<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03257462</url>
  </required_header>
  <id_info>
    <org_study_id>SPR001-201</org_study_id>
    <nct_id>NCT03257462</nct_id>
  </id_info>
  <brief_title>Study of SPR001 in Adults With Classic Congenital Adrenal Hyperplasia</brief_title>
  <official_title>A Phase 2, Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Efficacy of SPR001 in Adults With Classic Congenital Adrenal Hyperplasia (CAH)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spruce Biosciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Spruce Biosciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter Phase 2, multiple dose, dose escalation study to evaluate the safety,&#xD;
      pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SPR001 in adult patients with&#xD;
      classic congenital adrenal hyperplasia (CAH).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 6-week, multiple-dose, dose escalation study of SPR001 for the treatment of adults&#xD;
      with classic CAH. After screening, eligible patients will be enrolled into a 6-week treatment&#xD;
      period followed by a 4-week washout/safety follow-up period.&#xD;
&#xD;
      It is initially planned that up to approximately 18 patients in 2 dose cohorts will be&#xD;
      enrolled. Additional patients or dose groups may be considered based upon specific safety,&#xD;
      PK/PD, and/or efficacy findings, or if an active dose has not yet been reached.&#xD;
&#xD;
      SPR001 will be administered as an oral daily dose. Patients will undergo titration of SPR001&#xD;
      through three escalating dosage strengths at 2-week intervals. Patients will have overnight&#xD;
      PK/PD assessments performed at baseline, which include an pre-dose overnight assessment and a&#xD;
      post-dose overnight assessment for PK/PD following administration of the first dose. At the&#xD;
      end of each 2-week dosing period, patients will return for single overnight visits for&#xD;
      steady-state PK/PD assessments.&#xD;
&#xD;
      A follow-up outpatient visit will occur 30 days after their last dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 26, 2017</start_date>
  <completion_date type="Actual">May 28, 2019</completion_date>
  <primary_completion_date type="Actual">April 15, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of SPR001 in patients with CAH</measure>
    <time_frame>6 weeks</time_frame>
    <description>Incidence of treatment-emergent adverse events; changes from Baseline to End-of-study in clinical laboratory parameters, physical examination findings, vital signs, ECG parameters</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in 17-hydroxyprogesterone</measure>
    <time_frame>6 weeks</time_frame>
    <description>Change in 17-hydroxyprogesterone from Baseline to End-of-study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in pharmacodynamic (PD) markers</measure>
    <time_frame>6 weeks</time_frame>
    <description>Changes in ACTH and androgens from Baseline to End-of-study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>6 weeks</time_frame>
    <description>To evaluate the pharmacokinetic (PK) parameter of maximum plasma concentration (Cmax) of SPR001 in patients with CAH</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve (AUC)</measure>
    <time_frame>6 weeks</time_frame>
    <description>To evaluate the PK parameter of area under the concentration-time curve (AUC) of SPR001 in patients with CAH</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK/PD relationships</measure>
    <time_frame>6 weeks</time_frame>
    <description>To explore the potential relationships between pharmacokinetics and pharmacodynamics</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Congenital Adrenal Hyperplasia</condition>
  <condition>CAH - Congenital Adrenal Hyperplasia</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SPR001</intervention_name>
    <description>SPR001 Capsules</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients age 18 or older.&#xD;
&#xD;
          -  Documented diagnosis of classic CAH due to 21-hydroxylase deficiency&#xD;
&#xD;
          -  Elevated 17-OHP at screening&#xD;
&#xD;
          -  On a stable glucocorticoid replacement regimen for a minimum of 30 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant unstable medical condition, illness, or chronic disease&#xD;
&#xD;
          -  Clinically significant psychiatric disorder.&#xD;
&#xD;
          -  Clinically significant abnormal laboratory finding or assessment&#xD;
&#xD;
          -  History of bilateral adrenalectomy or hypopituitarism&#xD;
&#xD;
          -  Pregnant or nursing females&#xD;
&#xD;
          -  Use of any other investigational drug within 30 days&#xD;
&#xD;
          -  Unable to understand and comply with the study procedures, understand the risks,&#xD;
             and/or unwilling to provide written informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Huang, MD</last_name>
    <role>Study Director</role>
    <affiliation>Spruce Biosciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Richard Auchus, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Spruce Biosciences Clinical Site</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spruce Biosciences Clinical Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spruce Biosciences Clinical Site</name>
      <address>
        <city>Melbourne</city>
        <state>Florida</state>
        <zip>32935</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spruce Biosciences Clinical Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spruce Biosciences Clinical Site</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spruce Biosciences Clinical Site</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spruce Biosciences Clinical Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spruce Biosciences Clinical Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89148</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spruce Biosciences Clinical Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://cahclinicaltrial.com/</url>
    <description>On-line clinical study-related information for patients, including pre-screening questionnaire.</description>
  </link>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>August 15, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>June 24, 2019</last_update_submitted>
  <last_update_submitted_qc>June 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>17-hydroxyprogesterone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adrenal Hyperplasia, Congenital</mesh_term>
    <mesh_term>Adrenogenital Syndrome</mesh_term>
    <mesh_term>Adrenocortical Hyperfunction</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03257462
org study id: SPR001-201
nct id: NCT03257462
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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).
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.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of SPR001 in patients with CAH
time frame: 6 weeks
description: Incidence of treatment-emergent adverse events; changes from Baseline to End-of-study in clinical laboratory parameters, physical examination findings, vital signs, ECG parameters
measure: Change in 17-hydroxyprogesterone
time frame: 6 weeks
description: Change in 17-hydroxyprogesterone from Baseline to End-of-study
measure: Changes in pharmacodynamic (PD) markers
time frame: 6 weeks
description: Changes in ACTH and androgens from Baseline to End-of-study
measure: Maximum plasma concentration (Cmax)
time frame: 6 weeks
description: To evaluate the pharmacokinetic (PK) parameter of maximum plasma concentration (Cmax) of SPR001 in patients with CAH
measure: Area under the concentration-time curve (AUC)
time frame: 6 weeks
description: To evaluate the PK parameter of area under the concentration-time curve (AUC) of SPR001 in patients with CAH
measure: PK/PD relationships
time frame: 6 weeks
description: To explore the potential relationships between pharmacokinetics and pharmacodynamics
arm group label: Cohort A
arm group type: Experimental
description: 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.
arm group label: Cohort B
arm group type: Experimental
description: 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.
arm group label: Cohort C
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: SPR001
description: SPR001 Capsules
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Huang, MD
role: Study Director
affiliation: Spruce Biosciences
last name: Richard Auchus, MD, PhD
role: Principal Investigator
affiliation: University of Michigan
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://cahclinicaltrial.com/
description: On-line clinical study-related information for patients, including pre-screening questionnaire.
responsible party type: Sponsor
mesh term: Adrenal Hyperplasia, Congenital
mesh term: Adrenogenital Syndrome
mesh term: Adrenocortical Hyperfunction
mesh term: Hyperplasia
sharing ipd: No