<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/NCT03777332</url>
  </required_header>
  <id_info>
    <org_study_id>APL2-103</org_study_id>
    <nct_id>NCT03777332</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Safety of Intravitreal APL-2 in Patients Diagnosed With Geographic Atrophy</brief_title>
  <official_title>A 24-Month Phase Ib Multi-Center, Open Label, Single Arm Study to Evaluate the Safety of Intravitreal APL-2 Therapy in Patients Diagnosed With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Apellis Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Apellis Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Safety Assessment of APL-2 in Patients with Geographic Atrophy&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 5, 2018</start_date>
  <completion_date type="Actual">April 1, 2021</completion_date>
  <primary_completion_date type="Actual">April 1, 2021</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>Incidence and Severity of Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>25 Months</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Geographic Atrophy</condition>
  <arm_group>
    <arm_group_label>(Cohort 1) Pegcetacoplan, 15 mg/100 μL, monthly for up to 60 months</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>(Cohort 2) Pegcetacoplan, 15 mg/100 μL, monthly for up to 36 months</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>(Cohort 2) Pegcetacoplan, 15 mg/100 μL, every other month for up to 36 months</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PEGCETACOPLAN (APL-2)</intervention_name>
    <description>Complement (C3) Inhibitor</description>
    <arm_group_label>(Cohort 1) Pegcetacoplan, 15 mg/100 μL, monthly for up to 60 months</arm_group_label>
    <arm_group_label>(Cohort 2) Pegcetacoplan, 15 mg/100 μL, every other month for up to 36 months</arm_group_label>
    <arm_group_label>(Cohort 2) Pegcetacoplan, 15 mg/100 μL, monthly for up to 36 months</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: Cohort 1&#xD;
&#xD;
        The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria,&#xD;
        the eye with the worst normal luminance best-corrected visual acuity (NL-BCVA) at the&#xD;
        screening visit will be designated as the study eye. If both eyes have the same visual&#xD;
        acuity, the eye with the larger GA lesion will be selected as the study eye. If both eyes&#xD;
        have the same GA lesion size, the right eye will be selected as the study eye.&#xD;
&#xD;
        Ocular- specific inclusion criteria apply to the study eye only, unless otherwise&#xD;
        specified.&#xD;
&#xD;
          1. Age ≥ 60 years.&#xD;
&#xD;
          2. Normal Luminance best corrected visual acuity of between 35 and 5 letters using Early&#xD;
             Treatment Diabetic Retinopathy Study (ETDRS) charts (approximately between 20/200 and&#xD;
             20/800 Snellen equivalent).&#xD;
&#xD;
          3. Clinical diagnosis of GA of the macula secondary to AMD as determined by the&#xD;
             Investigator and confirmed by the Reading Center.&#xD;
&#xD;
          4. The GA lesion must meet the following criteria as determined by the central reading&#xD;
             center's assessment of Fundus Autofluorescence (FAF) imaging at screening:&#xD;
&#xD;
               1. Total GA area must be ≥ 2.5 (1 disk areas [DA]).&#xD;
&#xD;
               2. If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA), with&#xD;
                  the overall aggregate area of GA as specified above in 4a.&#xD;
&#xD;
          5. Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit&#xD;
             the collection of good quality images as determined by the Investigator.&#xD;
&#xD;
          6. Female subjects must be:&#xD;
&#xD;
               1. Women of non-child-bearing potential (WONCBP), or&#xD;
&#xD;
               2. Women of child-bearing potential (WOCBP) with a negative serum pregnancy test at&#xD;
                  screening and must agree to use protocol defined methods of contraception for the&#xD;
                  duration of the study and refrain from breastfeeding for the duration of the&#xD;
                  study.&#xD;
&#xD;
          7. Males with female partners of child-bearing potential must agree to use protocol&#xD;
             defined methods of contraception and agree to refrain from donating sperm for the&#xD;
             duration of the study.&#xD;
&#xD;
          8. Willing and able to give informed consent and to comply with the study procedures and&#xD;
             assessments.&#xD;
&#xD;
        Exclusion Criteria: Cohort 1&#xD;
&#xD;
        Ocular specific exclusion criteria apply to the study eye only, unless otherwise specified.&#xD;
&#xD;
          1. GA secondary to a condition other than AMD such as Stargardt disease, cone rod&#xD;
             dystrophy or toxic maculopathies like plaquenil maculopathy in either eye.&#xD;
&#xD;
          2. Spherical equivalent of the refractive error demonstrating &gt; 6 diopters of myopia or&#xD;
             an axial length &gt;26 mm.&#xD;
&#xD;
          3. Any history or active choroidal neovascularization (CNV), associated with AMD or any&#xD;
             other cause, including any evidence of retinal pigment epithelium rips or evidence of&#xD;
             neovascularization anywhere based on SD-OCT imaging and/or fluorescein angiography as&#xD;
             assessed by the Reading Center.&#xD;
&#xD;
          4. Presence of an active ocular disease that in the opinion of the Investigator&#xD;
             compromises or confounds visual function, including but not limited to, uveitis, other&#xD;
             macular diseases (e.g. clinically significant epiretinal membrane [ERM], full&#xD;
             thickness macular hole) or uncontrolled glaucoma/ocular hypertension). Benign&#xD;
             conditions in the opinion of the Investigator such as peripheral retina dystrophy are&#xD;
             not exclusionary.&#xD;
&#xD;
          5. Intraocular surgery (including lens replacement surgery) within 3 months prior to&#xD;
             enrollment.&#xD;
&#xD;
          6. History of laser therapy in the macular region.&#xD;
&#xD;
          7. History of intraocular injection within 3 months prior to the screening visit.&#xD;
&#xD;
          8. Aphakia or absence of the posterior capsule. Note: Yttrium-Aluminum Garnet YAG laser&#xD;
             posterior capsulotomy for posterior capsule opacification done at least 60 days prior&#xD;
             to screening is not exclusionary.&#xD;
&#xD;
          9. Any ocular condition other than GA secondary to AMD that may require surgery or&#xD;
             medical intervention during the study period or, in the opinion of the Investigator,&#xD;
             could compromise visual function during the study period.&#xD;
&#xD;
         10. Any contraindication to IVT injection including current ocular or periocular&#xD;
             infection.&#xD;
&#xD;
         11. Participation in any systemic experimental treatment or any other systemic&#xD;
             investigational new drug including within 6 weeks or 5 half-lives of the active&#xD;
             ingredient (whichever is longer) prior to the start of study treatment. Note: clinical&#xD;
             trials solely involving observation, over-the-counter vitamins, supplements, or diets&#xD;
             are not exclusionary.&#xD;
&#xD;
         12. Medical or psychiatric conditions that, in the opinion of the Investigator, make&#xD;
             consistent follow-up over the 60-month treatment period unlikely, or would make the&#xD;
             subject an unsafe study candidate.&#xD;
&#xD;
         13. Any screening laboratory value (hematology, serum chemistry or urinalysis) that in the&#xD;
             opinion of the Investigator is clinically significant and not suitable for study&#xD;
             participation.&#xD;
&#xD;
         14. Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to&#xD;
             pegcetacoplan or any of the excipients in pegcetacoplan solution.&#xD;
&#xD;
        Inclusion Criteria: Cohort 2&#xD;
&#xD;
        Ocular-specific inclusion criteria apply to the study eye only.&#xD;
&#xD;
          1. Participated in the APL2-303 (Derby, NCT03525613) or APL2-304 (Oaks, NCT03525600)&#xD;
             study with completion of the Month 24 visit and have been invited to participate in&#xD;
             this study.&#xD;
&#xD;
             a. Subjects who did not discontinue treatment but missed the Month 24 visit are also&#xD;
             eligible to participate in this study.&#xD;
&#xD;
          2. Clarity of ocular media, adequate pupillary dilation, and fixation to permit the&#xD;
             collection of good quality images as determined by the investigator.&#xD;
&#xD;
          3. Female subjects must be:&#xD;
&#xD;
               1. Women of non-child-bearing potential (WONCBP), or&#xD;
&#xD;
               2. Women of child-bearing potential (WOCBP) with a negative serum pregnancy test at&#xD;
                  screening and must agree to use protocol defined methods of contraception for the&#xD;
                  duration of the study and 90 days after their last dose of pegcetacoplan, and&#xD;
                  refrain from breastfeeding for the duration of the study.&#xD;
&#xD;
          4. Males with female partners of child-bearing potential must agree to use protocol&#xD;
             defined methods of contraception and agree to refrain from donating sperm for the&#xD;
             duration of the study and for 90 days after their last dose of pegcetacoplan.&#xD;
&#xD;
          5. Willing and able to give informed consent to comply with the study procedures and&#xD;
             assessments&#xD;
&#xD;
        Exclusion Criteria: Cohort 2&#xD;
&#xD;
        Ocular-specific exclusion criteria apply to the study eye only, unless otherwise specified.&#xD;
&#xD;
          1. Subjects who discontinued the study drug prior to Month 24 and remained in the APL2-&#xD;
             303 (Derby, NCT 03525613) or APL2-304 (Oaks, NCT03525600 study for safety assessments.&#xD;
             Temporary pause of the study drug is not exclusionary.&#xD;
&#xD;
          2. Presence of an active ocular disease that, in the opinion of the investigator,&#xD;
             compromises or confounds visual function, including, but not limited to, macular hole&#xD;
             or other macular diseases (eg, clinically significant epiretinal membrane). Benign&#xD;
             conditions in the opinion of the investigator such as peripheral retinal dystrophy are&#xD;
             not exclusionary.&#xD;
&#xD;
          3. Any contraindication to IVT injection including current ocular or periocular&#xD;
             infection.&#xD;
&#xD;
          4. Medical or psychiatric conditions that, in the opinion of the investigator, is&#xD;
             clinically significant and not suitable for study participation or consistent&#xD;
             follow-up.&#xD;
&#xD;
          5. Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to&#xD;
             pegcetacoplan or any of the excipients in pegcetacoplan solution.&#xD;
&#xD;
          6. Pregnancy, breastfeeding, or positive pregnancy test.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>California Retina Consultants</name>
      <address>
        <city>Bakersfield</city>
        <state>California</state>
        <zip>93309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Vitreous Associates Medical Group</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Retina Partners</name>
      <address>
        <city>Encino</city>
        <state>California</state>
        <zip>91436</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ophthalmic Consultants of Boston</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Houston</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>November 8, 2021</last_update_submitted>
  <last_update_submitted_qc>November 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 10, 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>Geographic Atrophy</mesh_term>
    <mesh_term>Atrophy</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/NCT03777332
org study id: APL2-103
nct id: NCT03777332
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Safety Assessment of APL-2 in Patients with Geographic Atrophy
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence and Severity of Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs)
time frame: 25 Months
arm group label: (Cohort 1) Pegcetacoplan, 15 mg/100 μL, monthly for up to 60 months
arm group type: Experimental
arm group label: (Cohort 2) Pegcetacoplan, 15 mg/100 μL, monthly for up to 36 months
arm group type: Experimental
arm group label: (Cohort 2) Pegcetacoplan, 15 mg/100 μL, every other month for up to 36 months
arm group type: Experimental
intervention type: Drug
intervention name: PEGCETACOPLAN (APL-2)
description: Complement (C3) Inhibitor
arm group label: (Cohort 1) Pegcetacoplan, 15 mg/100 μL, monthly for up to 60 months
arm group label: (Cohort 2) Pegcetacoplan, 15 mg/100 μL, every other month for up to 36 months
arm group label: (Cohort 2) Pegcetacoplan, 15 mg/100 μL, monthly for up to 36 months
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Geographic Atrophy
mesh term: Atrophy