<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/NCT02994147</url>
  </required_header>
  <id_info>
    <org_study_id>AC-201CR-HA-001</org_study_id>
    <nct_id>NCT02994147</nct_id>
  </id_info>
  <brief_title>A Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy</brief_title>
  <official_title>A Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TWi Biotechnology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TWi Biotechnology, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Repeated joint bleeding leads to hemophilic arthropathy (HA), which manifests with chronic&#xD;
      synovitis, cartilage damage and bony destruction. Currently available treatments of HA,&#xD;
      including analgesics, NSAIDs, and hyaluronic acid, are predominantly directed toward the&#xD;
      symptomatic relief of pain and inflammation, with no or little effect on joint cartilage&#xD;
      degeneration. AC201CR, a control released formulation of AC-201, demonstrates&#xD;
      anti-inflammatory effects by reducing NLRP3 inflammasome assembly. AC-201 is also unique in&#xD;
      that it influences both the anabolism and catabolism of chondrocytes in vitro and has shown&#xD;
      cartilage-sparing properties in animal studies. The study is designed to evaluate the joint&#xD;
      structure-modifying and symptom-relieving effects, safety, and tolerability of AC-201CR in&#xD;
      subjects with HA.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 21, 2017</start_date>
  <completion_date type="Actual">October 2, 2019</completion_date>
  <primary_completion_date type="Actual">April 18, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in IPSG (MRI) score for primary knee</measure>
    <time_frame>24 Weeks</time_frame>
    <description>Knee arthropathy will be evaluated according to the 2012 IPSG (International Prophylaxis Study Group) rating scale. This scale is an additive scale with maximum value up to 17 points, comprising 2 subscores of soft tissue changes (maximum 9 points) and osteochondral changes (maximum 8 points).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in IPSG (MRI) score for non-primary knee</measure>
    <time_frame>24 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in IPSG score by knee</measure>
    <time_frame>48 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in IPSG component scores by knee</measure>
    <time_frame>24 Weeks and 48 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in MRI-measured synovial thickness by knee</measure>
    <time_frame>24 Weeks and 48 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ultrasonographic synovial thickness by knee</measure>
    <time_frame>24 Weeks and 48 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ultrasonographic hyperemia score by knee</measure>
    <time_frame>24 Weeks and 48 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in knee pain (by VAS) by knee</measure>
    <time_frame>4, 12, 24, 28, 36 and 48 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Short Form-36 score</measure>
    <time_frame>24 Weeks and 48 Weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Hemophilic Arthropathy</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period.&#xD;
At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AC-201CR 72mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period.&#xD;
At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo-only control study medication is the same formulation as active treatment without active ingredient</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AC-201CR</intervention_name>
    <description>The investigational product is formulated as controlled-release (CR) tablets</description>
    <arm_group_label>AC-201CR 72mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male age 20 to 65 years, inclusive&#xD;
&#xD;
          2. Diagnosis of Hemophilia A or B&#xD;
&#xD;
          3. Clinical diagnosis of hemophilic arthropathy in the knee(s) for at least 6 months&#xD;
&#xD;
          4. Pettersson score (based on X-ray) of 0 to 4 in at least one knee within 1 year of&#xD;
             screening&#xD;
&#xD;
          5. IPSG (2012) overall score of 3 to 9 (based on MRI) in at least one knee at screening&#xD;
&#xD;
          6. Is able to read, understand, and sign the Informed Consent Form (ICF), communicate&#xD;
             with the investigator, complete study diaries, and understand and comply with protocol&#xD;
             requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Total knee replacement in the primary knee&#xD;
&#xD;
          2. Presence of joint infections in the primary knee&#xD;
&#xD;
          3. Knee surgery within 6 months prior to screening in the primary knee&#xD;
&#xD;
          4. Intra-articular hyaluronic acid (IAHA) or platelet-rich plasma (PRP) injection in the&#xD;
             primary knee within 6 months prior to screening&#xD;
&#xD;
          5. Use of any of the following medications after the screening visit:&#xD;
&#xD;
               1. NSAID injection (oral NSAIDs including COX-2 inhibitors allowed)&#xD;
&#xD;
               2. Glucosamine or chondroitin&#xD;
&#xD;
          6. History of high responder inhibitory antibodies to factor VIII or factor IX clotting&#xD;
             factor, with titer &gt;5 Bethesda units (BU), OR clinical evidence for presence of factor&#xD;
             inhibitor&#xD;
&#xD;
          7. History of rheumatoid arthritis or gouty arthropathy&#xD;
&#xD;
          8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration &gt;2x&#xD;
             the upper limit of laboratory normal range (ULN), or bilirubin &gt;1.5x ULN at screening&#xD;
&#xD;
          9. Positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or TB&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Tri-Service General Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2020</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>Joint Diseases</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/NCT02994147
org study id: AC-201CR-HA-001
nct id: NCT02994147
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Repeated joint bleeding leads to hemophilic arthropathy (HA), which manifests with chronic
      synovitis, cartilage damage and bony destruction. Currently available treatments of HA,
      including analgesics, NSAIDs, and hyaluronic acid, are predominantly directed toward the
      symptomatic relief of pain and inflammation, with no or little effect on joint cartilage
      degeneration. AC201CR, a control released formulation of AC-201, demonstrates
      anti-inflammatory effects by reducing NLRP3 inflammasome assembly. AC-201 is also unique in
      that it influences both the anabolism and catabolism of chondrocytes in vitro and has shown
      cartilage-sparing properties in animal studies. The study is designed to evaluate the joint
      structure-modifying and symptom-relieving effects, safety, and tolerability of AC-201CR in
      subjects with HA.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from baseline in IPSG (MRI) score for primary knee
time frame: 24 Weeks
description: Knee arthropathy will be evaluated according to the 2012 IPSG (International Prophylaxis Study Group) rating scale. This scale is an additive scale with maximum value up to 17 points, comprising 2 subscores of soft tissue changes (maximum 9 points) and osteochondral changes (maximum 8 points).
measure: Change from baseline in IPSG (MRI) score for non-primary knee
time frame: 24 Weeks
measure: Change from baseline in IPSG score by knee
time frame: 48 Weeks
measure: Change from baseline in IPSG component scores by knee
time frame: 24 Weeks and 48 Weeks
measure: Change from baseline in MRI-measured synovial thickness by knee
time frame: 24 Weeks and 48 Weeks
measure: Change from baseline in ultrasonographic synovial thickness by knee
time frame: 24 Weeks and 48 Weeks
measure: Change from baseline in ultrasonographic hyperemia score by knee
time frame: 24 Weeks and 48 Weeks
measure: Change from baseline in knee pain (by VAS) by knee
time frame: 4, 12, 24, 28, 36 and 48 Weeks
measure: Change from baseline in Short Form-36 score
time frame: 24 Weeks and 48 Weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period.
At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study.
arm group label: AC-201CR 72mg
arm group type: Experimental
description: Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period.
At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study.
intervention type: Drug
intervention name: Placebo
description: Placebo-only control study medication is the same formulation as active treatment without active ingredient
arm group label: Placebo
intervention type: Drug
intervention name: AC-201CR
description: The investigational product is formulated as controlled-release (CR) tablets
arm group label: AC-201CR 72mg
criteria: 
gender: Male
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Joint Diseases
sharing ipd: No