<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/NCT03820414</url>
  </required_header>
  <id_info>
    <org_study_id>CRV-101-100</org_study_id>
    <nct_id>NCT03820414</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, and Immunogenicity of CRV-101 in Healthy Adult Subjects</brief_title>
  <official_title>A Phase 1, Randomized, Placebo-Controlled, Observer-Blind, Antigen Dose-Escalation and Adjuvant Dose-Ranging Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of CRV-101 in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Curevo Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Access to Advanced Health Institute (AAHI)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mogam Biotechnology Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Green Cross Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Curevo Inc</source>
  <oversight_info>
    <has_dmc>No</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>
      The purpose of this clinical trial is to evaluate the safety, tolerability, and&#xD;
      immunogenicity of vaccine candidate CRV-101, investigational vaccine in healthy adult&#xD;
      subjects in the United States.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 3, 2019</start_date>
  <completion_date type="Actual">April 30, 2020</completion_date>
  <primary_completion_date type="Actual">April 4, 2020</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>Sequential Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The number of subjects experiencing solicited local injection site reactions within 7 days following each study injection.</measure>
    <time_frame>7 Days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The number of subjects experiencing solicited systemic reactions within 7 days following each study injection.</measure>
    <time_frame>7 Days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The number of subjects spontaneously reporting unsolicited adverse events from Day 0 through 28 days after the last injection.</measure>
    <time_frame>28 Days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The number of medically-attended adverse events considered related to any of the study injections reported at any point during the study period events and potential immune-mediated medical conditions considered related to any of the study injections</measure>
    <time_frame>421 Days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The frequencies of vaccine protein-specific T cells elicited by the CRV101 study vaccine at specified time points.</measure>
    <time_frame>Day 0, 7, 28, 56, 63, 84, 196, and 365</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The levels of vaccine protein-specific antibodies elicited by the CRV101 study vaccine at specified time points</measure>
    <time_frame>Day 0, 7, 28, 56, 63, 84, 196, and 365</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Herpes Zoster</condition>
  <condition>Varicella Zoster</condition>
  <arm_group>
    <arm_group_label>CRV101 Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive 2 doses of the candidate CRV-101 formulation 1, administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CRV 101 Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive 2 doses of the candidate CRV-101 formulation 2, administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CRV 101 Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive 2 doses of the candidate CRV-101 formulation 3, administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CRV 101 Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive 2 doses of the candidate CRV-101 formulation 4, administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects received 2 doses of placebo (saline solution), administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CRV 101</intervention_name>
    <description>(Different formulations)</description>
    <arm_group_label>CRV 101 Group 2</arm_group_label>
    <arm_group_label>CRV 101 Group 3</arm_group_label>
    <arm_group_label>CRV 101 Group 4</arm_group_label>
    <arm_group_label>CRV101 Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>2 doses administered IM in deltoid region of non-dominant arm</description>
    <arm_group_label>Control Group</arm_group_label>
    <other_name>Saline injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and non-pregnant females ≥ 18 to &lt; 50 years of age at the time of enrollment.&#xD;
&#xD;
          2. In good general health as confirmed by a medical history and physical exam, vital&#xD;
             signs*, and screening laboratories conducted no more than 30 days prior to study&#xD;
             injection administration.&#xD;
&#xD;
             *Oral Temperature &lt;38°C, respiratory rate &lt; 17 breaths pm, heart rate ≤100 bpm and &gt;54&#xD;
             bpm, systolic blood pressure ≤150 mmHg and &gt;89 mmHg, diastolic blood pressure ≤95&#xD;
             mmHg.&#xD;
&#xD;
             NOTE: Athletically trained subjects with a heart rate ≥40 may be enrolled at the&#xD;
             discretion of the principal investigator or designated licensed clinical investigator&#xD;
             and reasoning must be documented.&#xD;
&#xD;
          3. Screening laboratory values must be within normal range or not clinically significant&#xD;
             as determined by the PI and approved by the Medical Monitor: sodium, potassium, BUN,&#xD;
             ALT, AST, total bilirubin, alkaline phosphatase, creatinine, random glucose, WBC with&#xD;
             differential, hemoglobin, and platelet count.&#xD;
&#xD;
          4. Negative HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus&#xD;
             (HCV) antibody.&#xD;
&#xD;
          5. Normal urinalysis or if abnormal determined to be not clinically significant by the PI&#xD;
             and the Medical Monitor (trace protein is acceptable without medical monitor&#xD;
             approval).&#xD;
&#xD;
          6. Urine test result for recreational drugs/drugs of abuse that in the opinion of the PI&#xD;
             would not be a concern for subject's safety, or ability to reliably attend visits, and&#xD;
             perform required protocol procedures. If urine drug test is positive, reasoning for&#xD;
             inclusion must be documented.&#xD;
&#xD;
          7. Females of childbearing potential* must have a negative serum pregnancy test at&#xD;
             screening and a negative urine pregnancy test on the day of each study vaccination&#xD;
             (prior to vaccination), must not be breast-feeding, and women in sexual relationships&#xD;
             with men must agree to practice acceptable contraception** for the 30-day period&#xD;
             before Day 0 through 90 days after the last study injection. These precautions are&#xD;
             necessary due to unknown effects that CRV-101 might cause in a fetus or newborn&#xD;
             infant.&#xD;
&#xD;
             *Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy or successful&#xD;
             Essure® placement (permanent, non-surgical, non-hormonal sterilization) with&#xD;
             documented radiological confirmation test at least 90 days after the procedure, and&#xD;
             still menstruating or &lt; 1 year of the last menses if menopausal). Post-menopausal&#xD;
             defined as at least 12 months spontaneous amenorrhea and confirmed with FSH &gt; 40&#xD;
             mIU/ml.&#xD;
&#xD;
             **Includes, but is not limited to, sexual abstinence, monogamous relationship with&#xD;
             vasectomized partner who has been vasectomized for 6 months or more prior to the&#xD;
             subject receiving study product, barrier methods such as condoms or diaphragms with&#xD;
             spermicide or foam, effective intrauterine devices, NuvaRing ®, and licensed hormonal&#xD;
             methods such as implants, injectables or oral contraceptives (&quot;the pill&quot;).&#xD;
&#xD;
          8. Exposure to VZV as documented by one of the following: subject reported clinical&#xD;
             history of chickenpox, previous vaccination against VZV with Varivax® (or other&#xD;
             low-titer live-attenuated varicella vaccine), or positive serology test for VZV.&#xD;
&#xD;
          9. Must be able to understand informed consent in English and capable of completing a&#xD;
             study diary card in English.&#xD;
&#xD;
         10. Must provide informed consent prior to any screening procedures performed, be able and&#xD;
             willing to make all study visits, be reachable by telephone or personal contact by the&#xD;
             study site personnel, and have a permanent address.&#xD;
&#xD;
         11. Willing to abstain from donating whole blood or blood derivatives until after Day 365&#xD;
             visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of chickenpox or herpes zoster in the past 3 years.&#xD;
&#xD;
          2. Immunization with a vaccine against herpes zoster (Zostavax® or Shingrix®).&#xD;
&#xD;
          3. Participation in another experimental protocol with last receipt of any device,&#xD;
             vaccine, or other immunomodulator investigational products within the past 180 days of&#xD;
             enrollment, or last receipt of non-device, non-vaccine, non-immunomodulator&#xD;
             investigational products with in the last 90 days of enrollment or 5 half-lives&#xD;
             whichever is greater, or planned participation in any other investigational study&#xD;
             during the study period.&#xD;
&#xD;
          4. Chronic administration (defined as more than 14 days in total) of immunosuppressants&#xD;
             or other immune-modifying drugs (e.g. oral or injected steroids, such as prednisone;&#xD;
             high dose inhaled steroids; biologics (e.g. TNF inhibitor, or other cytokine&#xD;
             inhibitors) or cytotoxic therapies, such as chemotherapy drugs or radiation) within&#xD;
             180 days prior to enrollment and during the study through Day 365 visit. For&#xD;
             corticosteroids, this will mean prednisone ≥ 0.5 mg/kg/day, or equivalent. Low dose&#xD;
             inhaled and topical steroids are allowed.&#xD;
&#xD;
          5. Received a blood transfusion or immunoglobulin within past 90 days of enrollment.&#xD;
&#xD;
          6. Donated blood products (platelets, whole blood, plasma, etc.) within past 60 days of&#xD;
             enrollment.&#xD;
&#xD;
          7. Received any vaccine within past 30 days prior to enrollment and no planned&#xD;
             immunizations while on study with the exception of seasonal influenza vaccine which&#xD;
             must not be given until 30 days after the last study injection and the Day 84&#xD;
             immunology blood has been drawn and a 30 day window prior to each immunology blood&#xD;
             draw (Day 196, 365).&#xD;
&#xD;
          8. History of autoimmune disease or other causes of immunosuppressive states.&#xD;
&#xD;
          9. History of any acute or chronic illness (including cardiovascular, pulmonary,&#xD;
             neurological, hepatic, rheumatic, hematological, metabolic or renal disorders,&#xD;
             controlled hypertension), or use of medication that, in the opinion of the Principal&#xD;
             Investigator, may interfere with the evaluation of the safety or immunogenicity of the&#xD;
             vaccine.&#xD;
&#xD;
         10. Rash, tattoos, or any other dermatological condition that could adversely affect the&#xD;
             vaccine injection site or interfere with its evaluation.&#xD;
&#xD;
         11. BMI that poses a health risk in the opinion of the Principal Investigator.&#xD;
&#xD;
         12. Hypertension (systolic &gt;150 or diastolic &gt;95).&#xD;
&#xD;
         13. History of significant psychiatric illness (including past history of suicidal&#xD;
             ideation or attempt) with or without current use of medication.&#xD;
&#xD;
         14. Known or suspected alcohol or drug abuse within the past 5 years.&#xD;
&#xD;
         15. Chronic smoker (&gt; 20 pack years).&#xD;
&#xD;
         16. Subjects with a history of previous anaphylaxis or severe allergic reaction to&#xD;
             vaccines or unknown allergens.&#xD;
&#xD;
         17. Subjects who are unlikely to cooperate with the requirements of the study protocol or&#xD;
             who are likely to be unreliable in attending study visits or other reason that the&#xD;
             Principal Investigator determines that the subject will not be a good candidate to&#xD;
             participate in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John E Ervin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Center for Pharmaceutical Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Corey Casper, MD</last_name>
    <role>Study Director</role>
    <affiliation>Access to Advanced Health Institute (AAHI)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lisa Shelton</last_name>
    <role>Study Chair</role>
    <affiliation>Curevo Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Center for Pharmaceutical Research</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.cdc.gov/shingles/hcp/clinical-overview.html</url>
    <description>Centers for Disease Control and Prevention: Shingles (Herpes Zoster): Clinical Overview</description>
  </link>
  <reference>
    <citation>Cohen JI. Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63. doi: 10.1056/NEJMcp1302674.</citation>
    <PMID>23863052</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>February 10, 2021</last_update_submitted>
  <last_update_submitted_qc>February 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>VZV, Vaccine, Shingles</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Herpes Zoster</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/NCT03820414
org study id: CRV-101-100
nct id: NCT03820414
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this clinical trial is to evaluate the safety, tolerability, and
      immunogenicity of vaccine candidate CRV-101, investigational vaccine in healthy adult
      subjects in the United States.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The number of subjects experiencing solicited local injection site reactions within 7 days following each study injection.
time frame: 7 Days
measure: The number of subjects experiencing solicited systemic reactions within 7 days following each study injection.
time frame: 7 Days
measure: The number of subjects spontaneously reporting unsolicited adverse events from Day 0 through 28 days after the last injection.
time frame: 28 Days
measure: The number of medically-attended adverse events considered related to any of the study injections reported at any point during the study period events and potential immune-mediated medical conditions considered related to any of the study injections
time frame: 421 Days
measure: The frequencies of vaccine protein-specific T cells elicited by the CRV101 study vaccine at specified time points.
time frame: Day 0, 7, 28, 56, 63, 84, 196, and 365
measure: The levels of vaccine protein-specific antibodies elicited by the CRV101 study vaccine at specified time points
time frame: Day 0, 7, 28, 56, 63, 84, 196, and 365
arm group label: CRV101 Group 1
arm group type: Experimental
description: Subjects receive 2 doses of the candidate CRV-101 formulation 1, administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.
arm group label: CRV 101 Group 2
arm group type: Experimental
description: Subjects receive 2 doses of the candidate CRV-101 formulation 2, administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.
arm group label: CRV 101 Group 3
arm group type: Experimental
description: Subjects receive 2 doses of the candidate CRV-101 formulation 3, administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.
arm group label: CRV 101 Group 4
arm group type: Experimental
description: Subjects receive 2 doses of the candidate CRV-101 formulation 4, administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.
arm group label: Control Group
arm group type: Placebo Comparator
description: Subjects received 2 doses of placebo (saline solution), administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 2 Month schedule.
intervention type: Biological
intervention name: CRV 101
description: (Different formulations)
arm group label: CRV 101 Group 2
arm group label: CRV 101 Group 3
arm group label: CRV 101 Group 4
arm group label: CRV101 Group 1
intervention type: Biological
intervention name: Placebo
description: 2 doses administered IM in deltoid region of non-dominant arm
arm group label: Control Group
other name: Saline injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: John E Ervin, MD
role: Principal Investigator
affiliation: The Center for Pharmaceutical Research
last name: Corey Casper, MD
role: Study Director
affiliation: Access to Advanced Health Institute (AAHI)
last name: Lisa Shelton
role: Study Chair
affiliation: Curevo Inc
facility: 
country: United States
url: https://www.cdc.gov/shingles/hcp/clinical-overview.html
description: Centers for Disease Control and Prevention: Shingles (Herpes Zoster): Clinical Overview
citation: Cohen JI. Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63. doi: 10.1056/NEJMcp1302674.
PMID: 23863052
responsible party type: Sponsor
mesh term: Herpes Zoster
sharing ipd: No