Study of SPR001 in Adults With Classic Congenital Adrenal Hyperplasia

Study Overview
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Brief Summary
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This is a multicenter Phase 2, multiple dose, dose escalation study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SPR001 in adult patients with classic congenital adrenal hyperplasia (CAH).

Detailed Description
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This is a 6-week, multiple-dose, dose escalation study of SPR001 for the treatment of adults with classic CAH. After screening, eligible patients will be enrolled into a 6-week treatment period followed by a 4-week washout/safety follow-up period. It is initially planned that up to approximately 18 patients in 2 dose cohorts will be enrolled. Additional patients or dose groups may be considered based upon specific safety, PK/PD, and/or efficacy findings, or if an active dose has not yet been reached. SPR001 will be administered as an oral daily dose. Patients will undergo titration of SPR001 through three escalating dosage strengths at 2-week intervals. Patients will have overnight PK/PD assessments performed at baseline, which include an pre-dose overnight assessment and a post-dose overnight assessment for PK/PD following administration of the first dose. At the end of each 2-week dosing period, patients will return for single overnight visits for steady-state PK/PD assessments. A follow-up outpatient visit will occur 30 days after their last dose.

Official Title
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A Phase 2, Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Efficacy of SPR001 in Adults With Classic Congenital Adrenal Hyperplasia (CAH)

Conditions
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Congenital Adrenal Hyperplasia, CAH - Congenital Adrenal Hyperplasia

Intervention / Treatment
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* Drug: SPR001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients age 18 or older. Documented diagnosis of classic CAH due to 21-hydroxylase deficiency Elevated 17-OHP at screening On a stable glucocorticoid replacement regimen for a minimum of 30 days Exclusion Criteria: Clinically significant unstable medical condition, illness, or chronic disease Clinically significant psychiatric disorder. Clinically significant abnormal laboratory finding or assessment History of bilateral adrenalectomy or hypopituitarism Pregnant or nursing females Use of any other investigational drug within 30 days Unable to understand and comply with the study procedures, understand the risks, and/or unwilling to provide written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>The first cohort of 9 patients will be administered SPR001 at dose strength of Dose A daily for 2 weeks, and escalating through Dose B per day for 2 weeks and Dose C per day for 2 weeks. | Drug: SPR001<br>* SPR001 Capsules<br>|
| Experimental: Cohort B<br>Cohort B will begin enrollment after Cohort A has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort B will be determined by an interim review of safety and PK/PD data from from Cohort A. | Drug: SPR001<br>* SPR001 Capsules<br>|
| Experimental: Cohort C<br>Cohort C will begin enrollment after Cohort B has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort C will be determined by an interim review of safety and PK/PD data from from Cohort A and B. | Drug: SPR001<br>* SPR001 Capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of SPR001 in patients with CAH | Incidence of treatment-emergent adverse events; changes from Baseline to End-of-study in clinical laboratory parameters, physical examination findings, vital signs, ECG parameters | 6 weeks | 
| Change in 17-hydroxyprogesterone | Change in 17-hydroxyprogesterone from Baseline to End-of-study | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in pharmacodynamic (PD) markers | Changes in ACTH and androgens from Baseline to End-of-study | 6 weeks | 
| Maximum plasma concentration (Cmax) | To evaluate the pharmacokinetic (PK) parameter of maximum plasma concentration (Cmax) of SPR001 in patients with CAH | 6 weeks | 
| Area under the concentration-time curve (AUC) | To evaluate the PK parameter of area under the concentration-time curve (AUC) of SPR001 in patients with CAH | 6 weeks | 
| PK/PD relationships | To explore the potential relationships between pharmacokinetics and pharmacodynamics | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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17-hydroxyprogesterone