Time Since Congenital adrenal hyperplasia (CAH) Diagnosis	31.2 years STANDARD_DEVIATION 11.58 • n=48 Participants	28.0 years STANDARD_DEVIATION 12.99 • n=52 Participants	29.5 years STANDARD_DEVIATION 12.37 • n=100 Participants
Type of CAH Diagnosis Salt-wasting	36 Participants n=48 Participants	35 Participants n=52 Participants	71 Participants n=100 Participants
Type of CAH Diagnosis Simple Virilizing	12 Participants n=48 Participants	17 Participants n=52 Participants	29 Participants n=100 Participants
17-hydroxyprogesterone (17-OHP)	5642.5 ng/dL STANDARD_DEVIATION 7481.57 • n=48 Participants	5656.6 ng/dL STANDARD_DEVIATION 6995.03 • n=52 Participants	5649.8 ng/dL STANDARD_DEVIATION 7195.84 • n=100 Participants
Androstenedione (A4)	227.2 ng/dL STANDARD_DEVIATION 247.10 • n=48 Participants	222.2 ng/dL STANDARD_DEVIATION 203.28 • n=52 Participants	224.6 ng/dL STANDARD_DEVIATION 224.24 • n=100 Participants
Adrenocorticotropic hormone, corticotropin (ACTH)	176.79 pg/mL STANDARD_DEVIATION 316.658 • n=48 Participants	159.77 pg/mL STANDARD_DEVIATION 190.594 • n=52 Participants	167.94 pg/mL STANDARD_DEVIATION 257.663 • n=100 Participants
Testosterone	256.1 ng/dL STANDARD_DEVIATION 268.67 • n=47 Participants • 1 participant did not have the testosterone assessment completed at baseline and this was noted as a protocol deviation	215.1 ng/dL STANDARD_DEVIATION 231.74 • n=52 Participants • 1 participant did not have the testosterone assessment completed at baseline and this was noted as a protocol deviation	234.5 ng/dL STANDARD_DEVIATION 249.50 • n=99 Participants • 1 participant did not have the testosterone assessment completed at baseline and this was noted as a protocol deviation
Height	162.29 cm STANDARD_DEVIATION 10.151 • n=48 Participants	160.87 cm STANDARD_DEVIATION 10.348 • n=52 Participants	161.55 cm STANDARD_DEVIATION 10.227 • n=100 Participants
Weight	81.56 kg STANDARD_DEVIATION 21.948 • n=48 Participants	82.50 kg STANDARD_DEVIATION 22.004 • n=52 Participants	82.05 kg STANDARD_DEVIATION 21.871 • n=100 Participants
Number of Cardiovascular Risk Factors 0	0 participants n=48 Participants	2 participants n=52 Participants	2 participants n=100 Participants
Number of Cardiovascular Risk Factors 1	7 participants n=48 Participants	1 participants n=52 Participants	8 participants n=100 Participants
Number of Cardiovascular Risk Factors 2	6 participants n=48 Participants	12 participants n=52 Participants	18 participants n=100 Participants
Number of Cardiovascular Risk Factors >2	35 participants n=48 Participants	37 participants n=52 Participants	72 participants n=100 Participants
Homeostatic model assessment of insulin resistance (HOMA-IR)	3.42 units on a scale STANDARD_DEVIATION 2.885 • n=45 Participants • 6 participants did not have the HOMA-IR assessment completed at baseline and this was noted as a protocol deviation	3.22 units on a scale STANDARD_DEVIATION 2.297 • n=49 Participants • 6 participants did not have the HOMA-IR assessment completed at baseline and this was noted as a protocol deviation	3.32 units on a scale STANDARD_DEVIATION 2.583 • n=94 Participants • 6 participants did not have the HOMA-IR assessment completed at baseline and this was noted as a protocol deviation
BMI	30.95 kg/m^2 STANDARD_DEVIATION 7.837 • n=48 Participants	32.03 kg/m^2 STANDARD_DEVIATION 8.301 • n=52 Participants	31.51 kg/m^2 STANDARD_DEVIATION 8.059 • n=100 Participants
Waist Circumference	96.90 cm STANDARD_DEVIATION 17.518 • n=48 Participants	100.07 cm STANDARD_DEVIATION 19.128 • n=52 Participants	98.56 cm STANDARD_DEVIATION 18.357 • n=100 Participants
Testicular adrenal rest tumor (TART) Volume	2.1056 mL STANDARD_DEVIATION 2.32648 • n=8 Participants • Only male participants with a history of TART had baseline value measured.	2.2170 mL STANDARD_DEVIATION 2.32177 • n=5 Participants • Only male participants with a history of TART had baseline value measured.	2.1485 mL STANDARD_DEVIATION 2.22651 • n=13 Participants • Only male participants with a history of TART had baseline value measured.
Hospital Anxiety and Depression Scale (HADs) Total Score	8.1 units on a scale STANDARD_DEVIATION 6.01 • n=48 Participants • 1 participant did not have the HADs assessment completed at baseline and this was noted as a protocol deviation	6.2 units on a scale STANDARD_DEVIATION 4.90 • n=51 Participants • 1 participant did not have the HADs assessment completed at baseline and this was noted as a protocol deviation	7.2 units on a scale STANDARD_DEVIATION 5.52 • n=99 Participants • 1 participant did not have the HADs assessment completed at baseline and this was noted as a protocol deviation

PRIMARY outcome

Timeframe: 24 Weeks

Absolute change from baseline (Day 1) in GC dose in HCe at Week 24. The analysis of absolute change in total daily GC dose in HCe will include data from Weeks 3, 6, 12, 18 and 24 in a mixed model

Outcome measures

Outcome measures
Measure	Tildacerfont Group n=48 Participants Tildacerfont 200 mg administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks	Placebo n=52 Participants Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks
Change in Total Daily GC Dose in Subjects With Classic CAH Over the 24-week, Double Blind, Placebo-Controlled Treatment Period	-5.0 mg Standard Deviation 8.91	-4.3 mg Standard Deviation 9.75

SECONDARY outcome

Timeframe: 24 weeks

Population: Responders are subjects with glucocorticoid dose ≤11 mg/m2/day in HCe and A4 ≤ 1.2x Baseline or A4 ≤ ULN at Week 24.

Proportion of subjects with GC dose ≤11mg/m2/day in HCe and A4 ≤1.2x baseline or A4 ≤ ULN at Week 24

Outcome measures

Outcome measures
Measure	Tildacerfont Group n=48 Participants Tildacerfont 200 mg administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks	Placebo n=52 Participants Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks
Effect of Tildacrfont in Reducing GC Use to Near-physiologic Levels While Maintaining Androgen Control in Subjects With CAH	4 Participants	5 Participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: Responders are subjects with baseline glucocorticoid dose ≤ 35 mg HCe and glucocorticoid dose ≤11 mg/m2/day in HCe and A4 ≤ 1.2x Baseline or A4 ≤ ULN at Week 24.

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

Outcome measures

Outcome measures
Measure	Tildacerfont Group n=19 Participants Tildacerfont 200 mg administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks	Placebo n=25 Participants Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks
Effect of Tildacrfont in Reducing GC Use to Near-physiologic Levels While Maintaining Androgen Control in Subjects With CAH	2 Participants	4 Participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: Responders are subjects with improvement in ≥ 1 baseline cardiovascular risk factor at Week 24.

Proportion of subjects with improvement in at least one cardiovascular risk factor at Week 24

Outcome measures

Outcome measures
Measure	Tildacerfont Group n=48 Participants Tildacerfont 200 mg administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks	Placebo n=50 Participants Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks
Effectiveness in Reducing Cardiovascular Risk in Subjects With CAH	26 Participants	19 Participants

Adverse Events

Tildacerfont Group

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Open Label Extension

Serious events: 2 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tildacerfont Group n=48 participants at risk Tildacerfont 200 mg administered daily via oral tablet for 24 weeks; followed by open label tildacerfont 200 mg for 52 weeks	Placebo n=52 participants at risk Placebo administered daily via oral tablet for 24 weeks	Open Label Extension n=92 participants at risk Open label tildacerfont 200 mg for 52 weeks
Endocrine disorders adrenocortical insufficiency acute	0.00% 0/48 • The study period was expected to be up to 240 weeks in duration (double-blind treatment [24 weeks], open-label treatment [52 weeks], and optional open-label extension [up to the 240th week]), but due to early study termination, the total study period was 205 weeks. No subject entered the optional open label extension. The final safety follow-up was assessed at 30 days after the last dose of study drug for each participant.	0.00% 0/52 • The study period was expected to be up to 240 weeks in duration (double-blind treatment [24 weeks], open-label treatment [52 weeks], and optional open-label extension [up to the 240th week]), but due to early study termination, the total study period was 205 weeks. No subject entered the optional open label extension. The final safety follow-up was assessed at 30 days after the last dose of study drug for each participant.	1.1% 1/92 • The study period was expected to be up to 240 weeks in duration (double-blind treatment [24 weeks], open-label treatment [52 weeks], and optional open-label extension [up to the 240th week]), but due to early study termination, the total study period was 205 weeks. No subject entered the optional open label extension. The final safety follow-up was assessed at 30 days after the last dose of study drug for each participant.
Musculoskeletal and connective tissue disorders intervertebral disc protrusion	0.00% 0/48 • The study period was expected to be up to 240 weeks in duration (double-blind treatment [24 weeks], open-label treatment [52 weeks], and optional open-label extension [up to the 240th week]), but due to early study termination, the total study period was 205 weeks. No subject entered the optional open label extension. The final safety follow-up was assessed at 30 days after the last dose of study drug for each participant.	0.00% 0/52 • The study period was expected to be up to 240 weeks in duration (double-blind treatment [24 weeks], open-label treatment [52 weeks], and optional open-label extension [up to the 240th week]), but due to early study termination, the total study period was 205 weeks. No subject entered the optional open label extension. The final safety follow-up was assessed at 30 days after the last dose of study drug for each participant.	1.1% 1/92 • The study period was expected to be up to 240 weeks in duration (double-blind treatment [24 weeks], open-label treatment [52 weeks], and optional open-label extension [up to the 240th week]), but due to early study termination, the total study period was 205 weeks. No subject entered the optional open label extension. The final safety follow-up was assessed at 30 days after the last dose of study drug for each participant.

Other adverse events

Additional Information

Spruce Clinical Trials

Spruce Biosciences

Phone: 415-655-4169

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place