<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/NCT04482686</url>
  </required_header>
  <id_info>
    <org_study_id>PRG-049</org_study_id>
    <nct_id>NCT04482686</nct_id>
  </id_info>
  <brief_title>Trial of Combination Therapy to Treat COVID-19 Infection</brief_title>
  <official_title>A Phase I Double-Blind Randomized Placebo-Controlled Trial of Combination Therapy to Treat COVID-19 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ProgenaBiome</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Topelia Therapeutics</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>ProgenaBiome</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this trial patients will be treated with either a combination of therapies to treat&#xD;
      COVID-19 or a placebo. Treatment will last 10 days, and patients will be followed for 6&#xD;
      months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients in this trial will undergo treatment for 10 days with either a combination of&#xD;
      therapies or placebo. They will then be followed for an additional 20 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 9, 2020</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">May 2022</primary_completion_date>
  <phase>Phase 1</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to Non-Infectivity by RT-PCR</measure>
    <time_frame>6 months</time_frame>
    <description>Time to negative RT-PRC result indicating that patient is no longer infective</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Symptom progression in days as measured by NEWS scoring system (National Early Warning Score)</measure>
    <time_frame>6 months</time_frame>
    <description>Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Symptom improvement as measured by NEWS scoring system (National Early Warning Score)</measure>
    <time_frame>6 months</time_frame>
    <description>Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy of Treatment as measured by Titer</measure>
    <time_frame>6 months</time_frame>
    <description>Patients will have serum stored for titer testing to compare antibody levels over time</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy of Treatment as measured by RT-PCR</measure>
    <time_frame>10 days</time_frame>
    <description>Number of patients testing negative for SARS-CoV-2 by RT-PCR after 10 days of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of Treatment as Measured by D-Dimer</measure>
    <time_frame>6 Months</time_frame>
    <description>Blood D-Dimer levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Treatment as Measured by Pro-Calcitonin</measure>
    <time_frame>6 Months</time_frame>
    <description>Blood Pro-Calcitonin levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Treatment as Measured by C-Reactive Protein</measure>
    <time_frame>6 Months</time_frame>
    <description>Blood CRP levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Treatment as Measured by Ferritin</measure>
    <time_frame>6 Months</time_frame>
    <description>Blood ferritin levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Treatment as Measured by Liver Enzymes</measure>
    <time_frame>6 Months</time_frame>
    <description>Blood enzyme levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Treatment as Measured by Complete Blood Count</measure>
    <time_frame>6 Months</time_frame>
    <description>CBC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Treatment as Measured by Electrolyte Levels</measure>
    <time_frame>6 Months</time_frame>
    <description>Blood electrolytes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Treatment as Measured by Treatment Related Adverse Events</measure>
    <time_frame>6 months</time_frame>
    <description>Presence or absence of Grade 3 or high treatment related adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>COVID</condition>
  <condition>Covid-19</condition>
  <condition>Corona Virus Infection</condition>
  <condition>Coronavirus Infection</condition>
  <condition>Coronavirus-19</condition>
  <condition>SARS-CoV2</condition>
  <condition>SARS-CoV Infection</condition>
  <arm_group>
    <arm_group_label>Active Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with a combination of Ivermectin, Doxycycline, Zinc, Vitamin D3 and Vitamin C</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo and Vitamin D3, Vitamin C, and Zinc</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivermectin</intervention_name>
    <description>Treatment days 1, 4, and 8</description>
    <arm_group_label>Active Arm</arm_group_label>
    <other_name>Soolantra, Stromectol, Sklice</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxycycline Hcl</intervention_name>
    <description>10 day treatment</description>
    <arm_group_label>Active Arm</arm_group_label>
    <other_name>Doxy-100, Monodox, Oracea, Targadox, Acticlate, Morgidox, Avidoxy, Doryx MPC, Mondoxyne NL, Dory</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Zinc</intervention_name>
    <description>10 Day treatment</description>
    <arm_group_label>Active Arm</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Zinc sulphate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D3</intervention_name>
    <description>10 day treatment</description>
    <arm_group_label>Active Arm</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>cholecalciferol-D3</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin C</intervention_name>
    <description>10 day treatment</description>
    <arm_group_label>Active Arm</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>L-ascorbic acid</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent, demonstrating that the subject understands the procedures&#xD;
             required for the study and the purpose of the study&#xD;
&#xD;
          2. Healthy male or female subjects at least 18 years of age&#xD;
&#xD;
          3. Diabetic and obese (BMI &gt; 30) patients will be included in the Trial but randomization&#xD;
             will be stratified.&#xD;
&#xD;
          4. Positive test for COVID-19 by RT-PCR or rapid antigen test at screening&#xD;
&#xD;
          5. Subjects must agree to practice at least two highly effective methods of birth control&#xD;
             for the duration of the study. One of these must be a barrier method. Exceptions for&#xD;
             females and partners of females that are not of childbearing potential. (e.g.&#xD;
             surgically sterilized, post-menopausal)&#xD;
&#xD;
          6. Subjects must agree they will attend the treatment facility daily for 10d in the event&#xD;
             of failure to attend, the patient will be visited at their home to collect the nasal&#xD;
             swab and review data.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Refusal to sign informed consent form&#xD;
&#xD;
          2. Negative test for COVID-19 by RT-PCR at screening&#xD;
&#xD;
          3. Severe disease symptomatically including pneumonia, respiratory distress, tachypnea,&#xD;
             shortness of breath, temperature &gt; 104.0 degrees F, pleuritic pain, or frequent cough.&#xD;
&#xD;
          4. Known drug allergy to any of the investigational medications&#xD;
&#xD;
          5. Currently taking medication with known drug interactions with investigational&#xD;
             medications, found in Appendix II&#xD;
&#xD;
          6. Prescription or other antiviral medications&#xD;
&#xD;
          7. Any comorbidities which constitute health risk for the subject including known cardiac&#xD;
             arrhythmias - but will be limited to those on hydroxychloroquine&#xD;
&#xD;
          8. Inability to attend daily for 10 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sabine Hazan, MD</last_name>
    <role>Study Director</role>
    <affiliation>ProgenaBiome</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Thomas Borody, MD</last_name>
    <role>Study Director</role>
    <affiliation>Topelia Therpeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ProgenaBiome</name>
      <address>
        <city>Ventura</city>
        <state>California</state>
        <zip>93003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>October 26, 2021</last_update_submitted>
  <last_update_submitted_qc>October 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 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>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>Vitamins</mesh_term>
    <mesh_term>Ascorbic Acid</mesh_term>
    <mesh_term>Zinc</mesh_term>
    <mesh_term>Doxycycline</mesh_term>
    <mesh_term>Ivermectin</mesh_term>
    <mesh_term>Zinc Sulfate</mesh_term>
  </intervention_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/NCT04482686
org study id: PRG-049
nct id: NCT04482686
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
In this trial patients will be treated with either a combination of therapies to treat
      COVID-19 or a placebo. Treatment will last 10 days, and patients will be followed for 6
      months.
Patients in this trial will undergo treatment for 10 days with either a combination of
      therapies or placebo. They will then be followed for an additional 20 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Time to Non-Infectivity by RT-PCR
time frame: 6 months
description: Time to negative RT-PRC result indicating that patient is no longer infective
measure: Time to Symptom progression in days as measured by NEWS scoring system (National Early Warning Score)
time frame: 6 months
description: Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.
measure: Time to Symptom improvement as measured by NEWS scoring system (National Early Warning Score)
time frame: 6 months
description: Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.
measure: Efficacy of Treatment as measured by Titer
time frame: 6 months
description: Patients will have serum stored for titer testing to compare antibody levels over time
measure: Efficacy of Treatment as measured by RT-PCR
time frame: 10 days
description: Number of patients testing negative for SARS-CoV-2 by RT-PCR after 10 days of treatment
measure: Safety of Treatment as Measured by D-Dimer
time frame: 6 Months
description: Blood D-Dimer levels
measure: Safety of Treatment as Measured by Pro-Calcitonin
time frame: 6 Months
description: Blood Pro-Calcitonin levels
measure: Safety of Treatment as Measured by C-Reactive Protein
time frame: 6 Months
description: Blood CRP levels
measure: Safety of Treatment as Measured by Ferritin
time frame: 6 Months
description: Blood ferritin levels
measure: Safety of Treatment as Measured by Liver Enzymes
time frame: 6 Months
description: Blood enzyme levels
measure: Safety of Treatment as Measured by Complete Blood Count
time frame: 6 Months
description: CBC
measure: Safety of Treatment as Measured by Electrolyte Levels
time frame: 6 Months
description: Blood electrolytes
measure: Safety of Treatment as Measured by Treatment Related Adverse Events
time frame: 6 months
description: Presence or absence of Grade 3 or high treatment related adverse events
arm group label: Active Arm
arm group type: Experimental
description: Patients will be treated with a combination of Ivermectin, Doxycycline, Zinc, Vitamin D3 and Vitamin C
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo and Vitamin D3, Vitamin C, and Zinc
intervention type: Drug
intervention name: Ivermectin
description: Treatment days 1, 4, and 8
arm group label: Active Arm
other name: Soolantra, Stromectol, Sklice
intervention type: Drug
intervention name: Doxycycline Hcl
description: 10 day treatment
arm group label: Active Arm
other name: Doxy-100, Monodox, Oracea, Targadox, Acticlate, Morgidox, Avidoxy, Doryx MPC, Mondoxyne NL, Dory
intervention type: Dietary Supplement
intervention name: Zinc
description: 10 Day treatment
arm group label: Active Arm
arm group label: Placebo
other name: Zinc sulphate
intervention type: Dietary Supplement
intervention name: Vitamin D3
description: 10 day treatment
arm group label: Active Arm
arm group label: Placebo
other name: cholecalciferol-D3
intervention type: Dietary Supplement
intervention name: Vitamin C
description: 10 day treatment
arm group label: Active Arm
arm group label: Placebo
other name: L-ascorbic acid
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sabine Hazan, MD
role: Study Director
affiliation: ProgenaBiome
last name: Thomas Borody, MD
role: Study Director
affiliation: Topelia Therpeutics
facility: 
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Severe Acute Respiratory Syndrome
mesh term: Vitamin D
mesh term: Cholecalciferol
mesh term: Vitamins
mesh term: Ascorbic Acid
mesh term: Zinc
mesh term: Doxycycline
mesh term: Ivermectin
mesh term: Zinc Sulfate
sharing ipd: No