<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/NCT01689337</url>
  </required_header>
  <id_info>
    <org_study_id>EMR700692-007</org_study_id>
    <secondary_id>2012-001431-31</secondary_id>
    <nct_id>NCT01689337</nct_id>
  </id_info>
  <brief_title>A Multicenter Trial of Sprifermin (AS902330 [Recombinant Human Fibroblast Growth Factor-18]) or Placebo After Microfracture Surgery for Cartilage Injury of the Knee</brief_title>
  <official_title>A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase II Trial to Investigate the Efficacy and Safety of 30 mcg and 100 mcg AS902330 Given as One Cycle of Three Intra-articular Knee Injections Once a Week for Three Weeks as an Adjunct Treatment to Patients Following Microfracture Surgery for Cartilage Injury of the Knee.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>EMD Serono</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>EMD Serono</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2, double-blind, multicenter, randomized, placebo-controlled trial to&#xD;
      evaluate the efficacy and safety of Sprifermin (AS902330) (recombinant human fibroblast&#xD;
      growth factor-18 [rhFGF-18]) as an adjunct treatment to subjects following microfracture&#xD;
      (MFx) surgery for cartilage injury of the knee.&#xD;
&#xD;
      Primary Objectives&#xD;
&#xD;
        -  To evaluate the effect of Sprifermin (AS902330) intra-articular knee injections as&#xD;
           adjunct to microfracture (MFx) surgery on the composition of the refilled cartilage in&#xD;
           the target knee, as measured by gadolinium-enhanced magnetic resonance imaging (MRI) of&#xD;
           cartilage (dGEMRIC) time constant 1 (T1) relaxation time at 6 months after MFx surgery&#xD;
&#xD;
        -  To evaluate the safety profile of Sprifermin (AS902330) when administered&#xD;
           intra-articular into the knee as adjunct to MFx surgery in subjects with cartilage&#xD;
           injury of the knee&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
        -  To further support the efficacy and safety of Sprifermin (AS902330) as an adjunct to MFx&#xD;
           for cartilage injury repair through symptomatic outcomes and quantitative MRI&#xD;
           measurement&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was discontinued due to low recruitment.&#xD;
  </why_stopped>
  <start_date>April 2013</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</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>Composition of the Refilled Cartilage Measured by Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) Using T1 Relaxation Time at Month 6 Post-MFx Surgery</measure>
    <time_frame>6 months post-MFx surgery</time_frame>
    <description>The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composition of the Refilled Cartilage Measured by dGEMRIC Using T1 Relaxation Time Beyond Month 6 Post-MFx Surgery</measure>
    <time_frame>Every 6 months up to 5 years beyond 6 months post-MFx surgery</time_frame>
    <description>The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Participant-reported Outcome Measure: Knee Injury and Osteoarthritis Outcome Score (KOOS) Sub-scores for Pain and Activities of Daily Living (ADL)</measure>
    <time_frame>Every 6 months up to 5 years</time_frame>
    <description>The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, function in sport and recreation (FSR), and impact on quality of life (QOL) (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in pain and ADL sub-scores was to be calculated by the respective scores at the specific time point minus the scores at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Participant-reported Outcome Measure: Total KOOS Score, Three KOOS Sub-scores and Total KOOS Minus FSR Sub-score</measure>
    <time_frame>Every 6 months up to 5 years</time_frame>
    <description>The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, FSR, and impact on QOL (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in total KOOS score; other symptoms, knee-related QOL, and FSR sub-scores; and total KOOS minus FSR sub-score was to be calculated by the respective scores at the specific time point minus the scores at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Participant-reported Outcome Measure: Numeric Rating Scale (NRS) Score</measure>
    <time_frame>Every 6 months up to 5 years</time_frame>
    <description>Knee pain was to be rated by the participant using an 11-point NRS of pain intensity. The NRS is scaled from 0 (no pain) to 10 (worst possible pain). Change from baseline in NRS score was to be calculated by the score at the specific time point minus the score at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Participant-reported Outcome Measure: Lower Extremity Activity Scale (LEAS) Score</measure>
    <time_frame>Every 6 months up to 5 years</time_frame>
    <description>The LEAS is an 18-level single-question self-administered scale that has been validated as a clinical outcome measure for the assessment of participants' actual activity levels. The LEAS is scaled from 1 to 18, with 18 indicating levels of highest activity. Change from baseline in LEAS score was to be calculated by the score at the specific time point minus the score at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Physician-reported Outcome Measure: Lysholm Knee Scale Score</measure>
    <time_frame>Every 6 months up to 5 years</time_frame>
    <description>The Lysholm knee scale is a physician-reported outcome measure to assess knee function after ligament injury. It is scaled from 0 to 100 with higher scores representing better function. Change from baseline in Lysholm knee scale score was to be calculated by the score at the specific time point minus the score at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composition of the Refilled Cartilage Using T2 Mapping</measure>
    <time_frame>Every 6 months up to 5 years</time_frame>
    <description>The transverse relaxation time T2 mapping is an MRI technique that is able to evaluate collagen organization and orientation within cartilage. Composition of the refilled cartilage was to be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of the Refilled Cartilage</measure>
    <time_frame>Every 6 months up to 5 years</time_frame>
    <description>Volume of the refilled cartilage was to be measured by MRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score</measure>
    <time_frame>Every 6 months up to 5 years</time_frame>
    <description>The MOCART score is used to describe the constitution of the cartilage repair tissue and the surrounding structures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Six-minute Walk Test</measure>
    <time_frame>Every 3 months up to 5 years beyond Month 6 post-MFx surgery</time_frame>
    <description>Six (6)-minute walk test is used to measure gait function and for pre- and post-operative evaluation in cartilage injury repair. Maximum comfortable distance (in meters) that a participant can walk in 6 minutes was to be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Baseline up to Month 60</time_frame>
    <description>An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE is an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Cartilage Injury of Knee</condition>
  <arm_group>
    <arm_group_label>Sprifermin (AS902330), 30 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Sprifermin (AS902330), 100 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sprifermin (AS902330)</intervention_name>
    <description>Sprifermin (AS902330) will be administered at a dose of 30 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
    <arm_group_label>Sprifermin (AS902330), 30 mcg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sprifermin (AS902330)</intervention_name>
    <description>Sprifermin (AS902330) will be administered at a dose of 100 mcg as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
    <arm_group_label>Sprifermin (AS902330), 100 mcg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo matched to Sprifermin (AS902330) will be administered as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with candidature for MFx surgery on the femoral articular surfaces (medial or&#xD;
             lateral condyles or trochlear groove), with intact subchondral bone&#xD;
&#xD;
          -  Subjects with moderate to severe pain in the target knee prior to surgery; average&#xD;
             score greater than equal to (&gt;=) 4.0 over 7 consecutive days on numeric rating scale&#xD;
             of pain intensity (completed within 30 [+15] days before surgery)&#xD;
&#xD;
          -  Intraoperative inclusion criteria: Subjects with 1 or 2 focal chondral lesions per&#xD;
             target knee, where peripheral debridement to healthy cartilage results in all of the&#xD;
             following:&#xD;
&#xD;
               -  Each lesion has an area of &gt;= 1 square centimeter (cm^2) and less than equal to&#xD;
                  (&lt;=) 4 cm^2&#xD;
&#xD;
               -  Each lesion is &lt;= 6 millimeter (mm) in depth, as measured from the surrounding&#xD;
                  subchondral plate&#xD;
&#xD;
               -  Arthroscopic confirmation that each non-osteochondritis dissecans (OCD) lesion is&#xD;
                  between International Cartilage Repair Society (ICRS) Grades I and III (D); a&#xD;
                  Grade III non-OCD lesion is equivalent to an Outerbridge Grade IV lesion with&#xD;
                  minimal subchondral bone loss&#xD;
&#xD;
          -  Other protocol-defined inclusion criteria could apply&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with prior marrow stimulation treatment of the target knee, that is, MFx,&#xD;
             micro-drilling, abrasion chondroplasty or cartilage repair including, but not limited&#xD;
             to, autologous chondrocyte implantation (ACI), matrix/membrane autologous chondrocyte&#xD;
             implantation (MACI), or osteochondral transplantation (autologous or allogeneic)&#xD;
&#xD;
          -  Subjects with body mass index (BMI) of greater than 35 kilogram per square meter&#xD;
             (kg/m^2) at screening&#xD;
&#xD;
          -  Malalignment of the target knee greater than 5 degrees as measured from the mechanical&#xD;
             axis, as confirmed by alignment (long bone) X-ray images&#xD;
&#xD;
          -  Subjects with clinical and/or radiographic disease diagnosis of the target knee joint&#xD;
             including, but not limited to the following: generalized osteoarthritis (OA),&#xD;
             rheumatoid arthritis, or avascular necrosis&#xD;
&#xD;
          -  Subjects who have any contraindication to MRI or gadolinium-based or iodinated&#xD;
             contrast agents according to the site's standard practice guidelines&#xD;
&#xD;
          -  Other protocol-defined exclusion criteria could apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <removed_countries>
    <country>Germany</country>
    <country>United States</country>
  </removed_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>July 8, 2015</results_first_submitted>
  <results_first_submitted_qc>August 14, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 31, 2015</results_first_posted>
  <last_update_submitted>January 12, 2017</last_update_submitted>
  <last_update_submitted_qc>January 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Microfracture surgery</keyword>
  <keyword>Cartilage repair</keyword>
  <keyword>Knee surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Wounds and Injuries</mesh_term>
    <mesh_term>Fractures, Stress</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Sprifermin (AS902330) 30 microgram (mcg) and placebo arms were planned, but did not enroll participants due to early study discontinuation.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Sprifermin (AS902330), 100 mcg</title>
          <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after microfracture (MFx) surgery.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study Discontinuation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intention-to-treat (ITT) analysis set included all participants randomly allocated to treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Sprifermin (AS902330), 100 mcg</title>
          <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after microfracture (MFx) surgery.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Composition of the Refilled Cartilage Measured by Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) Using T1 Relaxation Time at Month 6 Post-MFx Surgery</title>
        <description>The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.</description>
        <time_frame>6 months post-MFx surgery</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Composition of the Refilled Cartilage Measured by Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) Using T1 Relaxation Time at Month 6 Post-MFx Surgery</title>
          <description>The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composition of the Refilled Cartilage Measured by dGEMRIC Using T1 Relaxation Time Beyond Month 6 Post-MFx Surgery</title>
        <description>The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.</description>
        <time_frame>Every 6 months up to 5 years beyond 6 months post-MFx surgery</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Composition of the Refilled Cartilage Measured by dGEMRIC Using T1 Relaxation Time Beyond Month 6 Post-MFx Surgery</title>
          <description>The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Participant-reported Outcome Measure: Knee Injury and Osteoarthritis Outcome Score (KOOS) Sub-scores for Pain and Activities of Daily Living (ADL)</title>
        <description>The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, function in sport and recreation (FSR), and impact on quality of life (QOL) (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in pain and ADL sub-scores was to be calculated by the respective scores at the specific time point minus the scores at baseline.</description>
        <time_frame>Every 6 months up to 5 years</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after microfracture (MFx) surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Participant-reported Outcome Measure: Knee Injury and Osteoarthritis Outcome Score (KOOS) Sub-scores for Pain and Activities of Daily Living (ADL)</title>
          <description>The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, function in sport and recreation (FSR), and impact on quality of life (QOL) (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in pain and ADL sub-scores was to be calculated by the respective scores at the specific time point minus the scores at baseline.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Participant-reported Outcome Measure: Total KOOS Score, Three KOOS Sub-scores and Total KOOS Minus FSR Sub-score</title>
        <description>The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, FSR, and impact on QOL (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in total KOOS score; other symptoms, knee-related QOL, and FSR sub-scores; and total KOOS minus FSR sub-score was to be calculated by the respective scores at the specific time point minus the scores at baseline.</description>
        <time_frame>Every 6 months up to 5 years</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Participant-reported Outcome Measure: Total KOOS Score, Three KOOS Sub-scores and Total KOOS Minus FSR Sub-score</title>
          <description>The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, FSR, and impact on QOL (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in total KOOS score; other symptoms, knee-related QOL, and FSR sub-scores; and total KOOS minus FSR sub-score was to be calculated by the respective scores at the specific time point minus the scores at baseline.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Participant-reported Outcome Measure: Numeric Rating Scale (NRS) Score</title>
        <description>Knee pain was to be rated by the participant using an 11-point NRS of pain intensity. The NRS is scaled from 0 (no pain) to 10 (worst possible pain). Change from baseline in NRS score was to be calculated by the score at the specific time point minus the score at baseline.</description>
        <time_frame>Every 6 months up to 5 years</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after microfracture (MFx) surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Participant-reported Outcome Measure: Numeric Rating Scale (NRS) Score</title>
          <description>Knee pain was to be rated by the participant using an 11-point NRS of pain intensity. The NRS is scaled from 0 (no pain) to 10 (worst possible pain). Change from baseline in NRS score was to be calculated by the score at the specific time point minus the score at baseline.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Participant-reported Outcome Measure: Lower Extremity Activity Scale (LEAS) Score</title>
        <description>The LEAS is an 18-level single-question self-administered scale that has been validated as a clinical outcome measure for the assessment of participants' actual activity levels. The LEAS is scaled from 1 to 18, with 18 indicating levels of highest activity. Change from baseline in LEAS score was to be calculated by the score at the specific time point minus the score at baseline.</description>
        <time_frame>Every 6 months up to 5 years</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>AS902330, 100 mcg</title>
            <description>AS902330 was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Participant-reported Outcome Measure: Lower Extremity Activity Scale (LEAS) Score</title>
          <description>The LEAS is an 18-level single-question self-administered scale that has been validated as a clinical outcome measure for the assessment of participants' actual activity levels. The LEAS is scaled from 1 to 18, with 18 indicating levels of highest activity. Change from baseline in LEAS score was to be calculated by the score at the specific time point minus the score at baseline.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Physician-reported Outcome Measure: Lysholm Knee Scale Score</title>
        <description>The Lysholm knee scale is a physician-reported outcome measure to assess knee function after ligament injury. It is scaled from 0 to 100 with higher scores representing better function. Change from baseline in Lysholm knee scale score was to be calculated by the score at the specific time point minus the score at baseline.</description>
        <time_frame>Every 6 months up to 5 years</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Physician-reported Outcome Measure: Lysholm Knee Scale Score</title>
          <description>The Lysholm knee scale is a physician-reported outcome measure to assess knee function after ligament injury. It is scaled from 0 to 100 with higher scores representing better function. Change from baseline in Lysholm knee scale score was to be calculated by the score at the specific time point minus the score at baseline.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composition of the Refilled Cartilage Using T2 Mapping</title>
        <description>The transverse relaxation time T2 mapping is an MRI technique that is able to evaluate collagen organization and orientation within cartilage. Composition of the refilled cartilage was to be reported.</description>
        <time_frame>Every 6 months up to 5 years</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Composition of the Refilled Cartilage Using T2 Mapping</title>
          <description>The transverse relaxation time T2 mapping is an MRI technique that is able to evaluate collagen organization and orientation within cartilage. Composition of the refilled cartilage was to be reported.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Volume of the Refilled Cartilage</title>
        <description>Volume of the refilled cartilage was to be measured by MRI.</description>
        <time_frame>Every 6 months up to 5 years</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of the Refilled Cartilage</title>
          <description>Volume of the refilled cartilage was to be measured by MRI.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score</title>
        <description>The MOCART score is used to describe the constitution of the cartilage repair tissue and the surrounding structures.</description>
        <time_frame>Every 6 months up to 5 years</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score</title>
          <description>The MOCART score is used to describe the constitution of the cartilage repair tissue and the surrounding structures.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Six-minute Walk Test</title>
        <description>Six (6)-minute walk test is used to measure gait function and for pre- and post-operative evaluation in cartilage injury repair. Maximum comfortable distance (in meters) that a participant can walk in 6 minutes was to be reported.</description>
        <time_frame>Every 3 months up to 5 years beyond Month 6 post-MFx surgery</time_frame>
        <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Six-minute Walk Test</title>
          <description>Six (6)-minute walk test is used to measure gait function and for pre- and post-operative evaluation in cartilage injury repair. Maximum comfortable distance (in meters) that a participant can walk in 6 minutes was to be reported.</description>
          <population>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
        <description>An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE is an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.</description>
        <time_frame>Baseline up to Month 60</time_frame>
        <population>The safety analysis set included all participants who received at least 1 dose of trial drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Sprifermin (AS902330), 100 mcg</title>
            <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
          <description>An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE is an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.</description>
          <population>The safety analysis set included all participants who received at least 1 dose of trial drug.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 6 months</time_frame>
      <desc>An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Sprifermin (AS902330), 100 mcg</title>
          <description>Sprifermin (AS902330) was administered at a dose of 100 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after microfracture (MFx) surgery.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA Version 16.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Streptococcal pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Knee swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Panic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor can with reasonable grounds require changes to the communication which do not change the scientific statement or neutrality of the communication.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Merck KGaA Communication Center</name_or_title>
      <organization>Merck Serono, a division of Merck KGaA</organization>
      <phone>+49-6151-72-5200</phone>
      <email>service@merckgroup.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01689337
org study id: EMR700692-007
secondary id: 2012-001431-31
nct id: NCT01689337
lead sponsor: 
has dmc: No
This is a Phase 2, double-blind, multicenter, randomized, placebo-controlled trial to
      evaluate the efficacy and safety of Sprifermin (AS902330) (recombinant human fibroblast
      growth factor-18 [rhFGF-18]) as an adjunct treatment to subjects following microfracture
      (MFx) surgery for cartilage injury of the knee.

      Primary Objectives

        -  To evaluate the effect of Sprifermin (AS902330) intra-articular knee injections as
           adjunct to microfracture (MFx) surgery on the composition of the refilled cartilage in
           the target knee, as measured by gadolinium-enhanced magnetic resonance imaging (MRI) of
           cartilage (dGEMRIC) time constant 1 (T1) relaxation time at 6 months after MFx surgery

        -  To evaluate the safety profile of Sprifermin (AS902330) when administered
           intra-articular into the knee as adjunct to MFx surgery in subjects with cartilage
           injury of the knee

      Secondary Objectives

        -  To further support the efficacy and safety of Sprifermin (AS902330) as an adjunct to MFx
           for cartilage injury repair through symptomatic outcomes and quantitative MRI
           measurement
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Composition of the Refilled Cartilage Measured by Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) Using T1 Relaxation Time at Month 6 Post-MFx Surgery
time frame: 6 months post-MFx surgery
description: The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.
measure: Composition of the Refilled Cartilage Measured by dGEMRIC Using T1 Relaxation Time Beyond Month 6 Post-MFx Surgery
time frame: Every 6 months up to 5 years beyond 6 months post-MFx surgery
description: The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.
measure: Change From Baseline in Participant-reported Outcome Measure: Knee Injury and Osteoarthritis Outcome Score (KOOS) Sub-scores for Pain and Activities of Daily Living (ADL)
time frame: Every 6 months up to 5 years
description: The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, function in sport and recreation (FSR), and impact on quality of life (QOL) (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in pain and ADL sub-scores was to be calculated by the respective scores at the specific time point minus the scores at baseline.
measure: Change From Baseline in Participant-reported Outcome Measure: Total KOOS Score, Three KOOS Sub-scores and Total KOOS Minus FSR Sub-score
time frame: Every 6 months up to 5 years
description: The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, FSR, and impact on QOL (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in total KOOS score; other symptoms, knee-related QOL, and FSR sub-scores; and total KOOS minus FSR sub-score was to be calculated by the respective scores at the specific time point minus the scores at baseline.
measure: Change From Baseline in Participant-reported Outcome Measure: Numeric Rating Scale (NRS) Score
time frame: Every 6 months up to 5 years
description: Knee pain was to be rated by the participant using an 11-point NRS of pain intensity. The NRS is scaled from 0 (no pain) to 10 (worst possible pain). Change from baseline in NRS score was to be calculated by the score at the specific time point minus the score at baseline.
measure: Change From Baseline in Participant-reported Outcome Measure: Lower Extremity Activity Scale (LEAS) Score
time frame: Every 6 months up to 5 years
description: The LEAS is an 18-level single-question self-administered scale that has been validated as a clinical outcome measure for the assessment of participants' actual activity levels. The LEAS is scaled from 1 to 18, with 18 indicating levels of highest activity. Change from baseline in LEAS score was to be calculated by the score at the specific time point minus the score at baseline.
measure: Change From Baseline in the Physician-reported Outcome Measure: Lysholm Knee Scale Score
time frame: Every 6 months up to 5 years
description: The Lysholm knee scale is a physician-reported outcome measure to assess knee function after ligament injury. It is scaled from 0 to 100 with higher scores representing better function. Change from baseline in Lysholm knee scale score was to be calculated by the score at the specific time point minus the score at baseline.
measure: Composition of the Refilled Cartilage Using T2 Mapping
time frame: Every 6 months up to 5 years
description: The transverse relaxation time T2 mapping is an MRI technique that is able to evaluate collagen organization and orientation within cartilage. Composition of the refilled cartilage was to be reported.
measure: Volume of the Refilled Cartilage
time frame: Every 6 months up to 5 years
description: Volume of the refilled cartilage was to be measured by MRI.
measure: Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score
time frame: Every 6 months up to 5 years
description: The MOCART score is used to describe the constitution of the cartilage repair tissue and the surrounding structures.
measure: Six-minute Walk Test
time frame: Every 3 months up to 5 years beyond Month 6 post-MFx surgery
description: Six (6)-minute walk test is used to measure gait function and for pre- and post-operative evaluation in cartilage injury repair. Maximum comfortable distance (in meters) that a participant can walk in 6 minutes was to be reported.
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Baseline up to Month 60
description: An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE is an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
arm group label: Sprifermin (AS902330), 30 mcg
arm group type: Experimental
arm group label: Sprifermin (AS902330), 100 mcg
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Sprifermin (AS902330)
description: Sprifermin (AS902330) will be administered at a dose of 30 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.
arm group label: Sprifermin (AS902330), 30 mcg
intervention type: Drug
intervention name: Sprifermin (AS902330)
description: Sprifermin (AS902330) will be administered at a dose of 100 mcg as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.
arm group label: Sprifermin (AS902330), 100 mcg
intervention type: Drug
intervention name: Placebo
description: Placebo matched to Sprifermin (AS902330) will be administered as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Medical Responsible
role: Study Director
affiliation: EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
country: Germany
country: United States
responsible party type: Sponsor
mesh term: Wounds and Injuries
mesh term: Fractures, Stress
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Efficacy analysis was not performed as only one participant was enrolled in the study. The study was terminated due to low recruitment.
point of contact: 