<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/NCT04489511</url>
  </required_header>
  <id_info>
    <org_study_id>STG-001-2a</org_study_id>
    <nct_id>NCT04489511</nct_id>
  </id_info>
  <brief_title>Study of STG-001 in Subjects With Stargardt Disease</brief_title>
  <official_title>A Phase 2a Study of the Safety, Pharmacokinetics and Pharmacodynamics of STG-001 in Subjects With Stargardt Disease (STGD1) Caused by Autosomal Recessive Mutation in ATP Binding Cassette Subfamily A Member 4 (ABCA4) Gene</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stargazer Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stargazer Pharmaceuticals, Inc.</source>
  <oversight_info>
    <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 an open-label, multicenter study in subjects with Stargardt disease, comparing 2&#xD;
      doses of STG-001 with regard to safety, pharmacokinetics and pharmacodynamics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, multicenter, active treatment study in approximately 12 subjects aged&#xD;
      18 to 55 years (inclusive) with STGD1, genotyped with a minimum of two ABCA4 gene mutations.&#xD;
      Treatment course of STG-001 at Dose 1 (Cohort 1) or Dose 2 (Cohort 2) testing doses will be&#xD;
      administered once daily for 28 days. Cohorts will run in parallel. Subjects will receive&#xD;
      their designated dose daily for 28 days and be monitored for safety measures during the&#xD;
      dosing period and for an additional 28 days after dosing (through Day 56).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Actual">April 24, 2021</completion_date>
  <primary_completion_date type="Actual">April 24, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety events and Tolerability of STG-001 from baseline to 28 days: adverse events</measure>
    <time_frame>From baseline to 28 days</time_frame>
    <description>Safety and tolerability of 28 days of daily dosing of 2 doses of STG-001 assessed by Incidence and/or clinically significant changes of a combination of ocular and non-ocular adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of STG-001 maximum plasma concentration (Cmax) at Day 28</measure>
    <time_frame>From baseline to 28 days</time_frame>
    <description>Cmax of 2 doses of STG-001 after 28 days of daily dosing of STG-001 assessed by a validated STG-001 assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of STG-001 area under the curve (AUC) at Day 28</measure>
    <time_frame>From baseline to 28 days</time_frame>
    <description>Exposure to STG-001 as assessed by calculated AUC of 2 doses of STG-001 after 28 days of daily dosing of STG-001</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics (PD) of STG-001 change in plasma Retinol-Binding Protein 4 (RBP4) at Day 28</measure>
    <time_frame>From baseline to 28 days</time_frame>
    <description>Change in Plasma RBP4 levels from baseline to Day 28 with 2 doses of STG-001 after 28 days of daily dosing of STG-001</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Stargardt Disease-1</condition>
  <arm_group>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>STG-001 given orally at Dose 1 once a day for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>STG-001 given orally at Dose 2 once a day for 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>STG-001</intervention_name>
    <description>Dose 1 or Dose 2 of STG-001 will be administered daily for 28 days to compare safety, pharmacokinetics and pharmacodynamics in Stargardt disease subjects.</description>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_label>Dose 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Understand the study procedures and agree to participate by providing written informed&#xD;
             consent.&#xD;
&#xD;
          2. STGD1 caused by autosomal recessive mutation in the ABCA4 gene (i.e. at least 2&#xD;
             mutations), confirmed genotypically by a fully accredited certified central genotyping&#xD;
             laboratory.&#xD;
&#xD;
          3. 18 to 55 years of age inclusive.&#xD;
&#xD;
          4. Negative pregnancy testing for women of childbearing potential and highly effective&#xD;
             double barrier contraception before, during, and for a period after study treatment as&#xD;
             described in the clinical protocol.&#xD;
&#xD;
          5. Primary study eye must have at least one well-demarcated area of significantly reduced&#xD;
             autofluorescence as imaged by fundus autofluorescence (FAF)&#xD;
&#xD;
          6. In at least one eye and in the same eye:&#xD;
&#xD;
               1. ETDRS BCVA of less than or equal to 0.4 logMAR (≤68 letters; 20/50 Snellen&#xD;
                  equivalent) and greater than or equal to 1.3 logMAR (≥19 letters; 20/400 Snellen&#xD;
                  equivalent); and&#xD;
&#xD;
               2. Clinical evidence of a macular lesion phenotypically consistent with Stargardt&#xD;
                  Disease&#xD;
&#xD;
          7. Naïve to investigational treatment for STGD1 with no history of gene therapy, stem&#xD;
             cell therapy, surgical implantation of prosthetic retinal chips or intravitreal or&#xD;
             sub-retinal injections. History of experimental oral therapy is allowed if it occurred&#xD;
             greater than 3 months prior to Screening.&#xD;
&#xD;
          8. Primary study eye must have clear ocular media and adequate pupillary dilation,&#xD;
             including no allergy to dilating eyedrops, to permit good quality retinal imaging.&#xD;
&#xD;
          9. In good general health, aside from STGD1, as judged by Investigator.&#xD;
&#xD;
         10. Willing and able to comply with the protocol, including attending assessment visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The subject is an employee of the Sponsor or study site or immediate family member&#xD;
             (e.g., spouse, parent, child, sibling) of the Sponsor or study site.&#xD;
&#xD;
          2. Use of prescription or nonprescription drugs and dietary supplements within 7 days or&#xD;
             5 half-lives (whichever is longer) prior to Day 1 first dose. Herbal supplements and&#xD;
             HRT must be discontinued 7 days prior to Day 1 first dose.&#xD;
&#xD;
          3. Presence of any concurrent ocular disease that would affect study outcomes (e.g.,&#xD;
             severe cataracts; subjects can be enrolled 3 months after successful cataract&#xD;
             surgery).&#xD;
&#xD;
          4. Presence of any meaningful retinopathy/maculopathy/atrophy other than as a result of&#xD;
             STGD1 in either eye as determined by the Investigator.&#xD;
&#xD;
          5. Has taken non-approved items (supplement containing vitamin A or beta-carotene,&#xD;
             liver-based products, or prescription oral retinoid medications) within 30 days of&#xD;
             Screening.&#xD;
&#xD;
          6. Use of medications that may interact with Vitamin A metabolism within 60 days of&#xD;
             Screening.&#xD;
&#xD;
          7. Participation in an oral interventional study of a vitamin A derivative up to 3 months&#xD;
             prior to Screening.&#xD;
&#xD;
          8. The subject had a history of vitamin A deficiency as defined based upon serum values&#xD;
             less than 20 mcg/dl (0.7 μmol/L) or clinical signs during slit lamp examination&#xD;
             (conjunctival or corneal xerosis; Bitot's spots; corneal ulcers or scarring not due to&#xD;
             trauma or other secondary causes).&#xD;
&#xD;
          9. Presence of significant cardiovascular or cerebrovascular disease, including stroke,&#xD;
             within 12 months of entry.&#xD;
&#xD;
         10. Has a clinically significant abnormal electrocardiogram (ECG), or has a corrected QT&#xD;
             interval (QTc) that is 450 ms or greater.&#xD;
&#xD;
         11. Resting heart rate outside specified limits (&lt; 40/minute, &gt; 100/min) upon repeated&#xD;
             measurement.&#xD;
&#xD;
         12. History of diabetes, hepatitis, pancreatitis, cirrhosis, liver failure, uncontrolled&#xD;
             thyroid disease or hypervitaminosis A.&#xD;
&#xD;
         13. Any intraocular surgery or thermal laser within 3 months of trial entry. Any prior&#xD;
             thermal laser in the macular region.&#xD;
&#xD;
         14. Any major surgical procedure within one month of Screening or planned or anticipated&#xD;
             surgery during the study period.&#xD;
&#xD;
         15. Women who are pregnant, nursing, or planning to become pregnant during the study&#xD;
             period.&#xD;
&#xD;
         16. Uncontrolled blood pressure outside specified limits (90 mm Hg &gt; Systolic &gt; 140 mm Hg&#xD;
             and/or 40 mm Hg &gt; Diastolic &gt; 90 mm Hg) upon repeated measurement.&#xD;
&#xD;
         17. Clinically significant abnormal lab results at Screening, including liver function&#xD;
             test (aspartate transaminase, alanine transaminase, bilirubin and alkaline&#xD;
             phosphatase) greater than 1.5 x the upper limit of normal (ULN).&#xD;
&#xD;
         18. Actively participating in an investigational therapy study or have received any&#xD;
             investigational therapy within 60 days of Screening or 5 half-lives, whichever is&#xD;
             longer.&#xD;
&#xD;
         19. Known serious allergies to the fluorescein dye used to measure intraocular pressure,&#xD;
             ocular dilating drops, topical ocular anesthetic, components of the STG-001&#xD;
             formulation or any history of anaphylaxis reaction.&#xD;
&#xD;
         20. In the Investigator's assessment, any acute or chronic medical condition, psychiatric&#xD;
             condition, physical examination finding or laboratory abnormality that might increase&#xD;
             the risk associated with study participation or administration of study treatment or&#xD;
             interfere with the interpretation of study results.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Prinicpal Investigator, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Study Site Director</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Associated Retina Consultants</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vitreo Retinal Associates, P.A.</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Casey Eye Institute - OHSU</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Eye Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Foundation of Southwest</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>April 24, 2021</last_update_submitted>
  <last_update_submitted_qc>April 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stargardt Disease</mesh_term>
    <mesh_term>Macular Degeneration</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>February 21, 2022</submitted>
    <returned>March 15, 2022</returned>
    <submitted>March 22, 2022</submitted>
    <returned>April 12, 2022</returned>
  </pending_results>
  <!-- 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/NCT04489511
org study id: STG-001-2a
nct id: NCT04489511
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, multicenter study in subjects with Stargardt disease, comparing 2
      doses of STG-001 with regard to safety, pharmacokinetics and pharmacodynamics.
This is an open-label, multicenter, active treatment study in approximately 12 subjects aged
      18 to 55 years (inclusive) with STGD1, genotyped with a minimum of two ABCA4 gene mutations.
      Treatment course of STG-001 at Dose 1 (Cohort 1) or Dose 2 (Cohort 2) testing doses will be
      administered once daily for 28 days. Cohorts will run in parallel. Subjects will receive
      their designated dose daily for 28 days and be monitored for safety measures during the
      dosing period and for an additional 28 days after dosing (through Day 56).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety events and Tolerability of STG-001 from baseline to 28 days: adverse events
time frame: From baseline to 28 days
description: Safety and tolerability of 28 days of daily dosing of 2 doses of STG-001 assessed by Incidence and/or clinically significant changes of a combination of ocular and non-ocular adverse events
measure: Pharmacokinetics (PK) of STG-001 maximum plasma concentration (Cmax) at Day 28
time frame: From baseline to 28 days
description: Cmax of 2 doses of STG-001 after 28 days of daily dosing of STG-001 assessed by a validated STG-001 assay
measure: Pharmacokinetics (PK) of STG-001 area under the curve (AUC) at Day 28
time frame: From baseline to 28 days
description: Exposure to STG-001 as assessed by calculated AUC of 2 doses of STG-001 after 28 days of daily dosing of STG-001
measure: Pharmacodynamics (PD) of STG-001 change in plasma Retinol-Binding Protein 4 (RBP4) at Day 28
time frame: From baseline to 28 days
description: Change in Plasma RBP4 levels from baseline to Day 28 with 2 doses of STG-001 after 28 days of daily dosing of STG-001
arm group label: Dose 1
arm group type: Experimental
description: STG-001 given orally at Dose 1 once a day for 28 days
arm group label: Dose 2
arm group type: Experimental
description: STG-001 given orally at Dose 2 once a day for 28 days
intervention type: Drug
intervention name: STG-001
description: Dose 1 or Dose 2 of STG-001 will be administered daily for 28 days to compare safety, pharmacokinetics and pharmacodynamics in Stargardt disease subjects.
arm group label: Dose 1
arm group label: Dose 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Prinicpal Investigator, MD
role: Principal Investigator
affiliation: Study Site Director
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Stargardt Disease
mesh term: Macular Degeneration
sharing ipd: No
submitted: February 21, 2022
returned: March 15, 2022
submitted: March 22, 2022
returned: April 12, 2022