<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/NCT03838666</url>
  </required_header>
  <id_info>
    <org_study_id>AMSC-RC-001</org_study_id>
    <nct_id>NCT03838666</nct_id>
  </id_info>
  <brief_title>Utilization of AMSC to Enhance Rotator Cuff Repair - Safety and Efficacy</brief_title>
  <acronym>AMSC-RC-001</acronym>
  <official_title>Utilization of Autologous Mesenchymal Cells to Enhance Rotator Cuff Repair - a Prospective Non-randomized, Open-Label Study to Assess the Safety and the Efficacy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bioinova, s.r.o.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Department of Neurology, University Hospital Motol, Prague, Czech Republic</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bioinova, s.r.o.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Subjects received perioperative hAMSC treatment in order to accelerate the healing of the&#xD;
      surgically repaired rotator cuff and increase the mechanical properties of the tendon,&#xD;
      according to inclusion and exclusion criteria (see below). Each patient will undergo&#xD;
      post-operative follow-up at 6 weeks, 6 months and 12 months after the surgery. This will&#xD;
      include a visual analogue score for pain (VAS), a questionnaire for the subjective Constant&#xD;
      shoulder score, and the subjective questions of the University of California (UCLA) score.&#xD;
      Preoperative and postoperative MRI at 12 months will be done to evaluate the quality of the&#xD;
      rotator cuff repair.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients will undergo an arthroscopic rotator cuff repair augmented by mesenchymal&#xD;
      stem cells (MSCs). The primary objective of the trial is to assess the safety and&#xD;
      tolerability of autologous mesenchymal stem cells treatment applied during arthroscopic&#xD;
      rotator cuff repair.&#xD;
&#xD;
      The condition of the patient will be monitored throughout the study. At each visit, adverse&#xD;
      events (AEs) will be elicited using a standard non-leading questions. In addition, any signs&#xD;
      or symptoms will be observed. All AEs will be collected as:&#xD;
&#xD;
        -  patient's positive response to questions about their health&#xD;
&#xD;
        -  symptoms spontaneously reported by the patient&#xD;
&#xD;
        -  clinically relevant changes and abnormalities observed by the Investigator (e.g. local&#xD;
           and systemic tolerability, clinically significant laboratory measurements confirmed by&#xD;
           repeated measurement, results of physical examinations).&#xD;
&#xD;
      Clinical improvement will be measured by clinical outcome scores (Constant shoulder score and&#xD;
      UCLA Shoulder rating scale) at 6 weeks, 6 months and 1 year after the surgery. MRI (Magnetic&#xD;
      Resonance Imaging) findings made preoperatively and at 12 months (1 year) after operation&#xD;
      will be evaluated.&#xD;
&#xD;
      During the indication visit, patient's history will be taken and preoperative MRI evaluated.&#xD;
      Written consent form will be collected from the patient after detailed education of the&#xD;
      patient by the investigator.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Primary endpoint (safety) has been achieved&#xD;
  </why_stopped>
  <start_date type="Actual">December 12, 2012</start_date>
  <completion_date type="Actual">November 18, 2015</completion_date>
  <primary_completion_date type="Actual">November 18, 2015</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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety: To assess the occurrence of adverse events of treatment by hAMSC - systemic reactions.</measure>
    <time_frame>1 year</time_frame>
    <description>Safety and tolerability of hAMSC treatment applied during the surgical rotator cuff repair will be recorded - systemic reactions including allergic reaction or sepsis at Visits I through VI.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety: To assess the occurrence of adverse events of treatment by autologous mesenchymal stem cells - local reactions.</measure>
    <time_frame>1 year</time_frame>
    <description>Safety and tolerability of autologous mesenchymal stem cells treatment applied during the surgical rotator cuff repair will be recorded - local reactions including pain, bleeding, local infection at Visits I through VI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - Visual Analogue Score (VAS)</measure>
    <time_frame>1 year</time_frame>
    <description>The efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function measured by changes in Visual Analogue Score (VAS) (meter-shaped scale; in mm) at Visits II, IV, V, and VI.&#xD;
VAS is a self-report measure consisting simply of a 10 centimeter line with a statement at each end representing one extreme of the dimension being measured (most often intensity of pain). The respondent gives their indication with a pen mark on the line corresponding to their answer, e.g. the present pain level.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - Constant Shoulder Score</measure>
    <time_frame>1 year</time_frame>
    <description>The secondary efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function by changes in Constant Shoulder Score (points) at Visits II, IV, V, and VI.&#xD;
Measurements: Pain, Activities of daily living, Range of movement (forward flexion, abduction, external rotation, internal rotation), Power.&#xD;
Less points (out of 100) means more severe condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - UCLA Shoulder Rating Score</measure>
    <time_frame>1 year</time_frame>
    <description>The secondary efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function by changes in UCLA Shoulder Rating Score (points) at Visits II, IV, V, and VI.&#xD;
Measurements: Pain, Function, Active forward flexion, Strength of forward flexion (manual muscle-testing), Satisfaction of patient.&#xD;
Less points (out of 35) means more severe condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - MRI imaging - Continuation / discontinuation of the rotator cuff</measure>
    <time_frame>1 year</time_frame>
    <description>The secondary efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function which measured by MRI imaging (preoperative and at Visit VI) to evaluate the quality of the rotator cuff repair.&#xD;
Following finding will be recorded:&#xD;
Continuation / discontinuation of the rotator cuff&#xD;
preoperatively - confirmation of complete unilateral rotator cuff tear&#xD;
1 year after the treatment (Visit VI) - the quality and extent of rotator cuff repair - no recovery/partial recovery/full recovery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - MRI imaging - Fatty degeneration</measure>
    <time_frame>1 year</time_frame>
    <description>The secondary efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function which measured by MRI imaging (preoperative and at Visit VI) to evaluate the quality of the rotator cuff repair.&#xD;
Following finding will be recorded:&#xD;
- Amount of fatty degeneration - percentage of fatty infiltration of the cross sectional area of supraspinatus or infraspinatus assessed on the most lateral image on which the scapular spine is in contact with the scapular body,</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Rotator Cuff Tear</condition>
  <arm_group>
    <arm_group_label>Suspension of human autologous MSC 3P</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive perioperative hAMSC (1.5 ml) treatment in order to accelerate the healing of the surgically repaired rotator cuff and increase the mechanical properties of the tendon.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Suspension of human autologous MSC 3P</intervention_name>
    <description>Single administration of the suspension of human autologous MSC 3P in 1.5 ml on the surface of the repaired rotator cuff tendon</description>
    <arm_group_label>Suspension of human autologous MSC 3P</arm_group_label>
    <other_name>hAMSC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. males or females between 40 and 65 years of age,&#xD;
&#xD;
          2. written informed consent obtained,&#xD;
&#xD;
          3. complete unilateral rotator cuff tear on pre-operative clinical and imaging findings,&#xD;
&#xD;
          4. elected to undergo an arthroscopic repair of their rotator cuff tear,&#xD;
&#xD;
          5. agreed to wear a dedicated brace for four weeks post-operatively,&#xD;
&#xD;
          6. minimum pre-operative hemoglobin of 11.0 g/dl or more&#xD;
&#xD;
          7. pre-operative platelet count greater than 150 000 / 1 mm3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. a tear involving the subscapularis or biceps tendons,&#xD;
&#xD;
          2. a previous rotator cuff repair,&#xD;
&#xD;
          3. moderate-to-severe osteoarthritis of the glenohumeral joint,&#xD;
&#xD;
          4. loss of passive elevation in any direction when compared to the contralateral&#xD;
             shoulder,&#xD;
&#xD;
          5. fatty infiltration greater than 50 % of the cross-sectional area of supraspinatus or&#xD;
             infraspinatus assessed on the most lateral image on which the scapular spine is in&#xD;
             contact with the scapular body,&#xD;
&#xD;
          6. a massive tear with a contracted immobile cuff confirmed in operation,&#xD;
&#xD;
          7. an active infection, osteomyelitis or sepsis or distant infections which may spread to&#xD;
             the site of operation,&#xD;
&#xD;
          8. other diseases which may have limit follow-up (immunocompromising, hepatitis, active&#xD;
             tuberculosis, neoplastic diseases, septic arthritis),&#xD;
&#xD;
          9. osteomalacia or other metabolic bone disorders which may impair bone or soft tissue&#xD;
             function,&#xD;
&#xD;
         10. vascular insufficiency, muscular atrophy or neuromuscular diseases of the affected&#xD;
             arm,&#xD;
&#xD;
         11. haemato/oncological diseases,&#xD;
&#xD;
         12. pregnant or lactating women,&#xD;
&#xD;
         13. alcohol or drug abusers,&#xD;
&#xD;
         14. patients on corticosteroids, immunosuppressants or anticoagulant therapy,&#xD;
&#xD;
         15. women of childbearing potential not using effective contraception (established oral&#xD;
             contraception, intrauterine device, ligation of the uterine tube) including proven&#xD;
             contraceptive measures taken by their sexual partners,&#xD;
&#xD;
         16. fertile men not using proven contraceptive measures including effective contraception&#xD;
             of their partners (established oral contraception, intrauterine device, ligation of&#xD;
             the uterine tube).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Petr Lesny, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Bioinova, s.r.o.</affiliation>
  </overall_official>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>February 12, 2019</last_update_submitted>
  <last_update_submitted_qc>February 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</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>Rotator Cuff Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The data has been published</ipd_description>
  </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/NCT03838666
org study id: AMSC-RC-001
nct id: NCT03838666
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Subjects received perioperative hAMSC treatment in order to accelerate the healing of the
      surgically repaired rotator cuff and increase the mechanical properties of the tendon,
      according to inclusion and exclusion criteria (see below). Each patient will undergo
      post-operative follow-up at 6 weeks, 6 months and 12 months after the surgery. This will
      include a visual analogue score for pain (VAS), a questionnaire for the subjective Constant
      shoulder score, and the subjective questions of the University of California (UCLA) score.
      Preoperative and postoperative MRI at 12 months will be done to evaluate the quality of the
      rotator cuff repair.
Eligible patients will undergo an arthroscopic rotator cuff repair augmented by mesenchymal
      stem cells (MSCs). The primary objective of the trial is to assess the safety and
      tolerability of autologous mesenchymal stem cells treatment applied during arthroscopic
      rotator cuff repair.

      The condition of the patient will be monitored throughout the study. At each visit, adverse
      events (AEs) will be elicited using a standard non-leading questions. In addition, any signs
      or symptoms will be observed. All AEs will be collected as:

        -  patient's positive response to questions about their health

        -  symptoms spontaneously reported by the patient

        -  clinically relevant changes and abnormalities observed by the Investigator (e.g. local
           and systemic tolerability, clinically significant laboratory measurements confirmed by
           repeated measurement, results of physical examinations).

      Clinical improvement will be measured by clinical outcome scores (Constant shoulder score and
      UCLA Shoulder rating scale) at 6 weeks, 6 months and 1 year after the surgery. MRI (Magnetic
      Resonance Imaging) findings made preoperatively and at 12 months (1 year) after operation
      will be evaluated.

      During the indication visit, patient's history will be taken and preoperative MRI evaluated.
      Written consent form will be collected from the patient after detailed education of the
      patient by the investigator.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: To assess the occurrence of adverse events of treatment by hAMSC - systemic reactions.
time frame: 1 year
description: Safety and tolerability of hAMSC treatment applied during the surgical rotator cuff repair will be recorded - systemic reactions including allergic reaction or sepsis at Visits I through VI.
measure: Safety: To assess the occurrence of adverse events of treatment by autologous mesenchymal stem cells - local reactions.
time frame: 1 year
description: Safety and tolerability of autologous mesenchymal stem cells treatment applied during the surgical rotator cuff repair will be recorded - local reactions including pain, bleeding, local infection at Visits I through VI.
measure: Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - Visual Analogue Score (VAS)
time frame: 1 year
description: The efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function measured by changes in Visual Analogue Score (VAS) (meter-shaped scale; in mm) at Visits II, IV, V, and VI.
VAS is a self-report measure consisting simply of a 10 centimeter line with a statement at each end representing one extreme of the dimension being measured (most often intensity of pain). The respondent gives their indication with a pen mark on the line corresponding to their answer, e.g. the present pain level.
measure: Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - Constant Shoulder Score
time frame: 1 year
description: The secondary efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function by changes in Constant Shoulder Score (points) at Visits II, IV, V, and VI.
Measurements: Pain, Activities of daily living, Range of movement (forward flexion, abduction, external rotation, internal rotation), Power.
Less points (out of 100) means more severe condition.
measure: Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - UCLA Shoulder Rating Score
time frame: 1 year
description: The secondary efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function by changes in UCLA Shoulder Rating Score (points) at Visits II, IV, V, and VI.
Measurements: Pain, Function, Active forward flexion, Strength of forward flexion (manual muscle-testing), Satisfaction of patient.
Less points (out of 35) means more severe condition.
measure: Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - MRI imaging - Continuation / discontinuation of the rotator cuff
time frame: 1 year
description: The secondary efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function which measured by MRI imaging (preoperative and at Visit VI) to evaluate the quality of the rotator cuff repair.
Following finding will be recorded:
Continuation / discontinuation of the rotator cuff
preoperatively - confirmation of complete unilateral rotator cuff tear
1 year after the treatment (Visit VI) - the quality and extent of rotator cuff repair - no recovery/partial recovery/full recovery
measure: Efficacy: To evaluate the effect of hAMSCs applied during arthroscopic rotator cuff repair - MRI imaging - Fatty degeneration
time frame: 1 year
description: The secondary efficacy analysis will be evaluated by comparing pre- and post-treatment rotator cuff function which measured by MRI imaging (preoperative and at Visit VI) to evaluate the quality of the rotator cuff repair.
Following finding will be recorded:
- Amount of fatty degeneration - percentage of fatty infiltration of the cross sectional area of supraspinatus or infraspinatus assessed on the most lateral image on which the scapular spine is in contact with the scapular body,
arm group label: Suspension of human autologous MSC 3P
arm group type: Experimental
description: Patients will receive perioperative hAMSC (1.5 ml) treatment in order to accelerate the healing of the surgically repaired rotator cuff and increase the mechanical properties of the tendon.
intervention type: Drug
intervention name: Suspension of human autologous MSC 3P
description: Single administration of the suspension of human autologous MSC 3P in 1.5 ml on the surface of the repaired rotator cuff tendon
arm group label: Suspension of human autologous MSC 3P
other name: hAMSC
criteria: 
gender: All
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: No
last name: Petr Lesny, MD
role: Study Chair
affiliation: Bioinova, s.r.o.
responsible party type: Sponsor
mesh term: Rotator Cuff Injuries
sharing ipd: No
ipd description: The data has been published