<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/NCT03777254</url>
  </required_header>
  <id_info>
    <org_study_id>C001AMDCLLI</org_study_id>
    <nct_id>NCT03777254</nct_id>
  </id_info>
  <brief_title>Evaluation the Pharmacokinetics,Safety,Tolerability of Single Intravitreal Injection RC28-E in Subjects With Wet Age-Related Macular Degeneration</brief_title>
  <official_title>A Double-center, Open-label,Single Ascending Dose Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Intravitreous Injections of RC28-E (a Chimeric Decoy Receptor Trap Fusion Protein by Dual Blockage of VEGF and FGF-2) in Subjects With Wet Age-Related Macular Degeneration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RemeGen Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RemeGen Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this first-in-human study is to evaluate the safety, tolerability and&#xD;
      pharmacokinetics of single intravitreous injections,single ascending doses, of RC28-E(a&#xD;
      chimeric decoy receptor trap fusion protein by dual blockage of VEGF and FGF-2) in subjects&#xD;
      with wet age-related macular degeneration (wAMD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, non-randomized,double-center phase 1 study evaluating&#xD;
      pharmacokinetics, safety and tolerability of single intravitreal injections of RC28-E in the&#xD;
      patients with AMD.RC28-E is recombinant dual decoy receptor IgG1 Fc-fusion protein,can block&#xD;
      VEGF-A and FGF-2. In preclinical studies suggested that RC28-E might be more effective in&#xD;
      inhibiting pathological angiogenesis than other VEGF antagonists on CNV. Every subject will&#xD;
      only accept one dose. In addition to safety and preliminary efficacy, pharmacokinetics and&#xD;
      immunogenicity of RC28-E will be evaluated as well.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 7, 2019</start_date>
  <completion_date type="Actual">August 20, 2019</completion_date>
  <primary_completion_date type="Actual">August 20, 2019</primary_completion_date>
  <phase>Phase 1</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>Incidence of ocular and systemic adverse events and serious adverse events which are related to RC28-E</measure>
    <time_frame>42 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve(AUC)</measure>
    <time_frame>42 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed maximum plasma concentration (Cmax)</measure>
    <time_frame>42 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach the maximum observed plasma concentration (Tmax)</measure>
    <time_frame>42 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2(Terminal phase half life after single dose)</measure>
    <time_frame>42 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Best Corrected Visual Acuity (BCVA) from baseline</measure>
    <time_frame>42 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Central Retinal Thickness（CRT）from baseline</measure>
    <time_frame>42 days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Neovascular Age-related Macular Degeneration</condition>
  <arm_group>
    <arm_group_label>RC28-E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>&quot;·Experimental:RC28-E 0.25mg Injection:single Intravitreal Injection Intervention: Biological: RC28-E&#xD;
Experimental: RC28-E 0.5mg Injection:single Intravitreal Injection Intervention: Biological: RC28-E&#xD;
Experimental: RC28-E 1.0mg Injection:single Intravitreal Injection Intervention: Biological: RC28-E&#xD;
Experimental: RC28-E 2.0mg Injection:single Intravitreal Injection Intervention: Biological: RC28-E&quot;</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RC28-E</intervention_name>
    <description>RC28-E intravitreous injection 50ul</description>
    <arm_group_label>RC28-E</arm_group_label>
    <other_name>RC28-E is a chimeric decoy receptor trap fusion protein by dual blockage of VEGF and FGF-2.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients or their legal representative signed informed consent;&#xD;
&#xD;
          2. Aged 50 years to 80 years, male or female;&#xD;
&#xD;
          3. Best corrected VA for the studied eye≥34 letters, ≤73 letters(By ETDRS chart);&#xD;
&#xD;
          4. With choroidal neovascular (CNV) lesions secondary to neovascular AMD;&#xD;
&#xD;
          5. If both eyes meet the criteria, severe illness eye will be selected; if both eyes are&#xD;
             the same, the right eye will be selected as the study eye.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of any vitreous hemorrhage with 2 months prior to screening;&#xD;
&#xD;
          2. Presence of scar, fibrosis or atrophy in central foveal of the study eye;&#xD;
&#xD;
          3. Significant refractive media opacity, including cataract, may interfere with visual&#xD;
             assessment;&#xD;
&#xD;
          4. The studied eye suffered pseudoexfoliation syndrome, central retinal vein occlusion,&#xD;
             intraocular hemorrhage resulting in decreased vision, rhegmatogenous retinal&#xD;
             detachment, macular hole, choroidal neovascularization (CNV) for any reason other than&#xD;
             AMD (such as fundus angioid streaks, ocular histoplasmosis, pathologic myopia,&#xD;
             trauma);&#xD;
&#xD;
          5. Afferent pupillary defect(APD);&#xD;
&#xD;
          6. The intraocular pressure is higher than 25mmHg despite medication treatment;&#xD;
&#xD;
          7. Active infectious conjunctivitis, keratitis, scleritis, uveitis and endophthalmitis;&#xD;
&#xD;
          8. Best corrected VA for the studied eye≤19 letters(By ETDRS chart);&#xD;
&#xD;
          9. Topical or grid photocoagulation within 3 months before screening;&#xD;
&#xD;
         10. Uncontrolled diabetes mellitus(fast glucose level≥7.0 mmol/L or ≥11.1 mmol/L 2h after&#xD;
             meal;&#xD;
&#xD;
         11. The studied eye received any intraocular surgery or laser treatment (such as macular&#xD;
             translocation surgery, glaucoma filtering surgery, transpupillary thermotherapy,&#xD;
             foveal photocoagulation surgery, vitrectomy, optic neurotomy, optic nerve sheath&#xD;
             fenestration; But cataract surgery, verteporfin photodynamic therapy, Nd:YAG laser&#xD;
             posterior capsulotomy more than 3 months before screening can be selected;&#xD;
&#xD;
         12. Any eye or whole body received anti-angiogenic drug such as pegaptanib, Aflibercept,&#xD;
             Ranibizumab, Bevacizumab,conbercept within 3 months before baseline visit;&#xD;
&#xD;
         13. Any eye received intraocular injection of corticosteroid drugs (such as triamcinolone&#xD;
             acetonide) within 3 months before screening, or periocular injection of corticosteroid&#xD;
             drugs within 1 months before screening;&#xD;
&#xD;
         14. Allergic to sodium fluorescein, indocyanine green, therapeutic or diagnostic protein&#xD;
             products, and allergic ≥2 drugs and/or non-drugs, or with current allergic diseases;&#xD;
&#xD;
         15. With surgery within one month prior to enrollment, or with unhealed wound, ulcer,&#xD;
             fracture at present;&#xD;
&#xD;
         16. No lens (excluding intraocular lens);&#xD;
&#xD;
         17. Uncontrolled hypertension(defined as those who received the best treatment regimen,&#xD;
             &gt;180 mmHg systolic was measured once, &gt;160 mmHg systolic or &gt; 100 mmHg diastolic was&#xD;
             measured twice in succession);&#xD;
&#xD;
         18. With a history of myocardial infarction within 6 months before screening;&#xD;
&#xD;
         19. With activity disseminated intravascular coagulation and significant bleeding tendency&#xD;
             prior to screening; Using anticoagulants or antiplatelet aggregation drugs in addition&#xD;
             to aspirin/NSAIDs within 14 days before screening;&#xD;
&#xD;
         20. Any uncontrolled clinical disease (such as severe mental, neurological,&#xD;
             cardiovascular, respiratory and other systemic diseases and malignant tumors);&#xD;
&#xD;
         21. Pregnant (blood pregnancy test positive) and lactating women and patients who cannot&#xD;
             take effective contraception(such as intrauterine devices, acyeterion, condoms, etc.)&#xD;
             between study period or 30 days after visit;&#xD;
&#xD;
         22. Patients who participated in or were currently attending other clinical studies within&#xD;
             30 days before screening;&#xD;
&#xD;
         23. The patients is considered unsuitable for enrollment by investigator. &quot;&#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>wenbin wei</last_name>
    <role>Principal Investigator</role>
    <affiliation>BEIJING TONGREN HOSPITAL.CMU</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Tongren Hospital .Cmu</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>December 9, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>April 26, 2021</last_update_submitted>
  <last_update_submitted_qc>April 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2021</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>Macular Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>RC28-E protein</mesh_term>
  </intervention_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/NCT03777254
org study id: C001AMDCLLI
nct id: NCT03777254
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this first-in-human study is to evaluate the safety, tolerability and
      pharmacokinetics of single intravitreous injections,single ascending doses, of RC28-E(a
      chimeric decoy receptor trap fusion protein by dual blockage of VEGF and FGF-2) in subjects
      with wet age-related macular degeneration (wAMD).
This is an open-label, non-randomized,double-center phase 1 study evaluating
      pharmacokinetics, safety and tolerability of single intravitreal injections of RC28-E in the
      patients with AMD.RC28-E is recombinant dual decoy receptor IgG1 Fc-fusion protein,can block
      VEGF-A and FGF-2. In preclinical studies suggested that RC28-E might be more effective in
      inhibiting pathological angiogenesis than other VEGF antagonists on CNV. Every subject will
      only accept one dose. In addition to safety and preliminary efficacy, pharmacokinetics and
      immunogenicity of RC28-E will be evaluated as well.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of ocular and systemic adverse events and serious adverse events which are related to RC28-E
time frame: 42 days
measure: Area under the plasma concentration-time curve(AUC)
time frame: 42 days
measure: Maximum observed maximum plasma concentration (Cmax)
time frame: 42 days
measure: Time to reach the maximum observed plasma concentration (Tmax)
time frame: 42 days
measure: T1/2(Terminal phase half life after single dose)
time frame: 42 days
measure: Change in Best Corrected Visual Acuity (BCVA) from baseline
time frame: 42 days
measure: Change in Central Retinal Thickness（CRT）from baseline
time frame: 42 days
arm group label: RC28-E
arm group type: Experimental
description: "·Experimental:RC28-E 0.25mg Injection:single Intravitreal Injection Intervention: Biological: RC28-E
Experimental: RC28-E 0.5mg Injection:single Intravitreal Injection Intervention: Biological: RC28-E
Experimental: RC28-E 1.0mg Injection:single Intravitreal Injection Intervention: Biological: RC28-E
Experimental: RC28-E 2.0mg Injection:single Intravitreal Injection Intervention: Biological: RC28-E"
intervention type: Biological
intervention name: RC28-E
description: RC28-E intravitreous injection 50ul
arm group label: RC28-E
other name: RC28-E is a chimeric decoy receptor trap fusion protein by dual blockage of VEGF and FGF-2.
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: wenbin wei
role: Principal Investigator
affiliation: BEIJING TONGREN HOSPITAL.CMU
facility: 
country: China
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: RC28-E protein