<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/NCT03837457</url>
  </required_header>
  <id_info>
    <org_study_id>MRG106-11-203</org_study_id>
    <secondary_id>2018-003748-22</secondary_id>
    <nct_id>NCT03837457</nct_id>
  </id_info>
  <brief_title>PRISM: Efficacy and Safety of Cobomarsen (MRG-106) in Subjects With Mycosis Fungoides Who Have Completed the SOLAR Study</brief_title>
  <acronym>PRISM</acronym>
  <official_title>PRISM: An Open-label, Multi-Center Extension Study to Investigate the Efficacy and Safety of Cobomarsen (MRG-106) Following Systemic Treatment in Subjects With Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype, Who Have Completed the SOLAR Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>miRagen Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>miRagen Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The main objective of this clinical trial is to study the efficacy and safety of cobomarsen&#xD;
      (also known as MRG-106) for the treatment of cutaneous T-cell lymphoma (CTCL), mycosis&#xD;
      fungoides (MF) subtype in subjects who have confirmed disease progression following treatment&#xD;
      with vorinostat in the SOLAR clinical study (MRG106-11-201). Cobomarsen is designed to&#xD;
      inhibit the activity of a molecule called miR-155 that may be important to the growth and&#xD;
      survival of MF cancer cells.&#xD;
&#xD;
      The effects of treatment will be measured based on changes in skin lesion severity,&#xD;
      disease-associated symptoms, and quality of life, as well as the length of time that the&#xD;
      subject's disease remains stable or improved, without evidence of disease progression. The&#xD;
      safety and tolerability of cobomarsen will be assessed based on the frequency and severity of&#xD;
      observed side effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Design:&#xD;
&#xD;
      Up to 60 subjects are expected to be enrolled after discontinuation from the SOLAR clinical&#xD;
      study (MRG106-11-201). Cobomarsen will be administered in the clinic by 2-hr intravenous&#xD;
      infusion on Days 1, 3, 5 and 8, and weekly thereafter. Treatment will continue until the&#xD;
      subject becomes intolerant, develops clinically significant side effects, progresses, or the&#xD;
      trial is terminated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study no longer needed because eligible subjects may receive treatment with cobomarsen in a&#xD;
    crossover arm of the SOLAR clinical trial (NCT03713320)&#xD;
  </why_stopped>
  <start_date type="Actual">October 1, 2019</start_date>
  <completion_date type="Actual">July 27, 2020</completion_date>
  <primary_completion_date type="Actual">July 24, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of subjects achieving an objective response of at least 4 months duration (ORR4)</measure>
    <time_frame>Up to approximately 36 months (estimated study duration)</time_frame>
    <description>Based on composite global response criteria including radiological imaging, flow cytometry, and the modified Severity Weighted Assessment Tool (mSWAT).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Up to approximately 36 months (estimated study duration)</time_frame>
    <description>Time from date of first dose of cobomarsen until the date of earliest documented progression or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pruritis Numerical Rating Scale</measure>
    <time_frame>Daily for up to 6 months, then weekly up to approximately 36 months (estimated study duration)</time_frame>
    <description>Measures the patient's degree of itch related to mycosis fungoides based on an 11-point scale (from 0-10), with 0 being no itch and 10 being worst imaginable itch.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skindex-29 Dermatological Survey</measure>
    <time_frame>Monthly, up to approximately 36 months (estimated study duration)</time_frame>
    <description>Measures the effects of skin disease on quality of life based on a 30-item questionnaire. The patient's responses are transformed to a linear scale from 0 to 100 and averaged to determine a subscore in three domains (Symptoms, Emotions and Functioning), as well as a total score. Lower scores indicate a lesser degree of skin disease interference with quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Numerical Rating Scale</measure>
    <time_frame>Daily, for up to 6 months, then weekly up to approximately 36 months (estimated study duration)</time_frame>
    <description>Measures the patient's intensity of pain related to mycosis fungoides based on an 11-point scale (from 0-10), with 0 being no pain and 10 being worst imaginable pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in drug tolerability by Patient Impression of Treatment Side Effects</measure>
    <time_frame>Weekly, up to approximately 36 months (estimated study duration)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of composite global response for responding subjects</measure>
    <time_frame>Up to approximately 36 months (estimated study duration)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete response rate</measure>
    <time_frame>Up to approximately 36 months (estimated study duration)</time_frame>
    <description>Based on composite global response criteria including radiological imaging, flow cytometry, and mSWAT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin disease severity based on modified Severity-weighted Assessment Tool (mSWAT)</measure>
    <time_frame>Monthly, up to approximately 36 months (estimated study duration)</time_frame>
    <description>Measures skin disease severity based on the percentage of skin within each body region with patches, plaques, or tumors. Total scores are calculated by adding the total percent for each category of lesion (patch, plaque, or tumor) and multiplying by a weighting factor. Weighted subtotals are added together to obtain the total score. Lower scores indicate a lower degree of skin disease severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>Up to approximately 36 months (estimated study duration)</time_frame>
    <description>Time from date of first dose of cobomarsen until the earliest date of confirmed progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to approximately 36 months (estimated study duration)</time_frame>
    <description>Time from date of first dose of cobomarsen until the date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0</measure>
    <time_frame>Up to approximately 36 months (estimated study duration)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration of cobomarsen</measure>
    <time_frame>Day 1, Day 29 and monthly or every other month thereafter until End of Treatment visit, up to approximately 36 months (estimated study duration)</time_frame>
    <description>Sparse pharmacokinetic samples will be collected to monitor for accumulation of cobomarsen.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of participants with anti-drug antibody generation</measure>
    <time_frame>Up to approximately 36 months (estimated study duration)</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Cutaneous T-Cell Lymphoma/Mycosis Fungoides</condition>
  <arm_group>
    <arm_group_label>Cobomarsen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cobomarsen</intervention_name>
    <description>At least weekly intravenous infusions of cobomarsen (282 mg) throughout study treatment period</description>
    <arm_group_label>Cobomarsen</arm_group_label>
    <other_name>MRG-106</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Must have participated in the comparator arm of the SOLAR clinical trial and completed&#xD;
             the study (confirmed disease progression).&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Sézary syndrome or mycosis fungoides with B2 involvement, defined as documented&#xD;
             history of B2 and/or B2 staging at screening.&#xD;
&#xD;
          -  Evidence of large cell transformation.&#xD;
&#xD;
          -  Visceral involvement related to MF at screening.&#xD;
&#xD;
          -  Unresolved toxicities from prior vorinostat treatment, defined as having not resolved&#xD;
             to CTCAE v5.0 grade 0 or 1.&#xD;
&#xD;
          -  Any CTCL systemic therapy after completion of the SOLAR study and prior to Day 1 for&#xD;
             PRISM.&#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>Diana M. Escolar, MD, FAAN</last_name>
    <role>Study Director</role>
    <affiliation>miRagen Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University and Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington/Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>B3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Andre, CHU de Bordeaux</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint-Louis</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Charles Nicolle, CHU de Rouen</name>
      <address>
        <city>Rouen</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Italy</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>February 8, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>November 17, 2020</last_update_submitted>
  <last_update_submitted_qc>November 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PRISM</keyword>
  <keyword>Cutaneous T-cell Lymphoma</keyword>
  <keyword>CTCL</keyword>
  <keyword>Mycosis Fungoides</keyword>
  <keyword>Lymphoma</keyword>
  <keyword>Lymphoma, T-cell</keyword>
  <keyword>Lymphoma, T-cell, cutaneous</keyword>
  <keyword>Lymphoma, Non-Hodgkin</keyword>
  <keyword>Lymphoproliferative Disorders</keyword>
  <keyword>Lymphatic Diseases</keyword>
  <keyword>Immunoproliferative Disorders</keyword>
  <keyword>Immune System Diseases</keyword>
  <keyword>Neoplasms</keyword>
  <keyword>MicroRNAs</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycoses</mesh_term>
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
    <mesh_term>Mycosis Fungoides</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Cutaneous</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>July 28, 2021</submitted>
    <returned>August 20, 2021</returned>
    <submitted>March 29, 2022</submitted>
    <returned>April 25, 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/NCT03837457
org study id: MRG106-11-203
secondary id: 2018-003748-22
nct id: NCT03837457
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main objective of this clinical trial is to study the efficacy and safety of cobomarsen
      (also known as MRG-106) for the treatment of cutaneous T-cell lymphoma (CTCL), mycosis
      fungoides (MF) subtype in subjects who have confirmed disease progression following treatment
      with vorinostat in the SOLAR clinical study (MRG106-11-201). Cobomarsen is designed to
      inhibit the activity of a molecule called miR-155 that may be important to the growth and
      survival of MF cancer cells.

      The effects of treatment will be measured based on changes in skin lesion severity,
      disease-associated symptoms, and quality of life, as well as the length of time that the
      subject's disease remains stable or improved, without evidence of disease progression. The
      safety and tolerability of cobomarsen will be assessed based on the frequency and severity of
      observed side effects.
Study Design:

      Up to 60 subjects are expected to be enrolled after discontinuation from the SOLAR clinical
      study (MRG106-11-201). Cobomarsen will be administered in the clinic by 2-hr intravenous
      infusion on Days 1, 3, 5 and 8, and weekly thereafter. Treatment will continue until the
      subject becomes intolerant, develops clinically significant side effects, progresses, or the
      trial is terminated.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of subjects achieving an objective response of at least 4 months duration (ORR4)
time frame: Up to approximately 36 months (estimated study duration)
description: Based on composite global response criteria including radiological imaging, flow cytometry, and the modified Severity Weighted Assessment Tool (mSWAT).
measure: Progression-free survival
time frame: Up to approximately 36 months (estimated study duration)
description: Time from date of first dose of cobomarsen until the date of earliest documented progression or death from any cause.
measure: Pruritis Numerical Rating Scale
time frame: Daily for up to 6 months, then weekly up to approximately 36 months (estimated study duration)
description: Measures the patient's degree of itch related to mycosis fungoides based on an 11-point scale (from 0-10), with 0 being no itch and 10 being worst imaginable itch.
measure: Skindex-29 Dermatological Survey
time frame: Monthly, up to approximately 36 months (estimated study duration)
description: Measures the effects of skin disease on quality of life based on a 30-item questionnaire. The patient's responses are transformed to a linear scale from 0 to 100 and averaged to determine a subscore in three domains (Symptoms, Emotions and Functioning), as well as a total score. Lower scores indicate a lesser degree of skin disease interference with quality of life.
measure: Pain Numerical Rating Scale
time frame: Daily, for up to 6 months, then weekly up to approximately 36 months (estimated study duration)
description: Measures the patient's intensity of pain related to mycosis fungoides based on an 11-point scale (from 0-10), with 0 being no pain and 10 being worst imaginable pain.
measure: Difference in drug tolerability by Patient Impression of Treatment Side Effects
time frame: Weekly, up to approximately 36 months (estimated study duration)
measure: Duration of composite global response for responding subjects
time frame: Up to approximately 36 months (estimated study duration)
measure: Complete response rate
time frame: Up to approximately 36 months (estimated study duration)
description: Based on composite global response criteria including radiological imaging, flow cytometry, and mSWAT.
measure: Skin disease severity based on modified Severity-weighted Assessment Tool (mSWAT)
time frame: Monthly, up to approximately 36 months (estimated study duration)
description: Measures skin disease severity based on the percentage of skin within each body region with patches, plaques, or tumors. Total scores are calculated by adding the total percent for each category of lesion (patch, plaque, or tumor) and multiplying by a weighting factor. Weighted subtotals are added together to obtain the total score. Lower scores indicate a lower degree of skin disease severity.
measure: Time to progression
time frame: Up to approximately 36 months (estimated study duration)
description: Time from date of first dose of cobomarsen until the earliest date of confirmed progression.
measure: Overall survival
time frame: Up to approximately 36 months (estimated study duration)
description: Time from date of first dose of cobomarsen until the date of death from any cause.
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
time frame: Up to approximately 36 months (estimated study duration)
measure: Plasma concentration of cobomarsen
time frame: Day 1, Day 29 and monthly or every other month thereafter until End of Treatment visit, up to approximately 36 months (estimated study duration)
description: Sparse pharmacokinetic samples will be collected to monitor for accumulation of cobomarsen.
measure: Number of participants with anti-drug antibody generation
time frame: Up to approximately 36 months (estimated study duration)
arm group label: Cobomarsen
arm group type: Experimental
intervention type: Drug
intervention name: Cobomarsen
description: At least weekly intravenous infusions of cobomarsen (282 mg) throughout study treatment period
arm group label: Cobomarsen
other name: MRG-106
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Diana M. Escolar, MD, FAAN
role: Study Director
affiliation: miRagen Therapeutics, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: France
country: United States
country: Italy
country: Spain
country: United Kingdom
responsible party type: Sponsor
mesh term: Mycoses
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Mycosis Fungoides
mesh term: Lymphoma, T-Cell, Cutaneous
sharing ipd: No
submitted: July 28, 2021
returned: August 20, 2021
submitted: March 29, 2022
returned: April 25, 2022