<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/NCT03829449</url>
  </required_header>
  <id_info>
    <org_study_id>AK581</org_study_id>
    <nct_id>NCT03829449</nct_id>
  </id_info>
  <brief_title>rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study</brief_title>
  <acronym>CONSERVE</acronym>
  <official_title>CONSERVE: rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AKARI Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AKARI Therapeutics</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>
      Patients with diseases requiring complement inhibition who have previously taken part in&#xD;
      Akari clinical trials and who wish to continue to receive rVA576 (Coversin) after their&#xD;
      active participation in the parent trial has completed and patients treated under&#xD;
      compassionate use or named patient arrangements who wish to continue on rVA576 (Coversin)&#xD;
      therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The early termination of this study is a business decision, Akari have made the decision to&#xD;
    close their global Phase III PNH program. The decision was not related to any efficacy, safety&#xD;
    or clinical concerns regarding Coversin/rVA576.&#xD;
  </why_stopped>
  <start_date type="Actual">March 13, 2017</start_date>
  <completion_date type="Actual">August 29, 2020</completion_date>
  <primary_completion_date type="Actual">August 29, 2020</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>Open-label, non-comparative</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Long term safety and efficacy of rVA576 (Coversin) therapy assessed by AEs, SAEs, Standard Lab tests and ECG results.</measure>
    <time_frame>4 years</time_frame>
    <description>To determine the safety profile of long-term rVA576 (Coversin) treatment as assessed by AEs, SAEs, Standard Lab tests and ECG results.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with thrombotic and haemolytic event free status during each 3month time period since the start of the study.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of subjects with thrombotic and haemolytic event free status during each 3month time period since the start of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to thrombotic or haemolytic event since joining this study.</measure>
    <time_frame>4 years</time_frame>
    <description>Time to thrombotic or haemolytic event since joining this study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects who require PRBC transfusion during each 3-month period since the start of the study and over the entire period of the study</measure>
    <time_frame>4 years</time_frame>
    <description>Proportion of subjects who require PRBC transfusion during each 3-month period since the start of the study and over the entire period of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first transfusion since joining the study.</measure>
    <time_frame>4 years</time_frame>
    <description>Time to first transfusion since joining the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with no adverse change in overall scores of Quality of Life using the EORTC QLQ-C30, the EQ-5D-5L and FACIT-F instruments at each 3-month time period since the start of the study.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of subjects with no adverse change in overall scores of Quality of Life using the EORTC QLQ-C30, the EQ-5D-5L and FACIT-F instruments at each 3-month time period since the start of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with serum Lactate Dehydrogenase (LDH) &lt;1.8, &gt;1.8 to 2.4, &gt;2.4 to 3, and &gt;3 times the upper limit of normal (ULN) at each 3-month time period since the start of the study.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of subjects with serum Lactate Dehydrogenase (LDH) &lt;1.8, &gt;1.8 to 2.4, &gt;2.4 to 3, and &gt;3 times the upper limit of normal (ULN) at each 3-month time period since the start of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with median serum Lactate Dehydrogenase (LDH) &lt;1.8, &gt;1.8 to 2.4, &gt;2.4 to 3, and &gt;3 times the upper limit of normal (ULN) over the entire duration of the study.</measure>
    <time_frame>4 years</time_frame>
    <description>Proportion of subjects with median serum Lactate Dehydrogenase (LDH) &lt;1.8, &gt;1.8 to 2.4, &gt;2.4 to 3, and &gt;3 times the upper limit of normal (ULN) over the entire duration of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of transfusion-independent subjects at each 3-month time point, with haemoglobin (g/L) above the baseline haemoglobin value they had at the start of the trial from which they entered CONSERVE</measure>
    <time_frame>3 monthly</time_frame>
    <description>Proportion of transfusion-independent subjects at each 3-month time point, with haemoglobin (g/L) above the baseline haemoglobin value they had at the start of the trial from which they entered CONSERVE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of transfusion-independent subjects over the entire duration of the study with mean haemoglobin (g/L) above the baseline haemoglobin value they had at the start of the trial from which they entered CONSERVE</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of transfusion-independent subjects over the entire duration of the study with mean haemoglobin (g/L) above the baseline haemoglobin value they had at the start of the trial from which they entered CONSERVE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study.</measure>
    <time_frame>4 years</time_frame>
    <description>Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study.</measure>
    <time_frame>4 years</time_frame>
    <description>Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Major Adverse Vascular Events (MAVE) over the entire period of the study.</measure>
    <time_frame>4 years</time_frame>
    <description>Number of Major Adverse Vascular Events (MAVE) over the entire period of the study.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Paroxysmal Nocturnal Hemoglobinuria</condition>
  <arm_group>
    <arm_group_label>rVA576 Coversin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The study population will consist of patients who have completed participation in clinical trials under other Akari protocols and who wish to continue to receive rVA576 (Coversin) for up to 4 years.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rVA576 (Coversin)</intervention_name>
    <description>The study population will consist of patients who have completed participation in clinical trials under other Akari protocols and who wish to continue to receive rVA576 (Coversin).</description>
    <arm_group_label>rVA576 Coversin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients 18 years and above treated with rVA576 (Coversin) under other Akari clinical&#xD;
             trial protocols and wish to remain on rVA576 (Coversin) at the conclusion of that&#xD;
             trial.&#xD;
&#xD;
          2. In the opinion of the treating responsible clinician patient is receiving clinical&#xD;
             benefit from continued treatment with study drug.&#xD;
&#xD;
          3. Evidence of sustained complement inhibition by CH50 assay. .&#xD;
&#xD;
          4. Women of childbearing potential (WOCBP) must agree to use effective contraception&#xD;
             consistently throughout the study and have a negative pregnancy test at screening and&#xD;
             a negative urine pregnancy test per the schedule of visits. Women cannot donate their&#xD;
             eggs. Women are considered post-menopausal and not of childbearing potential if they&#xD;
             have had 12 months of amenorrhea or have had surgical bilateral oophorectomy (with or&#xD;
             without hysterectomy) or tubal ligation at least six weeks previously.&#xD;
&#xD;
          5. Males with a childbearing potential partner must agree to use effective contraception&#xD;
             consistently OR have had a vasectomy&#xD;
&#xD;
          6. Weight ≥50-100kg&#xD;
&#xD;
          7. Willing to receive appropriate prophylaxis against Neisseria meningitidis infection,&#xD;
             by both immunisation and continuous or intermittent antibiotics&#xD;
&#xD;
          8. The patient is willing to give voluntary written informed consent&#xD;
&#xD;
          9. The patient is willing in the process of preparation and self-administration of the&#xD;
             study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient experienced any safety event in the previous study protocol, which puts the&#xD;
             patient at unacceptable risk in current protocol as judged by the investigator and&#xD;
             sponsor.&#xD;
&#xD;
          2. Patient is unwilling to complete the Quality of Life instruments and diary card&#xD;
&#xD;
          3. Active meningococcal infection (section 4.3.1 for additional information)&#xD;
&#xD;
          4. Any other reason for which, in the opinion of the Investigator, it would not be in the&#xD;
             interests of the patient to remain on rVA576 (Coversin).&#xD;
&#xD;
          5. If female, the subject is pregnant or lactating or intending to become pregnant&#xD;
             before, during, or within 90 days after last dose; or intending to donate ova during&#xD;
             such time period.&#xD;
&#xD;
          6. If male, the subject intends to donate sperm while on the study this study or for 90&#xD;
             days after last dose.&#xD;
&#xD;
          7. Failure to satisfy the Investigator of fitness to participate for any other reason or&#xD;
             any other condition which, in the opinion of the investigator, could increase the&#xD;
             subject's risk by participating in the study or confound the outcome of the study.&#xD;
&#xD;
          8. Use of prohibited medication&#xD;
&#xD;
          9. The subject has a history of drug abuse (defined as any illicit drug use) or a history&#xD;
             of alcohol abuse.&#xD;
&#xD;
         10. Participation in other clinical trials with investigational product.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Instytut Hematologii i Transfuzjologii</name>
      <address>
        <city>Warsaw</city>
        <zip>02-776</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>June 22, 2021</last_update_submitted>
  <last_update_submitted_qc>June 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 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>Hemoglobinuria</mesh_term>
    <mesh_term>Hemoglobinuria, Paroxysmal</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03829449
org study id: AK581
nct id: NCT03829449
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with diseases requiring complement inhibition who have previously taken part in
      Akari clinical trials and who wish to continue to receive rVA576 (Coversin) after their
      active participation in the parent trial has completed and patients treated under
      compassionate use or named patient arrangements who wish to continue on rVA576 (Coversin)
      therapy.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open-label, non-comparative
primary purpose: Treatment
masking: None (Open Label)
measure: Long term safety and efficacy of rVA576 (Coversin) therapy assessed by AEs, SAEs, Standard Lab tests and ECG results.
time frame: 4 years
description: To determine the safety profile of long-term rVA576 (Coversin) treatment as assessed by AEs, SAEs, Standard Lab tests and ECG results.
measure: Proportion of subjects with thrombotic and haemolytic event free status during each 3month time period since the start of the study.
time frame: 12 weeks
description: Proportion of subjects with thrombotic and haemolytic event free status during each 3month time period since the start of the study.
measure: Time to thrombotic or haemolytic event since joining this study.
time frame: 4 years
description: Time to thrombotic or haemolytic event since joining this study.
measure: Proportion of subjects who require PRBC transfusion during each 3-month period since the start of the study and over the entire period of the study
time frame: 4 years
description: Proportion of subjects who require PRBC transfusion during each 3-month period since the start of the study and over the entire period of the study
measure: Time to first transfusion since joining the study.
time frame: 4 years
description: Time to first transfusion since joining the study.
measure: Proportion of subjects with no adverse change in overall scores of Quality of Life using the EORTC QLQ-C30, the EQ-5D-5L and FACIT-F instruments at each 3-month time period since the start of the study.
time frame: 12 weeks
description: Proportion of subjects with no adverse change in overall scores of Quality of Life using the EORTC QLQ-C30, the EQ-5D-5L and FACIT-F instruments at each 3-month time period since the start of the study.
measure: Proportion of subjects with serum Lactate Dehydrogenase (LDH) <1.8, >1.8 to 2.4, >2.4 to 3, and >3 times the upper limit of normal (ULN) at each 3-month time period since the start of the study.
time frame: 12 weeks
description: Proportion of subjects with serum Lactate Dehydrogenase (LDH) <1.8, >1.8 to 2.4, >2.4 to 3, and >3 times the upper limit of normal (ULN) at each 3-month time period since the start of the study.
measure: Proportion of subjects with median serum Lactate Dehydrogenase (LDH) <1.8, >1.8 to 2.4, >2.4 to 3, and >3 times the upper limit of normal (ULN) over the entire duration of the study.
time frame: 4 years
description: Proportion of subjects with median serum Lactate Dehydrogenase (LDH) <1.8, >1.8 to 2.4, >2.4 to 3, and >3 times the upper limit of normal (ULN) over the entire duration of the study.
measure: Proportion of transfusion-independent subjects at each 3-month time point, with haemoglobin (g/L) above the baseline haemoglobin value they had at the start of the trial from which they entered CONSERVE
time frame: 3 monthly
description: Proportion of transfusion-independent subjects at each 3-month time point, with haemoglobin (g/L) above the baseline haemoglobin value they had at the start of the trial from which they entered CONSERVE
measure: Proportion of transfusion-independent subjects over the entire duration of the study with mean haemoglobin (g/L) above the baseline haemoglobin value they had at the start of the trial from which they entered CONSERVE
time frame: 12 weeks
description: Proportion of transfusion-independent subjects over the entire duration of the study with mean haemoglobin (g/L) above the baseline haemoglobin value they had at the start of the trial from which they entered CONSERVE
measure: Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study.
time frame: 4 years
description: Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study.
measure: Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study.
time frame: 4 years
description: Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study.
measure: Number of Major Adverse Vascular Events (MAVE) over the entire period of the study.
time frame: 4 years
description: Number of Major Adverse Vascular Events (MAVE) over the entire period of the study.
arm group label: rVA576 Coversin
arm group type: Experimental
description: The study population will consist of patients who have completed participation in clinical trials under other Akari protocols and who wish to continue to receive rVA576 (Coversin) for up to 4 years.
intervention type: Drug
intervention name: rVA576 (Coversin)
description: The study population will consist of patients who have completed participation in clinical trials under other Akari protocols and who wish to continue to receive rVA576 (Coversin).
arm group label: rVA576 Coversin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Poland
responsible party type: Sponsor
mesh term: Hemoglobinuria
mesh term: Hemoglobinuria, Paroxysmal
sharing ipd: No