<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/NCT04486963</url>
  </required_header>
  <id_info>
    <org_study_id>TSL-TCM-SHJSMW-IIa</org_study_id>
    <nct_id>NCT04486963</nct_id>
  </id_info>
  <brief_title>A Phase Ⅱ Clinical Study of Sanhuangjingshimingwan in Wet( Neovascular)Age-related Macular Degeneration(wAMD) Subjects</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled, Ranibizumab Injected, Multicenter Phase II Clinical Study on the Efficacy and Safety of Sanhuangjingshimingwan in the Wet AMD(Qi and Yin Deficiency, Phlegm-blood Stasis Syndrome )Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tasly Pharmaceutical Group Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tasly Pharmaceutical Group Co., Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is to evaluate the efficacy and safety of Sanhuangjingshimingwan in Wet AMD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is to evaluate the efficacy and safety of Sanhuangjingshimingwan,give two times a&#xD;
      day versus placebo in wAMD .The clinical phase of the study comprises a 6-months double-blind&#xD;
      treatment period, resulting in 6.5-months overall duration of the study for each patient.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 24, 2020</start_date>
  <completion_date type="Actual">November 15, 2022</completion_date>
  <primary_completion_date type="Actual">November 1, 2022</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>The average number of reinjections</measure>
    <time_frame>at week 24</time_frame>
    <description>The subject is injected with Anti-VEGF（Vascular Endothelial Growth Factor） injection once 4 weeks if needed.Compare with the average shoot number of Anti-VEGF injections in both arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The percentage of subjects in both arms receiving reinjection of Anti-VEGF injection</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>The subject is injected with Anti-VEGF injection once weeks if needed.Compare with the percentage of subjects who reinjected Anti-VEGF injections in both arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The average number of days between the second injection and baseline injection</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>The subject is injected with Anti-VEGF injection once 4 weeks if needed.Compare with the average number of days between the second injection and baseline injection in both arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in BCVA</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>The subject is tested the vision(BCVA) once 4 weeks with ETDRS visual chart.Compare every visit BCVA with baseline BCVA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The BCVA increasing &gt;5, &gt;10 and &gt; 15 letters change from baseline</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>The proportion of subjects who increased BCVA &gt;5, &gt;10 and &gt; 15 letters at each visit compared with the baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The BCVA decreasing&lt;5, &lt;10 and &lt; 15 letters change form baseline</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>The proportion of subjects who decreased BCVA &lt;5, &lt;10 and &lt;15 letters at each visit compared with the baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The BCVA decreasing≥15, ≥30 letters change form baseline</measure>
    <time_frame>at week 24</time_frame>
    <description>The proportion of subjects who decreased BCVA ≥15, ≥30 letters at 24 week compared with the baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Central Retinal Thickness (CRT)</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>Change from Baseline in CRT as measured by Optical Coherence Tomography (OCT) over the study duration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Choroidal Neovascularization (CNV) area</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>Change from Baseline in CNV area as measured by Optical Coherence Tomography Angiography(OCTA) over the study duration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in leakage area</measure>
    <time_frame>at week 24</time_frame>
    <description>Change from Baseline in leakage area as measured by Fluorescein Angiography (FA) at week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in the number of polypoid choroidal vasculopathy(PCV) and Branching vascular network(BVN) area</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>Change from Baseline in the number of PCV and BVN area as measured by Indocyanine Green Angiography(ICGA) over the study duration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in TCM(Traditional Chinese Medicine) syndrome scores</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>The title of the scale is Traditional Chinese Medicine Syndrome Scale.Compared wth baseline,the scores of changes of TCM syndrome evaluation at each visit .This scale consists of two primary symptoms: Blurred vision and Metamorphopsia,and four secondary symptoms.Four levels to measure severity of primary symptoms（0、2、4、6）and secondary symptoms（0、1、2、3） respectively. The final score has a range of 0（none）to 42（severe）.TCM syndrome effect calculated by nimodipine method.The effect of TCM syndrome from negative (worsen) to 100% (disappear).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in the effective TCM syndrome scores</measure>
    <time_frame>at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24</time_frame>
    <description>The title of the scale is Traditional Chinese Medicine Syndrome Scale.Compared wth baseline,the scores of changes of TCM syndrome evaluation at each visit .This scale consists of two primary symptoms: Blurred vision and Metamorphopsia,and four secondary symptoms.Four levels to measure severity of primary symptoms（0、2、4、6）and secondary symptoms（0、1、2、3） respectively. The final score has a range of 0（none）to 42（severe）.TCM syndrome effect calculated by nimodipine method.The effect of TCM syndrome from negative (worsen) to 100% (disappear).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Age-related Macular Degeneration</condition>
  <arm_group>
    <arm_group_label>Sanhuangjingshimingwan group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sanhuangjingshimingwan,12g/bag,1 bag,Bid.Anti VEGF injection will be injected monthly if needed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sanhuangjingshimingwan Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Sanhuangjingshimingwan placebo,12g/bag,1 bag,Bid.Anti VEGF injection will be injected monthly if needed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sanhuangjingshimingwan</intervention_name>
    <description>Sanhuangjingshimingwan,12g,Bid,6 months.Anti VEGF injection will be injected monthly if needed.</description>
    <arm_group_label>Sanhuangjingshimingwan group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sanhuangjingshimingwan Placebo</intervention_name>
    <description>Sanhuangjingshimingwan Placebo,12g,Bid,6 months.Anti VEGF injection will be injected monthly if needed.</description>
    <arm_group_label>Sanhuangjingshimingwan Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients must meet the following criteria for entry into the trail:&#xD;
&#xD;
               1. Meet the diagnostic criteria for wAMD.&#xD;
&#xD;
               2. Meet the Traditional Chinese Medicine diagnostic criteria for Qi and Yin&#xD;
                  Deficiency, Phlegm-blood Stasis Syndrome.&#xD;
&#xD;
               3. Presence of choroidal neovascularization secondary to wAMD, and/or simple eye&#xD;
                  with blood, edema, leakage, hard exudation in or below the retina, and detachment&#xD;
                  of retinal pigment epithelium or neuroepithelium epithelium.&#xD;
&#xD;
               4. 50 years≤Age≤80 years of either gender.&#xD;
&#xD;
               5. BCVA 25 - 78 ETDRS letters(0.06~0.6, inclusive).&#xD;
&#xD;
               6. Signed informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who meet any of the following criteria will be excluded from study entry:&#xD;
&#xD;
               1. Presence of pathological myopia,high myopia caused of secondary choroidal&#xD;
                  neovascularization, glaucoma, diabetic retinopathy, retinal arteriovenous&#xD;
                  obstruction, optic neuropathy (optic neuritis, atrophy, papillary edema), macular&#xD;
                  hole, acute phase of intraocular inflammation.&#xD;
&#xD;
               2. Only retinal pigment epithelium-retinal detachment.&#xD;
&#xD;
               3. The CNV area is more than 12 optic disk area (30mm2).&#xD;
&#xD;
               4. Subfoveal structural damage or fibrosis.&#xD;
&#xD;
               5. Subjects that have unclear refractive stroma(e.g.vitreous hemorrhage, cataracts)&#xD;
                  caused fundus observation difficulty or undergone vitrectomy.&#xD;
&#xD;
               6. Subjects that have presence of other causes of choroidal neovascularization.&#xD;
&#xD;
               7. Subjects that have participated in other study of treatment with study drug&#xD;
                  within the last 3 months before the screening.&#xD;
&#xD;
               8. Subjects that have treated with photodynamic therapy, external beam radiological&#xD;
                  therapy, argon laser photocoagulation in macular area, macular surgery,&#xD;
                  transpupillary thermotherapy, hormone to treat wAMD in any eye within the last 6&#xD;
                  months before the screening.&#xD;
&#xD;
               9. Subjects that have undergone previous any eye surgery(except eyelid surgery).&#xD;
&#xD;
              10. Subjects that have intravitreal anti-VEGF injections in the past 3 months.&#xD;
&#xD;
              11. Subjects with history of fundus fluorescein and indocyanine green allergy.&#xD;
&#xD;
              12. Subjects that have any contraindications in the directions of&#xD;
                  ranibizumab(LUCENTIS)injection.&#xD;
&#xD;
              13. Subjects that have had severe heart disease in the last 6 months,such as&#xD;
                  congestive heart failure，unstable angina，acute coronary syndrome，myocardial&#xD;
                  infarction，Coronary revascularization，artery thrombosis, and ventricular&#xD;
                  arrhythmia that need treatment.&#xD;
&#xD;
              14. Subjects with uncontrolled hypertension（After antihypertension treatment&#xD;
                  SBP≥140mmHg、DBP≥90mmHg）.&#xD;
&#xD;
              15. PLT≤100×109/L; Coagulation function disorders;TBIL（Total Bilirubin）&gt;1.5×UNL（Upper&#xD;
                  Limits of Normal）;ALT（Alanine Transaminase）&gt;2.5×UNL or AST（Aspartate&#xD;
                  aminotransferase）&gt;2.5×UNL;Cr（Creatinine）&gt;1.5×UNL.&#xD;
&#xD;
              16. Subjects with uncontrolled disease history, such as serious mental, neurological,&#xD;
                  respiratory, immune, blood and other system diseases, malignant tumors and that&#xD;
                  not suitable for the study per the investigator's judgment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rui Liu</last_name>
    <role>Study Director</role>
    <affiliation>Tasly Group, Co. Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Tongren Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Hospital of Hebei Medical University</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tianjin Eye Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tianjin Medical University Eye Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>wAMD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</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/NCT04486963
org study id: TSL-TCM-SHJSMW-IIa
nct id: NCT04486963
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study is to evaluate the efficacy and safety of Sanhuangjingshimingwan in Wet AMD.
The study is to evaluate the efficacy and safety of Sanhuangjingshimingwan,give two times a
      day versus placebo in wAMD .The clinical phase of the study comprises a 6-months double-blind
      treatment period, resulting in 6.5-months overall duration of the study for each patient.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The average number of reinjections
time frame: at week 24
description: The subject is injected with Anti-VEGF（Vascular Endothelial Growth Factor） injection once 4 weeks if needed.Compare with the average shoot number of Anti-VEGF injections in both arms.
measure: The percentage of subjects in both arms receiving reinjection of Anti-VEGF injection
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: The subject is injected with Anti-VEGF injection once weeks if needed.Compare with the percentage of subjects who reinjected Anti-VEGF injections in both arms.
measure: The average number of days between the second injection and baseline injection
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: The subject is injected with Anti-VEGF injection once 4 weeks if needed.Compare with the average number of days between the second injection and baseline injection in both arms.
measure: Change from baseline in BCVA
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: The subject is tested the vision(BCVA) once 4 weeks with ETDRS visual chart.Compare every visit BCVA with baseline BCVA.
measure: The BCVA increasing >5, >10 and > 15 letters change from baseline
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: The proportion of subjects who increased BCVA >5, >10 and > 15 letters at each visit compared with the baseline.
measure: The BCVA decreasing<5, <10 and < 15 letters change form baseline
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: The proportion of subjects who decreased BCVA <5, <10 and <15 letters at each visit compared with the baseline.
measure: The BCVA decreasing≥15, ≥30 letters change form baseline
time frame: at week 24
description: The proportion of subjects who decreased BCVA ≥15, ≥30 letters at 24 week compared with the baseline.
measure: Change from Baseline in Central Retinal Thickness (CRT)
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: Change from Baseline in CRT as measured by Optical Coherence Tomography (OCT) over the study duration.
measure: Change from Baseline in Choroidal Neovascularization (CNV) area
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: Change from Baseline in CNV area as measured by Optical Coherence Tomography Angiography(OCTA) over the study duration.
measure: Change from Baseline in leakage area
time frame: at week 24
description: Change from Baseline in leakage area as measured by Fluorescein Angiography (FA) at week 24.
measure: Change from Baseline in the number of polypoid choroidal vasculopathy(PCV) and Branching vascular network(BVN) area
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: Change from Baseline in the number of PCV and BVN area as measured by Indocyanine Green Angiography(ICGA) over the study duration.
measure: Change from Baseline in TCM(Traditional Chinese Medicine) syndrome scores
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: The title of the scale is Traditional Chinese Medicine Syndrome Scale.Compared wth baseline,the scores of changes of TCM syndrome evaluation at each visit .This scale consists of two primary symptoms: Blurred vision and Metamorphopsia,and four secondary symptoms.Four levels to measure severity of primary symptoms（0、2、4、6）and secondary symptoms（0、1、2、3） respectively. The final score has a range of 0（none）to 42（severe）.TCM syndrome effect calculated by nimodipine method.The effect of TCM syndrome from negative (worsen) to 100% (disappear).
measure: Change from Baseline in the effective TCM syndrome scores
time frame: at screening;at week 4;at week 8;at week 12;at week 16;at week 20;at week 24
description: The title of the scale is Traditional Chinese Medicine Syndrome Scale.Compared wth baseline,the scores of changes of TCM syndrome evaluation at each visit .This scale consists of two primary symptoms: Blurred vision and Metamorphopsia,and four secondary symptoms.Four levels to measure severity of primary symptoms（0、2、4、6）and secondary symptoms（0、1、2、3） respectively. The final score has a range of 0（none）to 42（severe）.TCM syndrome effect calculated by nimodipine method.The effect of TCM syndrome from negative (worsen) to 100% (disappear).
arm group label: Sanhuangjingshimingwan group
arm group type: Experimental
description: Sanhuangjingshimingwan,12g/bag,1 bag,Bid.Anti VEGF injection will be injected monthly if needed.
arm group label: Sanhuangjingshimingwan Placebo group
arm group type: Placebo Comparator
description: Sanhuangjingshimingwan placebo,12g/bag,1 bag,Bid.Anti VEGF injection will be injected monthly if needed.
intervention type: Drug
intervention name: Sanhuangjingshimingwan
description: Sanhuangjingshimingwan,12g,Bid,6 months.Anti VEGF injection will be injected monthly if needed.
arm group label: Sanhuangjingshimingwan group
intervention type: Drug
intervention name: Sanhuangjingshimingwan Placebo
description: Sanhuangjingshimingwan Placebo,12g,Bid,6 months.Anti VEGF injection will be injected monthly if needed.
arm group label: Sanhuangjingshimingwan Placebo group
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Rui Liu
role: Study Director
affiliation: Tasly Group, Co. Ltd.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Macular Degeneration