<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/NCT02210468</url>
  </required_header>
  <id_info>
    <org_study_id>Cyt300-01</org_study_id>
    <nct_id>NCT02210468</nct_id>
  </id_info>
  <brief_title>APIC-CF Therapy for Mild to Moderate Osteoarthritis of the Knee</brief_title>
  <official_title>A Phase I/II, Multicenter, Double-Blind, Placebo-controlled Safety and Efficacy Study to Evaluate APIC-CF Therapy for Mild to Moderate Primary Osteoarthritis of the Knee</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cytonics Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cytonics Corporation</source>
  <brief_summary>
    <textblock>
      The mechanism of Osteoarthritis (OA) is complex, however the investigators know that&#xD;
      cartilage breakdown follows changes in certain cells in the cartilage called chondrocytes,&#xD;
      leading to proteases that break down cartilage. There is a protein in the human blood called&#xD;
      alpha-2-macroglobulin that can trap these proteases and prevent the breakdown of cartilage.&#xD;
      Cytonics developed a device that use the patient's own blood to remove all cells and&#xD;
      concentrate alpha-2-macroglobulin to be injected in the painful knee due to osteoarthritis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2015</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">July 2016</primary_completion_date>
  <phase>Phase 1/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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction in pain after 8 weeks</measure>
    <time_frame>8 weeks</time_frame>
    <description>Statistically significant reduction in pain after 8 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reduction in pain while walking at 8 weeks</measure>
    <time_frame>8 weeks</time_frame>
    <description>Statistically significant reduction in pain while walking after 8 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduction in pain after 2 weeks</measure>
    <time_frame>2 weeks</time_frame>
    <description>Statistically significant reduction in pain after 2 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in pain while walking at 2 weeks</measure>
    <time_frame>2 weeks</time_frame>
    <description>Statistically significant reduction in pain while walking after 2 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in pain at 24 weeks</measure>
    <time_frame>24 weeks</time_frame>
    <description>Statistically significant reduction in pain after 24 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in pain while walking after 24 weeks</measure>
    <time_frame>24 week</time_frame>
    <description>Statistically significant reduction in pain while walking after 24 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Pain</condition>
  <condition>Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>APIC-CF 4cc,</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>APIC-CF 4cc, once at first day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>APIC-CF, 2cc</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>APIC-CF, 2cc, one at first day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>APIC-CF, 4 cc</intervention_name>
    <arm_group_label>APIC-CF 4cc,</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>APIC-CF, 2 cc</intervention_name>
    <arm_group_label>APIC-CF, 2cc</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Comparator: Saline</intervention_name>
    <description>Placebo Comparator: Saline</description>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patient provides signed written informed consent&#xD;
&#xD;
          2. The patient is willing and able to complete effectiveness and safety questionnaires&#xD;
             and is able to read and understand study instructions in English.&#xD;
&#xD;
          3. Patient is a male or female aged between 21 - 70 years of age at the time of informed&#xD;
             consent.&#xD;
&#xD;
          4. Patient is ambulatory (assistive devices allowed if used 4 weeks or more prior to&#xD;
             Screening).&#xD;
&#xD;
          5. Patient has symptomatic OA in the target knee&#xD;
&#xD;
          6. Patient has a radiographic confirmation of OA at the target knee prior to screening&#xD;
             with a grade II or III score on the K-L grading scale (Kellgren, 1957)using&#xD;
             radiographs performed within 24 weeks of Screening&#xD;
&#xD;
          7. The patient has knee pain as demonstrated by a score of ≤3 on the KOOS pain subscale&#xD;
&#xD;
          8. The patient has venous access sufficient for APIC-CF production&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The patient has any of the following:&#xD;
&#xD;
               -  Grade 4 score on the K-L grading scale for the target knee&#xD;
&#xD;
               -  Grade 3 score on the K-L grading scale and exhibits at least one Grade 4&#xD;
                  characteristic (large osteophytes, marked narrowing of joint space, severe&#xD;
                  sclerosis, or definite deformity of bone contour).&#xD;
&#xD;
               -  Acute fracture of the lower limb.&#xD;
&#xD;
          2. Medical history of severe bone disease (e.g., osteoporosis, osteonecrosis, joint&#xD;
             deformity, instability, or septic arthritis).&#xD;
&#xD;
          3. The patient is categorized as grossly obese, defined as body mass index (BMI) greater&#xD;
             than 35 kg/m2&#xD;
&#xD;
          4. Hemoglobin values &lt;11 g/dL&#xD;
&#xD;
          5. Pregnant or breastfeeding women&#xD;
&#xD;
          6. Has clinically apparent tense effusion of the target knee.&#xD;
&#xD;
          7. Has had chondrocyte transplantation or reconstruction of ligaments in the target knee.&#xD;
&#xD;
          8. Has received an intra-articular injection(s) into any joint (e.g., corticosteroids or&#xD;
             chondroprotective agents) within 60 days prior to Screening. Subjects receiving a&#xD;
             corticosteroid injection during the study will be withdrawn from the study.&#xD;
&#xD;
          9. Has had surgery to the target knee within 12 months or arthroscopy of the target knee&#xD;
             within 90 days prior to Screening.&#xD;
&#xD;
         10. Has an inflammatory disease of either knee other than OA (e.g., rheumatoid arthri&#xD;
             septic arthritis).&#xD;
&#xD;
         11. Has another disease that can affect the health of the knee (e.g., chronic&#xD;
             hemochromatosis; sickle cell anemia; arthropathies of systemic diseases such as&#xD;
             chondrocalcinosis, gout, pseudogout, psoriasis, hemophilia, and infectious diseases of&#xD;
             the joints).&#xD;
&#xD;
         12. Has significant joint infection in the target knee or inflammatory or skin disorder in&#xD;
             the injection area of the target knee.&#xD;
&#xD;
         13. Septic arthritis in any joints within 1 year prior to screening;&#xD;
&#xD;
         14. Has fibromyalgia, anserine bursitis, lumbar radiculopathy, neurogenic or vascular&#xD;
             claudication, vascular insufficiency of lower limbs, or peripheral neuropathy severe&#xD;
             enough to interfere with the study evaluations.&#xD;
&#xD;
         15. Patella femoral instability&#xD;
&#xD;
         16. Patients with a history of cartilage allograft, autograft or microfracture in the&#xD;
             study knee&#xD;
&#xD;
         17. Patients with a history of any type of blood coagulation or bleeding disorder,&#xD;
             currently taking warfarin or other parental anticoagulant therapy or history of DVT/PE&#xD;
             during &lt;1 year of Screening.&#xD;
&#xD;
         18. Has a systemic or other disease or significant liver function test result from&#xD;
             screening that, in the opinion of the investigator, would interfere with study&#xD;
             evaluation or have an impact on the balance of benefits and risks of study treatment.&#xD;
&#xD;
         19. Diseases that may interfere:&#xD;
&#xD;
               -  type 1 diabetes&#xD;
&#xD;
               -  immunodeficiency syndrome&#xD;
&#xD;
               -  significant cardiovascular, renal, or liver disease&#xD;
&#xD;
               -  severe anemia&#xD;
&#xD;
               -  severe thrombocytopenia&#xD;
&#xD;
               -  severe infectious disease with or without fever.&#xD;
&#xD;
               -  any significant chronic skin disorders, active skin or soft tissue infection that&#xD;
                  could interfere with the evaluation of the injection site.&#xD;
&#xD;
               -  mal-alignment/deformity of the leg&#xD;
&#xD;
               -  active asthma that may require periodic treatment with steroids during the study&#xD;
                  period&#xD;
&#xD;
               -  active malignancy receiving treatment, or prior history of any malignancy, with&#xD;
                  the exception of basal cell carcinoma of the skin treated more than 1 year ago&#xD;
&#xD;
         20. Patients with psychiatric or neurological disorders including cognitive impairment or&#xD;
             inability to provide informed consent&#xD;
&#xD;
         21. Incarcerated or confined patients&#xD;
&#xD;
         22. Medical-legal, personal injury, ongoing litigation or worker's compensation claim&#xD;
&#xD;
         23. History of drug abuse&#xD;
&#xD;
         24. Use of investigational drug, device, or biologic within 12 weeks of screening&#xD;
&#xD;
         25. Any condition that, in the opinion of the investigator, might interfere with the&#xD;
             evaluation of the study objectives.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Gaetano Scuderi, MD</last_name>
    <phone>561-575-4451</phone>
    <phone_ext>1</phone_ext>
    <email>scuderimd@aol.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>IRC Clinical</name>
      <address>
        <city>Townsend</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kendra Barton, RN, BSN</last_name>
      <phone>443-275-1599</phone>
      <email>kendra.barton@ircclinical.com</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <last_update_submitted>August 19, 2015</last_update_submitted>
  <last_update_submitted_qc>August 19, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 21, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Osteoarthritis</keyword>
  <keyword>Protease Inhibitors</keyword>
  <keyword>Alpha-2-macroglobulin</keyword>
  <keyword>Autologous treatment</keyword>
  <keyword>APIC-CF</keyword>
  <keyword>Pain due to Mild to Moderate osteoarthritis (OA) of the knee</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <!-- 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/NCT02210468
org study id: Cyt300-01
nct id: NCT02210468
lead sponsor: 
The mechanism of Osteoarthritis (OA) is complex, however the investigators know that
      cartilage breakdown follows changes in certain cells in the cartilage called chondrocytes,
      leading to proteases that break down cartilage. There is a protein in the human blood called
      alpha-2-macroglobulin that can trap these proteases and prevent the breakdown of cartilage.
      Cytonics developed a device that use the patient's own blood to remove all cells and
      concentrate alpha-2-macroglobulin to be injected in the painful knee due to osteoarthritis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Reduction in pain after 8 weeks
time frame: 8 weeks
description: Statistically significant reduction in pain after 8 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score
measure: Reduction in pain while walking at 8 weeks
time frame: 8 weeks
description: Statistically significant reduction in pain while walking after 8 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score
measure: Reduction in pain after 2 weeks
time frame: 2 weeks
description: Statistically significant reduction in pain after 2 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score.
measure: Reduction in pain while walking at 2 weeks
time frame: 2 weeks
description: Statistically significant reduction in pain while walking after 2 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score
measure: Reduction in pain at 24 weeks
time frame: 24 weeks
description: Statistically significant reduction in pain after 24 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score
measure: Reduction in pain while walking after 24 weeks
time frame: 24 week
description: Statistically significant reduction in pain while walking after 24 weeks from initial treatment of APIC-CF compared to control as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) total score
arm group label: APIC-CF 4cc,
arm group type: Experimental
description: APIC-CF 4cc, once at first day
arm group label: APIC-CF, 2cc
arm group type: Experimental
description: APIC-CF, 2cc, one at first day
arm group label: Saline
arm group type: Placebo Comparator
intervention type: Device
intervention name: APIC-CF, 4 cc
arm group label: APIC-CF 4cc,
intervention type: Device
intervention name: APIC-CF, 2 cc
arm group label: APIC-CF, 2cc
intervention type: Other
intervention name: Placebo Comparator: Saline
description: Placebo Comparator: Saline
arm group label: Saline
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: No
last name: Gaetano Scuderi, MD
phone: 561-575-4451
phone ext: 1
email: scuderimd@aol.com
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee