Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Novel Types 1 and 3 Oral Poliomyelitis Vaccines

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04529538
Recruitment Status : Recruiting
First Posted : August 27, 2020
Last Update Posted : August 30, 2021
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
Centers for Disease Control and Prevention
Viroclinics Biosciences B.V.
The Emmes Company, LLC
Information provided by (Responsible Party):
PATH

Tracking Information
First Submitted Date  ICMJE August 24, 2020
First Posted Date  ICMJE August 27, 2020
Last Update Posted Date August 30, 2021
Actual Study Start Date  ICMJE March 26, 2021
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2020)
  • Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: From Day 1 to end of study, up to 169 days ]
    A serious adverse event is any adverse event that results in any of the following outcomes:
    • Death
    • Is life-threatening
    • Requires inpatient hospitalization or prolongation of existing hospitalization
    • Results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
    • Congenital anomaly or birth defect
    • Important medical event that may not result in one of the above outcomes but may jeopardize the health of the study participant and/or require medical or surgical intervention to prevent one of the outcomes listed above
  • Number of Participants with Solicited Adverse Events (AEs) 7 Days after Each Dose of Study Vaccine [ Time Frame: From vaccination to 7 days post vaccination (Day 8 and Day 36) ]
    Solicited AEs are pre-specific AEs that are common or known to be associated with vaccination that are actively monitored as potential indicators of vaccine reactogenicity. Solicited AEs for this study are:
    • Fever (oral temperature ≥ 38.0°C or 100.4°F)
    • Chills
    • Fatigue
    • Headache
    • Muscle aches/myalgias
    • Joint aches/arthralgias
    • Nausea
    • Vomiting
    • Abdominal pain
    • Diarrhea
  • Number of Participants with Unsolicited Adverse Events (AEs) up to 28 days Post Vaccination [ Time Frame: From vaccination to 28 days post vaccination ]
    Unsolicited AEs are any AEs reported spontaneously by the participant, observed by the study personnel during study visits or those identified during review of medical records or source documents. In the absence of a diagnosis, abnormal physical examination findings or abnormal clinical safety laboratory test results that are assessed by the investigator to be clinically significant will be reported as an AE.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2020)
  • Median Anti-polio Serum Neutralizing Antibody Titers for Poliomyelitis Type 1 at Baseline and Post-vaccination among Participants with a Vaccine History of IPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Median Anti-polio Serum Neutralizing Antibody Titers for Poliomyelitis Type 1 at Baseline and Post-vaccination among Participants with a Vaccine History of OPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Median Anti-polio Serum Neutralizing Antibody Titers for Poliomyelitis Type 3 at Baseline and Post-vaccination among Participants with a Vaccine History of IPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Median Anti-polio Serum Neutralizing Antibody Titers for Poliomyelitis Type 3 at Baseline and Post-vaccination among Participants with a Vaccine History of OPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Geometric Mean Titer of Anti-polio Serum Neutralizing Antibody Titer for Poliomyelitis Type 1 at Baseline and Post-vaccination among Participants with a Vaccine History of IPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Geometric Mean Titer of Anti-polio Serum Neutralizing Antibody Titer for Poliomyelitis Type 1 at Baseline and Post-vaccination among Participants with a Vaccine History of OPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Geometric Mean Titer of Anti-polio Serum Neutralizing Antibody Titer for Poliomyelitis Type 3 at Baseline and Post-vaccination among Participants with a Vaccine History of IPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Geometric Mean Titer of Anti-polio Serum Neutralizing Antibody Titer for Poliomyelitis Type 3 at Baseline and Post-vaccination among Participants with a Vaccine History of OPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Geometric Mean Titer Ratio of Anti-polio Serum Neutralizing Antibody Titer for Poliomyelitis Type 1 among Participants with a Vaccine History of IPV [ Time Frame: 28 days post-vaccination ]
  • Geometric Mean Titer Ratio of Anti-polio Serum Neutralizing Antibody Titer for Poliomyelitis Type 1 among Participants with a Vaccine History of OPV [ Time Frame: 28 days post-vaccination ]
  • Geometric Mean Titer Ratio of Anti-polio Serum Neutralizing Antibody Titer for Poliomyelitis Type 3 among Participants with a Vaccine History of IPV [ Time Frame: 28 days post-vaccination ]
  • Geometric Mean Titer Ratio of Anti-polio Serum Neutralizing Antibody Titer for Poliomyelitis Type 3 among Participants with a Vaccine History of OPV [ Time Frame: 28 days post-vaccination ]
  • Percentage of Participants with Any-Fold Rise, 2-fold rise and 4-fold rise in Anti-polio Serum Neutralizing Antibody Titers for Poliomyelitis Type 1 among Participants with a Vaccine History of IPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Percentage of Participants with Any-Fold Rise, 2-fold rise and 4-fold rise in Anti-polio Serum Neutralizing Antibody Titers for Poliomyelitis Type 1 among Participants with a Vaccine History of OPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Percentage of Participants with Any-Fold Rise, 2-fold rise and 4-fold rise in Anti-polio Serum Neutralizing Antibody Titers for Poliomyelitis Type 3 among Participants with a Vaccine History of IPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Percentage of Participants with Any-Fold Rise, 2-fold rise and 4-fold rise in Anti-polio Serum Neutralizing Antibody Titers for Poliomyelitis Type 3 among Participants with a Vaccine History of OPV [ Time Frame: Baseline and 28 days post-vaccination ]
  • Time to Cessation of Fecal Shedding of the Vaccine Virus [ Time Frame: Up to 169 days ]
    The presence of the vaccine virus in stool samples will be assessed using polymerase chain reaction (PCR). Time to cessation of shedding is defined as the time between vaccination and the last PCR-positive stool prior to 2 consecutive PCR-negative stools (with a minimum 24-hour interval between the 2 negative stools).
  • Percentage of Participants Shedding Vaccine Virus at each Post-vaccination Stool Collection in Participants with IPV Vaccination History [ Time Frame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57 ]
    Presence of the vaccine virus in stool samples will be assessed by polymerase chain reaction (PCR).
  • Amount of Vaccine Virus in each Stool Sample Positive for Virus in Participants with IPV Vaccination History [ Time Frame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57 ]
    Samples positive for vaccine virus in stool as detected by PCR will be quantified using a cell culture infectious dose assay.
  • Shedding Index of Vaccine Virus Shedding in Stool in Participants with IPV Vaccination History [ Time Frame: Days 8, 15, 22, and 29 ]
    The Shedding Index Endpoint (SIE) will be computed as the mean of the log10 cell culture infectious dose 50% (CCID50) per gram from nominal collection days 7, 14, 21, and 28 post-dose (i.e., study days 8, 15, 22, and 29 following the first dose).
  • Area Under the Curve (AUC) of Vaccine Virus Shed in Stool in Participants with an IPV Vaccination History [ Time Frame: Day 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Novel Types 1 and 3 Oral Poliomyelitis Vaccines
Official Title  ICMJE A First-in-human, Phase 1, Randomized, Observer-blind, Controlled Study to Assess the Safety and Immunogenicity of Novel Live Attenuated Type 1 and Type 3 Oral Poliomyelitis Vaccines in Healthy Adults
Brief Summary The purpose of this study is to assess the safety (primary objective) and immunogenicity (secondary objective) and fecal shedding of vaccine viruses (secondary objective) of two novel oral polio vaccines, nOPV1 and nOPV3, as compared to Sabin monovalent vaccine controls, in 230 healthy adults.
Detailed Description This multicenter trial is the first-in-human assessment of two novel oral polio vaccines for poliovirus type 1 and type 3. It will be an 8-arm, randomized, observer-blind, controlled trial, with Sabin monovalent vaccines serving as the control for each type. Two hundred and thirty healthy, adult participants will be recruited, 80 participants with an exclusive inactivated poliovirus vaccine (IPV) prior vaccination history and 150 participants with an oral poliomyelitis vaccine (OPV)-containing prior vaccination history.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
It will be an 8-arm, randomized, observer-blind, controlled trial
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Poliomyelitis
Intervention  ICMJE
  • Biological: Novel Oral Polio Vaccine Type 1 (nOPV1)
    Each 0.1 mL (2 drops) dose of vaccine contains approximately 10^6.5 CCID50.
  • Biological: Novel Oral Polio Vaccine Type 3 (nOPV3)
    Each 0.1 mL (2 drops) dose of vaccine contains approximately 10^6.5 CCID50.
  • Biological: Sabin Monovalent Oral Polio Vaccine Type 1 (mOPV1)
    The Sabin mOPV1 control vaccine contains ≥ 10^6.0 CCID50 per 0.1 mL (2 drops) dose.
  • Biological: Sabin Monovalent Oral Polio Vaccine Type 3 (mOPV3)
    the Sabin mOPV3 control vaccine contains ≥ 10^5.8 CCID50 per 0.1 mL (2 drops) dose.
    Other Name: Sabin monovalent oral polio vaccine type 3
Study Arms  ICMJE
  • Experimental: Group1: nOPV1 (IPV History)
    20 healthy adults fully vaccinated against polio exclusively by IPV will be administered 1 vaccination of novel OPV type 1 (nOPV1) containing 10^6.5 CCID50/dose.
    Intervention: Biological: Novel Oral Polio Vaccine Type 1 (nOPV1)
  • Active Comparator: Group 2: mOPV1 (IPV History)
    20 healthy adults fully vaccinated against polio exclusively by IPV will be administered 1 vaccination of mOPV1 containing 10^6.0 CCID50/dose.
    Intervention: Biological: Sabin Monovalent Oral Polio Vaccine Type 1 (mOPV1)
  • Experimental: Group 3: nOPV1 (OPV History)
    50 healthy adults fully vaccinated against polio by OPV will be administered 2 vaccinations of nOPV1 containing 10^6.5 CCID50/dose, given 28 days apart.
    Intervention: Biological: Novel Oral Polio Vaccine Type 1 (nOPV1)
  • Active Comparator: Group 4: mOPV1 (OPV History)
    25 healthy adults fully vaccinated against polio by OPV will be administered 2 doses of mOPV1containing ≥ 10^6.0 CCID50/dose, given 28 days apart
    Intervention: Biological: Sabin Monovalent Oral Polio Vaccine Type 1 (mOPV1)
  • Experimental: Group 5: nOPV3 (IPV History)
    20 healthy adults fully vaccinated against polio exclusively by IPV will be administered 1 vaccination of nOPV3 containing 10^6.5 CCID50/dose.
    Intervention: Biological: Novel Oral Polio Vaccine Type 3 (nOPV3)
  • Active Comparator: Group 6: mOPV3 (IPV History)
    20 healthy adults fully vaccination against polio by exclusively IPV will be administered 1 vaccination of mOPV3 containing ≥ 10^5.8 CCID50/dose.
    Intervention: Biological: Sabin Monovalent Oral Polio Vaccine Type 3 (mOPV3)
  • Experimental: Group 7: nOPV3 (OPV History)
    50 healthy adults fully vaccinated against polio by OPV will be administered 2 vaccinations of nOPV3 in a dose of 10^6.5 CCID50/dose, given 28 days apart.
    Intervention: Biological: Novel Oral Polio Vaccine Type 3 (nOPV3)
  • Active Comparator: Group 8: mOPV3 (OPV History)
    25 healthy adults fully vaccinated against polio by OPV will be administered 2 vaccinations of mOPV3 containing ≥ 10^5.8 CCID50/dose, given 28 days apart.
    Intervention: Biological: Sabin Monovalent Oral Polio Vaccine Type 3 (mOPV3)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 26, 2020)
230
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Males or females, from 18 to 45 years of age (inclusive) at the time of enrollment
  2. Healthy, as defined by the absence of any clinically significant medical conditions, either acute or chronic, as determined by medical history, physical examination, screening laboratory test results, and clinical assessment of the investigator
  3. Willing and able to provide written informed consent prior to performance of any study-specific procedure
  4. If female and of childbearing potential*, be not breastfeeding and not pregnant (based on a negative serum pregnancy test at screening and a negative urine pregnancy test during the 24 hours prior to any study vaccination), agreeing to have repeated pregnancy tests prior to any study vaccination, and having practiced adequate contraception** for 30 days prior to first study vaccination and willing to continue using adequate contraception consistently for at least 90 days after the last study vaccination and until cessation of vaccine virus shedding is confirmed

    • Females can be considered not of childbearing potential if they are with current bilateral tubal ligation, occlusion or removal, or post-total hysterectomy, or post-bilateral ovariectomy

      • Adequate contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label, for example:

        • Abstinence from penile-vaginal intercourse
        • Combined estrogen and progesterone oral contraceptives
        • Hormonal (e.g., progestogen) injections
        • Hormonal (e.g., etonogestrel or levonorgestrel) implants
        • Contraceptive vaginal ring
        • Percutaneous contraceptive patches
        • Intrauterine device
        • Intrauterine hormonal system
        • Male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository), and/or progesterone alone oral contraceptive
        • Monogamous relationship with vasectomized (180 days or more prior to enrollment) partner
  5. Resides in study area and is able and willing to adhere to all study restrictions and to all study visits and procedures (as evidenced by a signed informed consent form and assessment by the investigator)
  6. Agrees not to and has no plans to travel outside the United States until confirmation of cessation of vaccine virus shedding in stool at or after the Day 57 stool collection
  7. Able and willing to be contacted by telephone or text, and willing for study staff to leave telephone voice or electronic messages as needed
  8. Neutralizing antibody titer ≥ 1:8 for poliovirus type 1 (for participants in cohorts 1 and 2) and ≥ 1:8 for poliovirus type 3 (for participants in cohorts 3 and 4)
  9. For Cohorts 1 and 3 only: previously received at least 3 doses of IPV and with no history of receipt of OPV. For Cohorts 2 and 4 only: previously received a primary polio immunization series containing OPV

Exclusion Criteria:

  1. Have any condition (medical, psychiatric or behavioral) that, in the opinion of the investigator, would increase the participant's health risks in study participation or would increase the risk of not achieving the study's objectives (e.g., would compromise adherence to protocol requirements or interfere with planned safety and immunogenicity assessments)
  2. Receipt of polio vaccine within 12 months before the start of the study
  3. Having Crohn's disease or ulcerative colitis or having had major surgery of the gastrointestinal tract involving significant loss or resection of the bowel
  4. A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin)
  5. Any confirmed or suspected immunosuppressive or immunodeficiency condition (human immunodeficiency virus [HIV] infection, or total serum immunoglobulin A (IgA) or immunoglobulin G (IgG) level below the testing laboratory's lower limit of normal [LLN])
  6. Administration of any long-acting immune-modifying drugs (e.g., infliximab or rituximab) or the chronic administration (i.e., longer than 14 days) of immunosuppressant drugs (e.g., oral or systemic steroids) or other immune-modifying drugs within 6 months prior to the first vaccine dose or planned use during the study (inhaled and topical steroids are allowed whereas intra-articular and epidural injection/administration of steroids are not allowed)
  7. Will have household direct or close professional contact during the study with individuals expected to be immunosuppressed (due to underlying condition or treatments) or individuals who have not yet completed their primary infant polio immunization series (i.e., three doses)
  8. Will have household direct or close professional contact during the study with pregnant women
  9. Will have household direct or close professional (e.g., neonatal nurses) contact during the study with children less than 2 years of age or with individuals who are encopretic (i.e., infants/toddlers who are not yet toilet trained or other individuals, including adults, with fecal incontinence)
  10. Will have professional handling of food, catering, or food production activities during the study
  11. Reside in homes with septic tanks
  12. Acute illness or fever (body temperature measured orally ≥ 38°C or 100.4°F) at the time of study vaccine administration (once acute illness/fever is resolved, if appropriate, as per investigator assessment, participant may complete screening)
  13. Indications of drug abuse or excessive use of alcohol as deemed by the investigator to confound safety assessments or render the participant unable or unlikely to adhere to protocol requirements or provide accurate safety reports
  14. Participation in another investigational product (drug or vaccine) clinical trial within 30 days prior to entry in this study or receipt of any such investigational product other than the study vaccine within 30 days prior to the first administration of study vaccine, or planned use during the study period
  15. Administration of any vaccine other than the study vaccine or any intramuscular injection within 30 days prior to the first dose of study vaccine or planned administration within 30 days prior to or after any study vaccination
  16. Receipt of transfusion of any blood product or application of immunoglobulins within the 12 weeks prior to the first administration of study vaccine or planned use during the study period
  17. Hepatitis B or C virus infection
  18. Any hematological# or chemistry** parameter that is out of range of normal†† and is considered clinically significant by the investigator #Complete blood count (CBC), includes hemoglobin, hematocrit, white blood cell (WBC) count, neutrophil count, lymphocyte count, eosinophil count, and platelet count

    **Creatinine, alanine transaminase (ALT), total bilirubin

    ††Per the site clinical laboratory's reference ranges. All tests with out of range results must be repeated before any participant can be enrolled

  19. The following hematological or chemistry laboratory results will be considered exclusionary, irrespective of assessment of clinical significance:

Hemoglobin (Male) < 12.5 g/dL Hemoglobin (Female) < 11.0 g/dL Neutrophil count < 1,000 cells/mm3 Eosinophil count > 650 cells/mm3 Platelet count < 125,000 cells/mm3 Creatinine > 1.4 mg/dL ALT > 1.1 X Upper limit of normal (ULN) ††

††Per the site clinical laboratory's reference ranges

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Renee J Holt, JD, MPH 206-491-1977 rholt@path.org
Contact: Rahsan Erdem, MD 202-540-4546 rerdem@path.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04529538
Other Study ID Numbers  ICMJE CVIA 076
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PATH
Study Sponsor  ICMJE PATH
Collaborators  ICMJE
  • Bill and Melinda Gates Foundation
  • Centers for Disease Control and Prevention
  • Viroclinics Biosciences B.V.
  • The Emmes Company, LLC
Investigators  ICMJE
Principal Investigator: Elizabeth R Colgate, PhD University of Vermont
Principal Investigator: Arlene Sena, MD University of North Carolina
Principal Investigator: Peter Wright, MD Dartmouth-Hitchcock Medical Center
PRS Account PATH
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP