<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/NCT03814291</url>
  </required_header>
  <id_info>
    <org_study_id>CIBI302A101</org_study_id>
    <nct_id>NCT03814291</nct_id>
  </id_info>
  <brief_title>A Dose Escalation Study of IBI302 in Patients With Wet Age-related Macular Degeneration</brief_title>
  <official_title>A Dose Escalation Phase I Clinical Study to Evaluate the Tolerability and Safety of IBI302 in Patients With Wet Age-related Macular Degeneration (AMD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Innovent Biologics (Suzhou) Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Innovent Biologics (Suzhou) Co. Ltd.</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>
      This study is designed for single-center, open-label, dose escalation phase I trial to&#xD;
      evaluate the safety and tolerability of a single intravitreal injection of IBI302 in patients&#xD;
      with wet AMD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">April 16, 2019</start_date>
  <completion_date type="Anticipated">April 5, 2020</completion_date>
  <primary_completion_date type="Anticipated">February 21, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</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 evaluation indicators</measure>
    <time_frame>Baseline to Day43</time_frame>
    <description>Decreasing of BCVA; b) Changes in intraocular pressure compared with baseline; c) Incidence, relatedness and severity of all adverse events, treatment emergent adverse events and serious adverse events;</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy evaluation indicators</measure>
    <time_frame>Baseline to Day43</time_frame>
    <description>Changes in central subfield thickness by OCT compared with baseline; b) Changes in CNV area by FA compared with baseline; c) Changes in BCVA compared with baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity evaluation indicators</measure>
    <time_frame>Baseline to Day43</time_frame>
    <description>Positive rate of anti-drug antibody and neutralizing antibody</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The area under the drug-time curve from 0 to time t (AUC0-t)</measure>
    <time_frame>Baseline to Day43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The area under the curve at the time of 0-infinity (AUC0-∞)</measure>
    <time_frame>Baseline to Day43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The peak concentration (Cmax)</measure>
    <time_frame>Baseline to Day43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The peak time (Tmax)</measure>
    <time_frame>Baseline to Day43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance rate (CL)</measure>
    <time_frame>Baseline to Day43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (t1/2)</measure>
    <time_frame>Baseline to Day43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Free and total VEGF concentration</measure>
    <time_frame>Baseline to Day43</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Neovascular Age-related Macular Degeneration</condition>
  <arm_group>
    <arm_group_label>cohort 1 IBI302 treated with first dose level of IBI302</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort 2 IBI302 treated with second dose level of IBI302</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort 3 IBI302 treated with third dose level of IBI302</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort 4 IBI302 treated with fourth dose level of IBI302</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort 5 IBI302 treated with fifth dose level of IBI302</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort 6 IBI302 treated with sixth dose level of IBI302</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI302</intervention_name>
    <description>0.05mg/eye;Intraocular injection</description>
    <arm_group_label>cohort 1 IBI302 treated with first dose level of IBI302</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI302</intervention_name>
    <description>0.15mg/eye;Intraocular injection</description>
    <arm_group_label>cohort 2 IBI302 treated with second dose level of IBI302</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI302</intervention_name>
    <description>0.5mg/eye;Intraocular injection</description>
    <arm_group_label>cohort 3 IBI302 treated with third dose level of IBI302</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI302</intervention_name>
    <description>1mg/eye;Intraocular injection</description>
    <arm_group_label>cohort 4 IBI302 treated with fourth dose level of IBI302</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI302</intervention_name>
    <description>2mg/eye;Intraocular injection</description>
    <arm_group_label>cohort 5 IBI302 treated with fifth dose level of IBI302</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI302</intervention_name>
    <description>4mg/eye;Intraocular injection</description>
    <arm_group_label>cohort 6 IBI302 treated with sixth dose level of IBI302</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patient ≥ 50 yrs. of age.&#xD;
&#xD;
          2. Active subfoveal CNV secondary to wet AMD, with lesion size ≤ 12 optic discs in the&#xD;
             study eye.&#xD;
&#xD;
          3. BCVA score of 10-73 letters using ETDRS charts (in 4 meters) in the study eye.&#xD;
&#xD;
          4. Central macular sub-field thickness according to OCT of at least 250 micron.&#xD;
&#xD;
          5. Clear stereoscopic fundus photography is obtained while the lens or other media is&#xD;
             clear.&#xD;
&#xD;
          6. Female subjects of childbearing age or male subjects with childbearing age female&#xD;
             partner agree to take effective contraceptive measures from the screening period to 3&#xD;
             months after the end of treatment.&#xD;
&#xD;
          7. Willing and able to sign informed consent form and comply with visit and study&#xD;
             procedures per protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of other causes of CNV other than wet AMD in the study eye.&#xD;
&#xD;
          2. Presence of active diabetic retinopathy in the study eye.&#xD;
&#xD;
          3. Presence of uncontrolled glaucoma in the study eye (defined as IOP≥30mmHg despite the&#xD;
             standardized treatment).&#xD;
&#xD;
          4. Prior retinal detachment in the study eye.&#xD;
&#xD;
          5. Prior any treatment of following in the study eye:&#xD;
&#xD;
               1. Anti-VEGF therapy within 6 months prior to screening;&#xD;
&#xD;
               2. Anti-complement therapy;&#xD;
&#xD;
               3. Laser photocoagulation;&#xD;
&#xD;
               4. Photodynamic therapy;&#xD;
&#xD;
               5. Transpupillary thermotherapy&#xD;
&#xD;
               6. Intraocular surgery;&#xD;
&#xD;
               7. Intraocular or periocular glucocorticoid injection therapy within 6 months prior&#xD;
                  to enrollment;&#xD;
&#xD;
          6. Presence of any non-AMD disease that may affect visual acuity in the study eye&#xD;
&#xD;
          7. Prior anti-VEGF therapy within 1 month before study drug administration or plan of&#xD;
             above anti-VEGF therapy in the non-study eye during the whole study.&#xD;
&#xD;
          8. Oral steroid drugs within 1 month before study drug administration.&#xD;
&#xD;
          9. Presence of active intraocular or periocular inflammation or infection.&#xD;
&#xD;
         10. Diabetic patients have any of the following conditions:&#xD;
&#xD;
               1. Microvascular and macrovascular complications;&#xD;
&#xD;
               2. HbA1c&gt;7.5% when screening;&#xD;
&#xD;
               3. Receiving more than two oral hypoglycemic agents;&#xD;
&#xD;
               4. Receiving insulin or GLP-1 receptor agonist;&#xD;
&#xD;
         11. Hypertension (defined as systolic blood pressure &gt;140 mmHg or diastolic blood pressure&#xD;
             &gt;90 mmHg despite standard treatment);&#xD;
&#xD;
         12. Presence of any following laboratory abnormality:&#xD;
&#xD;
               1. PLT&lt;100×109/L, INR≥1.5ULN, APTT≥ 10 seconds more than ULN;&#xD;
&#xD;
               2. ALT or AST &gt;2ULN;&#xD;
&#xD;
               3. Cr or Ur&gt;1.5ULN;&#xD;
&#xD;
         13. Large or medium surgery, or unhealed surgical incisions, ulcers or fractures within 1&#xD;
             month before study drug administration.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>February 10, 2020</last_update_submitted>
  <last_update_submitted_qc>February 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2020</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>Immunoglobulin Fc Fragments</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/NCT03814291
org study id: CIBI302A101
nct id: NCT03814291
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study is designed for single-center, open-label, dose escalation phase I trial to
      evaluate the safety and tolerability of a single intravitreal injection of IBI302 in patients
      with wet AMD.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety evaluation indicators
time frame: Baseline to Day43
description: Decreasing of BCVA; b) Changes in intraocular pressure compared with baseline; c) Incidence, relatedness and severity of all adverse events, treatment emergent adverse events and serious adverse events;
measure: Efficacy evaluation indicators
time frame: Baseline to Day43
description: Changes in central subfield thickness by OCT compared with baseline; b) Changes in CNV area by FA compared with baseline; c) Changes in BCVA compared with baseline.
measure: Immunogenicity evaluation indicators
time frame: Baseline to Day43
description: Positive rate of anti-drug antibody and neutralizing antibody
measure: The area under the drug-time curve from 0 to time t (AUC0-t)
time frame: Baseline to Day43
measure: The area under the curve at the time of 0-infinity (AUC0-∞)
time frame: Baseline to Day43
measure: The peak concentration (Cmax)
time frame: Baseline to Day43
measure: The peak time (Tmax)
time frame: Baseline to Day43
measure: Clearance rate (CL)
time frame: Baseline to Day43
measure: Half-life (t1/2)
time frame: Baseline to Day43
measure: Free and total VEGF concentration
time frame: Baseline to Day43
arm group label: cohort 1 IBI302 treated with first dose level of IBI302
arm group type: Experimental
arm group label: cohort 2 IBI302 treated with second dose level of IBI302
arm group type: Experimental
arm group label: cohort 3 IBI302 treated with third dose level of IBI302
arm group type: Experimental
arm group label: cohort 4 IBI302 treated with fourth dose level of IBI302
arm group type: Experimental
arm group label: cohort 5 IBI302 treated with fifth dose level of IBI302
arm group type: Experimental
arm group label: cohort 6 IBI302 treated with sixth dose level of IBI302
arm group type: Experimental
intervention type: Drug
intervention name: IBI302
description: 0.05mg/eye;Intraocular injection
arm group label: cohort 1 IBI302 treated with first dose level of IBI302
intervention type: Drug
intervention name: IBI302
description: 0.15mg/eye;Intraocular injection
arm group label: cohort 2 IBI302 treated with second dose level of IBI302
intervention type: Drug
intervention name: IBI302
description: 0.5mg/eye;Intraocular injection
arm group label: cohort 3 IBI302 treated with third dose level of IBI302
intervention type: Drug
intervention name: IBI302
description: 1mg/eye;Intraocular injection
arm group label: cohort 4 IBI302 treated with fourth dose level of IBI302
intervention type: Drug
intervention name: IBI302
description: 2mg/eye;Intraocular injection
arm group label: cohort 5 IBI302 treated with fifth dose level of IBI302
intervention type: Drug
intervention name: IBI302
description: 4mg/eye;Intraocular injection
arm group label: cohort 6 IBI302 treated with sixth dose level of IBI302
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Immunoglobulin Fc Fragments