21-OHD, Congenital Adrenal Hyperplasia
Conditions
Keywords
Pediatric, CAH, Adrenal Disorder, Congenital Adrenal Hyperplasia
Brief summary
An investigation of the safety and efficacy of tildacerfont in participants with CAH.
Detailed description
This is a Phase 2 open-label study with up to 10 cohorts that will evaluate the safety, efficacy, and PK of different tildacerfont dosing regimens potentially up to 200mg QD for 12 weeks in children with classic CAH, and up to 400mg BID for 4 weeks in children and adults with classic CAH.
Interventions
DRUGTildacerfont
Oral tablet formulation taken once daily in combination with glucocorticoid therapy.
Sponsors
Spruce Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will be assigned to treatment cohorts by age.
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects aged 2+ * Diagnosis of CAH due to 21-hydroxylase deficiency (OHD) and/or elevated 17- hydroxyprogesterone (OHP) requiring ongoing GC replacement since diagnosis * Stable dose of GC replacement for at least 1 month prior to screening
Exclusion criteria
* History of bilateral adrenalectomy or hypopituitarism * Clinically significant unstable medical conditions, illness, or chronic diseases * History of active bleeding disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 12 weeks | To evaluate safety of tildacerfont in participants with CAH as measured by number of subjects with adverse events following dosing by CTCAE version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing | 12 weeks | To determine the efficacy of tildacerfont on disease control or reduction of GC use in participants with classic CAH as measured by number of subjects who achieve a reduction in A4 or reduction in GC dosing during treatment period |
| Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 | 4 weeks | To determine the efficacy of tildacerfont on disease control in participants with classic CAH measured by the number of participants with elevated baseline A4 who achieve reduction in A4 at week 4 |
| Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | 4 weeks or 12 weeks | To determine the efficacy of tildacerfont on disease control in participants with classic CAH measured by the number of participants with elevated baseline A4 who achieve reduction in A4 at week 4 or week 12 |
Countries
United States
Participant flow
Recruitment details
Study was terminated before participants could be enrolled in Cohort 9
Pre-assignment details
Doses in Cohort 3 were determined to be weight-based dose equivalents of \>/= 200 mg QD. Upon completion of the 4-week dosing on participants from Cohorts 4&6, DMC assessed safety data and provided recommendations on dosing for Cohort 5 (initiated either at 300mg or 400mg BID) and for Cohort 7. Following completion of Cohorts 5&7, DMC reviewed safety data made recommendations on whether to proceed to Cohort 8 and at what dose for each participant (either 300mg or 400mg).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Age 11-17 Treatment With Tildacerfont 50 mg daily for 12 consecutive weeks. | 7 |
| Cohort 2: Age 11-17 Treatment With Tildacerfont 200 mg daily for 12 consecutive weeks. | 7 |
| Cohort 3: Age 2-10 Treatment With Tildacerfont 50, 100, or 200 mg daily for 12 consecutive weeks. | 18 |
| Cohort 4: Treatment With Tildacerfont 200 mg twice daily for 4 consecutive weeks. | 2 |
| Cohort 5: Treatment With Tildacerfont 300 or 400 mg twice daily for 4 consecutive weeks. | 6 |
| Cohort 6: Treatment With Tildacerfont 200 mg twice daily for 4 consecutive weeks. | 8 |
| Cohort 7: Treatment With Tildacerfont 200 mg twice daily for 4 consecutive weeks. | 12 |
| Cohort 8: Treatment With Tildacerfont 300 or 400 mg twice daily for 4 consecutive weeks. | 7 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Termination by Sponsor | 2 | 6 | 14 | 2 | 4 | 8 | 11 | 6 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 8: Treatment With Tildacerfont | Cohort 7: Treatment With Tildacerfont | Cohort 6: Treatment With Tildacerfont | Cohort 5: Treatment With Tildacerfont | Cohort 4: Treatment With Tildacerfont | Cohort 3: Age 2-10 Treatment With Tildacerfont | Cohort 2: Age 11-17 Treatment With Tildacerfont | Cohort 1: Age 11-17 Treatment With Tildacerfont | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 15.214 years STANDARD_DEVIATION 1.7192 | 6.882 years STANDARD_DEVIATION 2.5185 | 14.354 years STANDARD_DEVIATION 2.0792 | 26.333 years STANDARD_DEVIATION 8.2635 | 25.125 years STANDARD_DEVIATION 8.8978 | 7.722 years STANDARD_DEVIATION 2.3279 | 14.381 years STANDARD_DEVIATION 2.539 | 13.238 years STANDARD_DEVIATION 1.688 | 12.604 years STANDARD_DEVIATION 6.7977 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 7 Participants | 2 Participants | 1 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 9 Participants | 6 Participants | 3 Participants | 1 Participants | 11 Participants | 5 Participants | 6 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race White | 7 Participants | 12 Participants | 7 Participants | 6 Participants | 0 Participants | 14 Participants | 5 Participants | 7 Participants | 58 Participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 6 Participants | 4 Participants | 1 Participants | 9 Participants | 3 Participants | 7 Participants | 41 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants | 2 Participants | 1 Participants | 9 Participants | 4 Participants | 0 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 | 0 / 18 | 0 / 2 | 0 / 1 | 0 / 5 | 0 / 8 | 0 / 12 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 4 / 7 | 6 / 7 | 18 / 18 | 2 / 2 | 0 / 1 | 3 / 5 | 8 / 8 | 12 / 12 | 2 / 3 | 3 / 4 |
| serious Total, serious adverse events | 0 / 7 | 1 / 7 | 1 / 18 | 0 / 2 | 0 / 1 | 0 / 5 | 0 / 8 | 1 / 12 | 0 / 3 | 0 / 4 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
To evaluate safety of tildacerfont in participants with CAH as measured by number of subjects with adverse events following dosing by CTCAE version 5.0
Time frame: 12 weeks
Population: For Cohorts 5 and 8, the Statistical Analysis Plan pre-specified to analyze the data separately per Cohort, without regard to dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Age 11-17 Treatment With Tildacerfont | Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 4 Participants |
| Cohort 2: Age 11-17 Treatment With Tildacerfont | Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 6 Participants |
| Cohort 3: Age 2-10 Treatment With Tildacerfont | Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 18 Participants |
| Cohort 4: Treatment With Tildacerfont | Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 2 Participants |
| Cohort 5: Treatment With Tildacerfont | Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 3 Participants |
| Cohort 6: Treatment With Tildacerfont | Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 8 Participants |
| Cohort 7: Treatment With Tildacerfont | Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 12 Participants |
| Cohort 8: Treatment With Tildacerfont | Number of Participants With Treatment-emergent Adverse Event (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 5 Participants |
Secondary
Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing
To determine the efficacy of tildacerfont on disease control or reduction of GC use in participants with classic CAH as measured by number of subjects who achieve a reduction in A4 or reduction in GC dosing during treatment period
Time frame: 12 weeks
Population: For Cohorts 5 and 8, the Statistical Analysis Plan pre-specified to analyze the data separately per Cohort, without regard to dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Age 11-17 Treatment With Tildacerfont | Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing | 5 Participants |
| Cohort 2: Age 11-17 Treatment With Tildacerfont | Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing | 4 Participants |
| Cohort 3: Age 2-10 Treatment With Tildacerfont | Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing | 14 Participants |
| Cohort 4: Treatment With Tildacerfont | Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing | 2 Participants |
| Cohort 5: Treatment With Tildacerfont | Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing | 0 Participants |
| Cohort 6: Treatment With Tildacerfont | Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing | 4 Participants |
| Cohort 7: Treatment With Tildacerfont | Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing | 1 Participants |
| Cohort 8: Treatment With Tildacerfont | Proportion of Participants Who Achieve a Reduction in Androstenedione (A4) or Reduction in Glucocorticoid (GC) Dosing | 0 Participants |
Secondary
Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4
To determine the efficacy of tildacerfont on disease control in participants with classic CAH measured by the number of participants with elevated baseline A4 who achieve reduction in A4 at week 4
Time frame: 4 weeks
Population: For Cohorts 5 and 8, the Statistical Analysis Plan pre-specified to analyze the data separately per Cohort, without regard to dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Age 11-17 Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 | 4 Participants |
| Cohort 2: Age 11-17 Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 | 3 Participants |
| Cohort 3: Age 2-10 Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 | 9 Participants |
| Cohort 4: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 | 0 Participants |
| Cohort 5: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 | 1 Participants |
| Cohort 6: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 | 6 Participants |
| Cohort 7: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 | 5 Participants |
| Cohort 8: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 | 0 Participants |
Secondary
Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization
To determine the efficacy of tildacerfont on disease control in participants with classic CAH measured by the number of participants with elevated baseline A4 who achieve reduction in A4 at week 4 or week 12
Time frame: 4 weeks or 12 weeks
Population: For Cohorts 5 and 8, the Statistical Analysis Plan pre-specified to analyze the data separately per Cohort, without regard to dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Age 11-17 Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 12 | 0 Participants |
| Cohort 1: Age 11-17 Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 4 | 1 Participants |
| Cohort 2: Age 11-17 Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 12 | 0 Participants |
| Cohort 2: Age 11-17 Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 4 | 0 Participants |
| Cohort 3: Age 2-10 Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 4 | 1 Participants |
| Cohort 3: Age 2-10 Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 12 | 2 Participants |
| Cohort 4: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 4 | 0 Participants |
| Cohort 4: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 12 | 0 Participants |
| Cohort 5: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 4 | 0 Participants |
| Cohort 5: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 12 | 0 Participants |
| Cohort 6: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 12 | 1 Participants |
| Cohort 6: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 4 | 1 Participants |
| Cohort 7: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 4 | 1 Participants |
| Cohort 7: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 12 | 0 Participants |
| Cohort 8: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 12 | 0 Participants |
| Cohort 8: Treatment With Tildacerfont | Proportion of Participants With Elevated Baseline A4 Who Achieve a Reduction in A4 Who Achieve A4 Normalization | Week 4 | 0 Participants |