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CompletedNCT04529538Updated Nov 20, 2024Results posted

Study of Novel Types 1 and 3 Oral Poliomyelitis Vaccines

A Phase 1 interventional study of Novel Oral Polio Vaccine Type 1 (nOPV1) and Novel Oral Polio Vaccine Type 3 (nOPV3) in Poliomyelitis, sponsored by PATH. Completed at 4 sites in United States. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-11-20.

Sponsored by PATH · Phase 1, Interventional, and Prevention

Phase
Phase 1
Study type
Interventional
Enrollment
226
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
All
01

Study summary

The purpose of this study is to assess the safety (primary objective), the ability to trigger the production of antibodies (immunogenicity; a secondary objective) and presence of vaccine virus in the stool (fecal shedding; a secondary objective) of two novel oral polio vaccines (nOPV), novel oral poliomyelitis vaccine type 1 (nOPV1) and novel oral poliomyelitis vaccine type 3 (nOPV3), as compared to Sabin strain monovalent oral poliomyelitis vaccine (mOPV) controls, in healthy adults.

Read the 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 a 4-cohort, 8-arm, randomized, observer-blind, controlled trial, with Sabin monovalent vaccines serving as the control for each type:

Cohort 1: Healthy adults with an exclusive inactivated poliovirus vaccine (IPV) prior vaccination history will be randomized in a 1:1 ratio and allocated to receive nOPV1 (Group 1) or mOPV1 (Group 2).

Cohort 2: Healthy adults with an OPV-containing prior vaccination history will be randomized in a 2:1 ratio and allocated to receive two doses of nOPV1 (Group 3) or mOPV1 (Group 4), respectively;

Cohort 3: Healthy adults with an exclusive IPV prior vaccination history will be randomized in a 1:1 ratio and allocated to receive nOPV3 (Group 5) or mOPV3 (Group 6);

Cohort 4: Healthy adults with an OPV-containing prior vaccination history will be randomized in a 2:1 ratio to study groups 3 and 4 and allocated to receive two doses of nOPV3 (Group 7) or mOPV3 (Group 8), respectively.

02

Conditions studied

  • Poliomyelitis

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Keywords

  • Vaccine tolerability
  • Vaccine reactogenicity
  • Vaccine viral shedding
  • Vaccine immunogenicity
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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 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 [ICF] and assessment by the investigator)
  6. Agrees not to and has no plans to travel outside the United States (US) until confirmation of cessation of vaccine virus shedding in stool at or after the study 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

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 intraarticular 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 (except seasonal inactivated influenza and COVID-19 vaccines which are prohibited for only 14 days prior to or following each study vaccination) 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 that are regarded as clinically significant by the clinician must be repeated and determined to be not clinically significant 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/mm\^3
    • Eosinophil count > 650 cells/mm\^3
    • Platelet count \< 125,000 cells/mm\^3
    • Creatinine > 1.4 mg/dL
    • ALT > 1.1 X upper limit of normal (ULN) (per the site clinical laboratory's reference ranges)
04

Study design

Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
226 participants (actual)

Study arms

  • Experimental
    Group1: nOPV1 (IPV History)

    Healthy adults fully vaccinated against polio exclusively by IPV were administered 1 vaccination of novel OPV type 1 (nOPV1) containing 10\^6.5 cell culture infectious dose 50% (CCID50) on Day 1.

    Biological: Novel Oral Polio Vaccine Type 1 (nOPV1)

  • Active comparator
    Group 2: mOPV1 (IPV History)

    Healthy adults fully vaccinated against polio exclusively by IPV were administered 1 vaccination of mOPV1 containing 10\^6.0 CCID50 on Day 1.

    Biological: Sabin Monovalent Oral Polio Vaccine Type 1 (mOPV1)

  • Experimental
    Group 3: nOPV1 (OPV History)

    Healthy adults fully vaccinated against polio with an OPV-containing vaccine history were administered 2 vaccinations of nOPV1 containing 10\^6.5 CCID50/dose, given 28 days apart.

    Biological: Novel Oral Polio Vaccine Type 1 (nOPV1)

  • Active comparator
    Group 4: mOPV1 (OPV History)

    Healthy adults fully vaccinated against polio with an OPV-containing vaccine history were administered 2 doses of mOPV1 containing ≥ 10\^6.0 CCID50/dose, given 28 days apart.

    Biological: Sabin Monovalent Oral Polio Vaccine Type 1 (mOPV1)

  • Experimental
    Group 5: nOPV3 (IPV History)

    Healthy adults fully vaccinated against polio exclusively by IPV were administered 1 vaccination of nOPV3 containing 10\^6.5 CCID50 on Day 1.

    Biological: Novel Oral Polio Vaccine Type 3 (nOPV3)

  • Active comparator
    Group 6: mOPV3 (IPV History)

    Healthy adults fully vaccinated against polio by exclusively IPV were administered 1 vaccination of mOPV3 containing ≥ 10\^5.8 CCID50 on Day 1.

    Biological: Sabin Monovalent Oral Polio Vaccine Type 3 (mOPV3)

  • Experimental
    Group 7: nOPV3 (OPV History)

    Healthy adults fully vaccinated against polio with an OPV-containing vaccine history were administered 2 vaccinations of nOPV3 in a dose of 10\^6.5 CCID50/dose, given 28 days apart.

    Biological: Novel Oral Polio Vaccine Type 3 (nOPV3)

  • Active comparator
    Group 8: mOPV3 (OPV History)

    Healthy adults fully vaccinated against polio with an OPV-containing vaccine history were administered 2 vaccinations of mOPV3 containing ≥ 10\^5.8 CCID50/dose, given 28 days apart.

    Biological: Sabin Monovalent Oral Polio Vaccine Type 3 (mOPV3)

Interventions

  • BiologicalNovel Oral Polio Vaccine Type 1 (nOPV1)

    Each 0.1 mL (2 drops) dose of vaccine contains approximately 10\^6.5 CCID50.

  • BiologicalNovel Oral Polio Vaccine Type 3 (nOPV3)

    Each 0.1 mL (2 drops) dose of vaccine contains approximately 10\^6.5 CCID50.

  • BiologicalSabin Monovalent Oral Polio Vaccine Type 1 (mOPV1)

    The Sabin mOPV1 control vaccine contains ≥ 10\^6.0 CCID50 per 0.1 mL (2 drops) dose.

  • BiologicalSabin Monovalent Oral Polio Vaccine Type 3 (mOPV3)

    the Sabin mOPV3 control vaccine contains ≥ 10\^5.8 CCID50 per 0.1 mL (2 drops) dose.

    Also known as: Sabin monovalent oral polio vaccine type 3

05

What researchers measure

Primary outcomes

  1. Number of Participants With Serious Adverse Events (SAEs)

    A serious adverse event is any adverse event that resulted in any of the following outcomes: * Death * Was life-threatening * Required inpatient hospitalization or prolongation of existing hospitalization * Resulted 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

    Time frame: From Day 1 to end of study, up to 169 days

  2. Number of Participants With Solicited Adverse Events (AEs) 7 Days After First Dose of Study Vaccine

    Solicited AEs are pre-specified 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 included: * Fever (oral temperature ≥ 38.0°C or 100.4°F) * Chills * Fatigue * Headache * Muscle aches/myalgias * Joint aches/arthralgias * Nausea * Vomiting * Abdominal pain * Diarrhea

    Time frame: From vaccination to 7 days post vaccination (Days 1-7)

  3. Number of Participants With Solicited Adverse Events 7 Days After Second Dose of Study Vaccine

    Solicited AEs are pre-specified 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 included: * Fever (oral temperature ≥ 38.0°C or 100.4°F) * Chills * Fatigue * Headache * Muscle aches/myalgias * Joint aches/arthralgias * Nausea * Vomiting * Abdominal pain * Diarrhea

    Time frame: From Day 29 to Day 35

  4. Number of Participants With Unsolicited Adverse Events (AEs) up 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 were reported as an AE.

    Time frame: From vaccination to 28 days post vaccination (Day 1-28 for 1st vaccination and Day 29-56 for the 2nd vaccination)

Secondary outcomes

  1. Median Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV

    Blood samples collected from participants for type-specific poliovirus neutralizing antibodies were analyzed at the Polio and Picornavirus Laboratory Branch at the United States Centers for Disease Control and Prevention (CDC). For all immunogenicity endpoints, data are presented separately by: * Prior vaccination history (exclusively IPV vs OPV), and * Type-specific poliovirus vaccine received (type 1 vs type 3).

    Time frame: Baseline and Day 29 (28 days post-vaccination)

  2. Median Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV

    Time frame: Baseline, Day 29 (28 days post-vaccination) and Day 57 (28 days after 2nd vaccination)

  3. Median Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV

    Time frame: Baseline and Day 29 (28 days post-vaccination)

  4. Median Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV

    Time frame: Baseline, Day 29 (28 days after the 1st vaccination) and Day 57 (28 days after 2nd vaccination)

  5. Geometric Mean Titer (GMT) of Anti-poliovirus Type 1 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV

    GMT and 95% confidence intervals are maximum likelihood estimates incorporating left and right censoring at the lower limit of quantitation (LLOQ) and ULOQ, respectively.

    Time frame: Baseline and Day 29 (28 days post-vaccination)

  6. Geometric Mean Titer of Anti-poliovirus Type 1 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV

    Time frame: Baseline, Day 29 (28 days after 1st vaccination) and Day 57 (28 days after 2nd vaccination)

  7. Geometric Mean Titer of Anti-poliovirus Type 3 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV

    Time frame: Baseline and Day 29 (28 days post-vaccination)

  8. Geometric Mean Titer of Anti-poliovirus Type 3 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV

    Time frame: Baseline, Day 29 (28 days after 1st vaccination) and Day 57 (28 days after 2nd vaccination)

  9. Percentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Vaccination Among Participants With a Vaccine History of IPV

    * Seroconversion (SCR) is defined as a minimum 4-fold increase in titer from Baseline (pre-vaccination) to 28 days post-vaccination among those participants with a 4-fold increase possible to observe, i.e., with a Baseline titer not greater than 8.5 log₂. * Minimum 2-fold-rise from Baseline to 28 days post-vaccination among those participants with a 2-fold increase possible to observe, i.e., with a Baseline titer not greater than 9.5 log₂. * Any fold-rise is defined as any increase in titer from Baseline to 28 days post-vaccination (log₂ neutralizing antibody titer post-dose minus Baseline \> 0), among those with an increase possible to observe, i.e., with a Baseline titer less than 10.5 log₂.

    Time frame: Baseline (pre-vaccination) and Day 29 (28 days post-vaccination)

  10. Percentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Each Vaccination Among Participants With a Vaccine History of OPV

    * Seroconversion (SCR) is defined as a minimum 4-fold increase in titer from Baseline (pre-vaccination) to 28 days post-vaccination among those participants with a 4-fold increase possible to observe, i.e., with a Baseline titer not greater than 8.5 log₂. * Minimum 2-fold-rise from Baseline to 28 days post-vaccination among those participants with a 2-fold increase possible to observe, i.e., with a Baseline titer not greater than 9.5 log₂. * Any fold-rise is defined as any increase in titer from Baseline to 28 days post-vaccination (log₂ neutralizing antibody titer post-dose minus Baseline \> 0), among those with an increase possible to observe, i.e., with a Baseline titer less than 10.5 log₂.

    Time frame: Baseline, Day 29 (28 days post-vaccination) and Day 57 (28 days after 2nd vaccination)

  11. Percentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Vaccination Among Participants With a Vaccine History of IPV

    * Seroconversion (SCR) is defined as a minimum 4-fold increase in titer from Baseline (pre-vaccination) to 28 days post-vaccination among those participants with a 4-fold increase possible to observe, i.e., with a Baseline titer not greater than 8.5 log₂. * Minimum 2-fold-rise from Baseline to 28 days post-vaccination among those participants with a 2-fold increase possible to observe, i.e., with a Baseline titer not greater than 9.5 log₂. * Any fold-rise is defined as any increase in titer from Baseline to 28 days post-vaccination (log₂ neutralizing antibody titer post-dose minus Baseline \> 0), among those with an increase possible to observe, i.e., with a Baseline titer less than 10.5 log₂.

    Time frame: Baseline and Day 29 (28 days post-vaccination)

  12. Percentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Each Vaccination Among Participants With a Vaccine History of OPV

    * Seroconversion (SCR) is defined as a minimum 4-fold increase in titer from Baseline (pre-vaccination) to 28 days post-vaccination among those participants with a 4-fold increase possible to observe, i.e., with a Baseline titer not greater than 8.5 log₂. * Minimum 2-fold-rise from Baseline to 28 days post-vaccination among those participants with a 2-fold increase possible to observe, i.e., with a Baseline titer not greater than 9.5 log₂. * Any fold-rise is defined as any increase in titer from Baseline to 28 days post-vaccination (log₂ neutralizing antibody titer post-dose minus Baseline \> 0), among those with an increase possible to observe, i.e., with a Baseline titer less than 10.5 log₂.

    Time frame: Baseline, Day 29 (28 days after 1st vaccination) and Day 57 (28 days after 2nd vaccination)

  13. Time to Cessation of Fecal Shedding of Vaccine Virus in Participants With IPV Vaccination History

    The presence of the vaccine virus in stool samples was 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). The time to cessation of fecal shedding of nOPV1 and nOPV3 in prior IPV recipients was estimated using Kaplan-Meier methodology with interval-censoring.

    Time frame: Up to Day 57

  14. Time to Cessation of Fecal Shedding of Vaccine Virus in Participants With OPV Vaccination History

    The presence of the vaccine virus in stool samples was 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). The time to cessation of fecal shedding of nOPV1 and nOPV3 in prior OPV recipients was evaluated separately after each dose, estimated using Kaplan-Meier methodology with interval-censoring.

    Time frame: From vaccination through 28 days after each vaccination

  15. Percentage of Participants Shedding Type 1 Vaccine Virus at Each Post-vaccination Stool Collection in Participants With IPV Vaccination History

    Presence of the vaccine virus in stool samples was assessed by polymerase chain reaction (PCR). This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

    Time frame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57

  16. Percentage of Participants Shedding Type 3 Vaccine Virus at Each Post-vaccination Stool Collection in Participants With IPV Vaccination History

    Presence of the vaccine virus in stool samples was assessed by polymerase chain reaction (PCR). This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

    Time frame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57

  17. Amount of Type 1 Vaccine Virus in Each Stool Sample Positive for Virus in Participants With IPV Vaccination History

    Samples positive for vaccine virus in stool as detected by PCR were quantified using a cell culture infectious dose assay. Participants who were PCR-positive for type 1 viral shedding but with log₁₀ CCID50 per gram ≤ LLOQ contributed a value equal to the LLOQ. This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

    Time frame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57

  18. Amount of Type 3 Vaccine Virus in Each Stool Sample Positive for Virus in Participants With IPV Vaccination History

    Samples positive for vaccine virus in stool as detected by PCR were quantified using a cell culture infectious dose assay. Participants who were PCR-positive for type 3 viral shedding but with log₁₀ CCID50 per gram ≤ LLOQ contributed a value equal to the LLOQ. This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

    Time frame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57

  19. Shedding Index of Vaccine Virus Shedding in Stool in Participants With IPV Vaccination History

    The Shedding Index Endpoint (SIE) was 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). Participants who were PCR-positive for type-specific viral shedding but with log₁₀ CCID50 per gram ≤ LLOQ contributed a value equal to the LLOQ. This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

    Time frame: Days 8, 15, 22, and 29

  20. Area Under the Curve From Vaccination to 28 Days After Vaccination (AUC₀-₂₈) of Vaccine Virus Shed in Stool in Participants With an IPV Vaccination History

    Area under the curve (AUC) was computed for each participant using CCID50 per gram data collected through Day 29 using the linear trapezoidal rule. Participants were assumed to be not shedding at time of vaccination (i.e. there was no stool collection on Day 1). Participants who were PCR-positive for type-specific viral shedding but with log₁₀ CCID50 per gram ≤ LLOQ contributed a value equal to the LLOQ. This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

    Time frame: Days 3, 5, 8, 10, 15, 22, and 29

06

Results

Posted Sep 25, 2024

Participant flow

Healthy volunteers were enrolled at four study sites in the United States. This study consisted of 4 cohorts, each with 2 groups of participants. Participants must have received either prior vaccination with at least 3 doses of inactivated poliovirus vaccine (IPV) with no history of receipt of oral poliomyelitis vaccine (OPV) (Cohorts 1 and 3) or previously received a primary polio immunization series containing OPV (Cohorts 2 and 4).

Participant flow — Overall Study
MilestoneGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
Started2123532720214021
Received 1st vaccination2020502519173519
Received 2nd vaccination004922003518
Completed1818492219173519
Not completed35451452
Withdrew: Lost to follow-up32101120
Withdrew: Not eligible at enrollment01210001
Withdrew: Withdrawal by subject01120230
Withdrew: Other01000000
Withdrew: Adverse event00010000
Withdrew: Protocol deviation00010000
Withdrew: Physician decision00000101

Outcome measures

PrimaryNumber of Participants With Serious Adverse Events (SAEs)

A serious adverse event is any adverse event that resulted in any of the following outcomes: * Death * Was life-threatening * Required inpatient hospitalization or prolongation of existing hospitalization * Resulted 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

Time frame:
From Day 1 to end of study, up to 169 days
Reported as:
Count of participants · Participants
Number of Participants With Serious Adverse Events (SAEs)
ParticipantsGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
Number of Participants With Serious Adverse Events (SAEs)00000000
PrimaryNumber of Participants With Solicited Adverse Events (AEs) 7 Days After First Dose of Study Vaccine

Solicited AEs are pre-specified 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 included: * Fever (oral temperature ≥ 38.0°C or 100.4°F) * Chills * Fatigue * Headache * Muscle aches/myalgias * Joint aches/arthralgias * Nausea * Vomiting * Abdominal pain * Diarrhea

Time frame:
From vaccination to 7 days post vaccination (Days 1-7)
Reported as:
Count of participants · Participants
Number of Participants With Solicited Adverse Events (AEs) 7 Days After First Dose of Study Vaccine
ParticipantsGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
Any Solicited Event11122515109137
Fever00000000
Chills15111010
Fatigue581797795
Headache571073563
Muscle Aches/Myalgias26632212
Joint Aches/Arthralgias14221211
Nausea22621180
Vomiting02011000
Abdominal pain55436152
Diarrhea24963633
PrimaryNumber of Participants With Solicited Adverse Events 7 Days After Second Dose of Study Vaccine

Solicited AEs are pre-specified 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 included: * Fever (oral temperature ≥ 38.0°C or 100.4°F) * Chills * Fatigue * Headache * Muscle aches/myalgias * Joint aches/arthralgias * Nausea * Vomiting * Abdominal pain * Diarrhea

Time frame:
From Day 29 to Day 35
Reported as:
Count of participants · Participants
Number of Participants With Solicited Adverse Events 7 Days After Second Dose of Study Vaccine
ParticipantsGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
Any Solicited Event——1612——67
Fever——10——01
Chills——12——01
Fatigue——86——13
Headache——95——32
Muscle Aches/Myalgias——43——11
Joint Aches/Arthralgias——14——10
Nausea——32——31
Vomiting——01——10
Abdominal pain——42——10
Diarrhea——44——33
PrimaryNumber of Participants With Unsolicited Adverse Events (AEs) up 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 were reported as an AE.

Time frame:
From vaccination to 28 days post vaccination (Day 1-28 for 1st vaccination and Day 29-56 for the 2nd vaccination)
Reported as:
Count of participants · Participants
Number of Participants With Unsolicited Adverse Events (AEs) up to 28 Days Post Vaccination
ParticipantsGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
After 1st dose7721104132
After 2nd dose——167——23
SecondaryMedian Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV

Blood samples collected from participants for type-specific poliovirus neutralizing antibodies were analyzed at the Polio and Picornavirus Laboratory Branch at the United States Centers for Disease Control and Prevention (CDC). For all immunogenicity endpoints, data are presented separately by: * Prior vaccination history (exclusively IPV vs OPV), and * Type-specific poliovirus vaccine received (type 1 vs type 3).

Time frame:
Baseline and Day 29 (28 days post-vaccination)
Reported as:
Median · log₂ titer
Median Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV
log₂ titerGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)
Baseline5.67 (5.34 to 7.33)6.00 (5.83 to 7.50)
Day 29NA (NA to NA)NA (NA to NA)
SecondaryMedian Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
Time frame:
Baseline, Day 29 (28 days post-vaccination) and Day 57 (28 days after 2nd vaccination)
Reported as:
Median · log₂ titer
Median Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
log₂ titerGroup 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)
Baseline6.83 (6.17 to 7.83)7.17 (5.50 to 8.17)
Day 29NA (NA to NA)NA (10.17 to NA)
Day 57NA (NA to NA)NA (NA to NA)
SecondaryMedian Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV
Time frame:
Baseline and Day 29 (28 days post-vaccination)
Reported as:
Median · log₂ titer
Median Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV
log₂ titerGroup 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)
Baseline6.17 (5.83 to 8.17)6.17 (5.50 to 6.83)
Day 29NA (NA to NA)NA (9.50 to NA)
SecondaryMedian Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
Time frame:
Baseline, Day 29 (28 days after the 1st vaccination) and Day 57 (28 days after 2nd vaccination)
Reported as:
Median · log₂ titer
Median Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
log₂ titerGroup 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
Baseline5.83 (4.17 to 6.83)6.50 (5.17 to 8.50)
Day 29NA (NA to NA)NA (9.50 to NA)
Day 57NA (NA to NA)9.83 (9.17 to NA)
SecondaryGeometric Mean Titer (GMT) of Anti-poliovirus Type 1 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV

GMT and 95% confidence intervals are maximum likelihood estimates incorporating left and right censoring at the lower limit of quantitation (LLOQ) and ULOQ, respectively.

Time frame:
Baseline and Day 29 (28 days post-vaccination)
Reported as:
Geometric mean · titer
Geometric Mean Titer (GMT) of Anti-poliovirus Type 1 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV
titerGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)
Baseline49.6 (26.7 to 92.1)73.2 (33.6 to 159.7)
Day 295208.2 (904.6 to 29986.4)2846.7 (716.6 to 11307.6)
Statistical analysis
  • Group1: nOPV1 (IPV History) vs Group 2: mOPV1 (IPV History) · Gmt ratio: 0.68 · 95% CI 0.252 to 1.838GMT ratios (nOPV/mOPV) were estimated via a linear model of the log₂ neutralizing antibody titer as a function of group with a fixed parameter for site and a covariate for the baseline log₂ neutralizing antibody titer level.
SecondaryGeometric Mean Titer of Anti-poliovirus Type 1 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
Time frame:
Baseline, Day 29 (28 days after 1st vaccination) and Day 57 (28 days after 2nd vaccination)
Reported as:
Geometric mean · titer
Geometric Mean Titer of Anti-poliovirus Type 1 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
titerGroup 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)
Baseline111.6 (70.5 to 176.5)116.0 (48.1 to 280.1)
Day 2910869.2 (1953.5 to 60474.3)4495.1 (960.9 to 21027.0)
Day 574407.5 (1547.8 to 12551.0)16500.8 (808.4 to 336813.5)
Statistical analysis
  • Group 3: nOPV1 (OPV History) vs Group 4: mOPV1 (OPV History) · Gmt ratio: 1.26 · 95% CI 0.232 to 6.833GMT ratios (nOPV/mOPV) were estimated via a linear model of the log₂ neutralizing antibody titer as a function of group with a fixed parameter for site and a covariate for the baseline log₂ neutralizing antibody titer level.
  • Group 3: nOPV1 (OPV History) vs Group 4: mOPV1 (OPV History) · Gmt ratio: 1.98 · 95% CI 0.603 to 6.528GMT ratios (nOPV/mOPV) were estimated via a linear model of the log₂ neutralizing antibody titer as a function of group with a fixed parameter for site and a covariate for the baseline log₂ neutralizing antibody titer level.
SecondaryGeometric Mean Titer of Anti-poliovirus Type 3 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV
Time frame:
Baseline and Day 29 (28 days post-vaccination)
Reported as:
Geometric mean · titer
Geometric Mean Titer of Anti-poliovirus Type 3 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV
titerGroup 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)
Baseline113.0 (56.7 to 225.2)74.6 (43.2 to 128.8)
Day 293091.2 (1095.6 to 8721.9)3945.5 (736.6 to 21132.6)
Statistical analysis
  • Group 5: nOPV3 (IPV History) vs Group 6: mOPV3 (IPV History) · Gmt ratio: 1.56 · 95% CI 0.639 to 3.828GMT ratios (nOPV/mOPV) were estimated via a linear model of the log₂ neutralizing antibody titer as a function of group with a fixed parameter for site and a covariate for the baseline log₂ neutralizing antibody titer level.
SecondaryGeometric Mean Titer of Anti-poliovirus Type 3 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
Time frame:
Baseline, Day 29 (28 days after 1st vaccination) and Day 57 (28 days after 2nd vaccination)
Reported as:
Geometric mean · titer
Geometric Mean Titer of Anti-poliovirus Type 3 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
titerGroup 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
Baseline53.4 (29.1 to 97.8)101.1 (47.7 to 214.5)
Day 292810.1 (1364.0 to 5789.3)1483.8 (758.8 to 2901.4)
Day 573337.0 (1293.1 to 8611.7)1076.8 (613.5 to 1890.0)
Statistical analysis
  • Group 7: nOPV3 (OPV History) vs Group 8: mOPV3 (OPV History) · Gmt ratio: 1.79 · 95% CI 0.772 to 4.163GMT ratios (nOPV/mOPV) were estimated via a linear model of the log₂ neutralizing antibody titer as a function of group with a fixed parameter for site and a covariate for the baseline log₂ neutralizing antibody titer level.
  • Group 7: nOPV3 (OPV History) vs Group 8: mOPV3 (OPV History) · Gmt ratio: 2.51 · 95% CI 0.994 to 6.340GMT ratios (nOPV/mOPV) were estimated via a linear model of the log₂ neutralizing antibody titer as a function of group with a fixed parameter for site and a covariate for the baseline log₂ neutralizing antibody titer level.
SecondaryPercentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Vaccination Among Participants With a Vaccine History of IPV

* Seroconversion (SCR) is defined as a minimum 4-fold increase in titer from Baseline (pre-vaccination) to 28 days post-vaccination among those participants with a 4-fold increase possible to observe, i.e., with a Baseline titer not greater than 8.5 log₂. * Minimum 2-fold-rise from Baseline to 28 days post-vaccination among those participants with a 2-fold increase possible to observe, i.e., with a Baseline titer not greater than 9.5 log₂. * Any fold-rise is defined as any increase in titer from Baseline to 28 days post-vaccination (log₂ neutralizing antibody titer post-dose minus Baseline \> 0), among those with an increase possible to observe, i.e., with a Baseline titer less than 10.5 log₂.

Time frame:
Baseline (pre-vaccination) and Day 29 (28 days post-vaccination)
Reported as:
Number · percentage of participants
Percentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Vaccination Among Participants With a Vaccine History of IPV
percentage of participantsGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)
≥ 4-fold rise88.9 (65.29 to 98.62)92.9 (66.13 to 99.82)
≥ 2-fold rise94.4 (72.71 to 99.86)100 (76.84 to 100)
Any fold-rise100 (81.47 to 100)100 (76.84 to 100)
Statistical analysis
  • Group1: nOPV1 (IPV History) vs Group 2: mOPV1 (IPV History) · Fisher Exact · p = >0.999 · Rate difference: -4.0 · 95% CI -27.67 to 22.72Rate Difference = nOPV - mOPV
SecondaryPercentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Each Vaccination Among Participants With a Vaccine History of OPV

* Seroconversion (SCR) is defined as a minimum 4-fold increase in titer from Baseline (pre-vaccination) to 28 days post-vaccination among those participants with a 4-fold increase possible to observe, i.e., with a Baseline titer not greater than 8.5 log₂. * Minimum 2-fold-rise from Baseline to 28 days post-vaccination among those participants with a 2-fold increase possible to observe, i.e., with a Baseline titer not greater than 9.5 log₂. * Any fold-rise is defined as any increase in titer from Baseline to 28 days post-vaccination (log₂ neutralizing antibody titer post-dose minus Baseline \> 0), among those with an increase possible to observe, i.e., with a Baseline titer less than 10.5 log₂.

Time frame:
Baseline, Day 29 (28 days post-vaccination) and Day 57 (28 days after 2nd vaccination)
Reported as:
Number · percentage of participants
Percentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Each Vaccination Among Participants With a Vaccine History of OPV
percentage of participantsGroup 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)
Day 29: ≥ 4-fold rise86.1 (70.50 to 95.33)88.9 (65.29 to 98.62)
Day 29: ≥ 2-fold rise83.3 (68.64 to 93.03)90.0 (68.30 to 98.77)
Day 29: Any fold-rise83.0 (69.19 to 92.35)100 (83.16 to 100)
Day 57: ≥ 4-fold rise97.1 (85.08 to 99.93)88.9 (65.29 to 98.62)
Day 57: ≥ 2-fold rise95.1 (83.47 to 99.40)94.7 (73.97 to 99.87)
Day 57: Any fold-rise97.8 (88.47 to 99.94)94.7 (73.97 to 99.87)
Statistical analysis
  • Group 3: nOPV1 (OPV History) vs Group 4: mOPV1 (OPV History) · Fisher Exact · p = >0.999 · Rate difference: -2.8 · 95% CI -20.47 to 20.86Rate Difference = nOPV - mOPV
  • Group 3: nOPV1 (OPV History) vs Group 4: mOPV1 (OPV History) · Fisher Exact · p = 0.263 · Rate difference: 8.3 · 95% CI -5.71 to 30.57Rate Difference = nOPV - mOPV
SecondaryPercentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Vaccination Among Participants With a Vaccine History of IPV

* Seroconversion (SCR) is defined as a minimum 4-fold increase in titer from Baseline (pre-vaccination) to 28 days post-vaccination among those participants with a 4-fold increase possible to observe, i.e., with a Baseline titer not greater than 8.5 log₂. * Minimum 2-fold-rise from Baseline to 28 days post-vaccination among those participants with a 2-fold increase possible to observe, i.e., with a Baseline titer not greater than 9.5 log₂. * Any fold-rise is defined as any increase in titer from Baseline to 28 days post-vaccination (log₂ neutralizing antibody titer post-dose minus Baseline \> 0), among those with an increase possible to observe, i.e., with a Baseline titer less than 10.5 log₂.

Time frame:
Baseline and Day 29 (28 days post-vaccination)
Reported as:
Number · percentage of participants
Percentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Vaccination Among Participants With a Vaccine History of IPV
percentage of participantsGroup 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)
≥ 4-fold rise100 (78.20 to 100)85.7 (57.9 to 98.22)
≥ 2-fold rise94.1 (71.31 to 99.85)100 (78.20 to 100)
Any fold-rise94.4 (72.71 to 99.86)100 (78.20 to 100)
Statistical analysis
  • Group 5: nOPV3 (IPV History) vs Group 6: mOPV3 (IPV History) · Fisher Exact · p = 0.224 · Rate difference: 14.3 · 95% CI -8.30 to 40.45Rate Difference = nOPV - mOPV
SecondaryPercentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Each Vaccination Among Participants With a Vaccine History of OPV

* Seroconversion (SCR) is defined as a minimum 4-fold increase in titer from Baseline (pre-vaccination) to 28 days post-vaccination among those participants with a 4-fold increase possible to observe, i.e., with a Baseline titer not greater than 8.5 log₂. * Minimum 2-fold-rise from Baseline to 28 days post-vaccination among those participants with a 2-fold increase possible to observe, i.e., with a Baseline titer not greater than 9.5 log₂. * Any fold-rise is defined as any increase in titer from Baseline to 28 days post-vaccination (log₂ neutralizing antibody titer post-dose minus Baseline \> 0), among those with an increase possible to observe, i.e., with a Baseline titer less than 10.5 log₂.

Time frame:
Baseline, Day 29 (28 days after 1st vaccination) and Day 57 (28 days after 2nd vaccination)
Reported as:
Number · percentage of participants
Percentage of Participants With Any-Fold Rise, 2-fold Rise and 4-fold Rise in Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers From Baseline to 28 Days After Each Vaccination Among Participants With a Vaccine History of OPV
percentage of participantsGroup 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
Day 29: ≥ 4-fold rise96.4 (81.65 to 99.91)86.7 (59.54 to 98.34)
Day 29: ≥ 2-fold rise96.9 (83.78 to 99.92)83.3 (58.58 to 96.42)
Day 29: Any fold-rise94.1 (80.32 to 99.28)94.4 (72.71 to 99.86)
Day 57: ≥ 4-fold rise96.4 (81.65 to 99.91)78.6 (49.20 to 95.34)
Day 57: ≥ 2-fold rise90.6 (74.98 to 98.02)76.5 (50.10 to 93.19)
Day 57: Any fold-rise100 (89.72 to 100)88.2 (63.56 to 98.54)
Statistical analysis
  • Group 7: nOPV3 (OPV History) vs Group 8: mOPV3 (OPV History) · Fisher Exact · p = 0.275 · Rate difference: 9.8 · 95% CI -7.29 to 35.19Rate Difference = nOPV - mOPV
  • Group 7: nOPV3 (OPV History) vs Group 8: mOPV3 (OPV History) · Fisher Exact · p = 0.100 · Rate difference: 17.9 · 95% CI -1.27 to 44.93Rate Difference = nOPV - mOPV
SecondaryTime to Cessation of Fecal Shedding of Vaccine Virus in Participants With IPV Vaccination History

The presence of the vaccine virus in stool samples was 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). The time to cessation of fecal shedding of nOPV1 and nOPV3 in prior IPV recipients was estimated using Kaplan-Meier methodology with interval-censoring.

Time frame:
Up to Day 57
Reported as:
Median · days
Time to Cessation of Fecal Shedding of Vaccine Virus in Participants With IPV Vaccination History
daysGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)
Time to Cessation of Fecal Shedding of Vaccine Virus in Participants With IPV Vaccination History22 (15 to 24)20 (20 to 29)20 (15 to 37)29 (22 to 42)
SecondaryTime to Cessation of Fecal Shedding of Vaccine Virus in Participants With OPV Vaccination History

The presence of the vaccine virus in stool samples was 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). The time to cessation of fecal shedding of nOPV1 and nOPV3 in prior OPV recipients was evaluated separately after each dose, estimated using Kaplan-Meier methodology with interval-censoring.

Time frame:
From vaccination through 28 days after each vaccination
Reported as:
Median · days
Time to Cessation of Fecal Shedding of Vaccine Virus in Participants With OPV Vaccination History
daysGroup 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
After first dose20 (9 to 20)20 (14 to 20)21 (13 to NA)17 (8 to NA)
After 2nd dose5 (NA to NA)7 (4 to 7)2 (NA to NA)2 (NA to NA)
SecondaryPercentage of Participants Shedding Type 1 Vaccine Virus at Each Post-vaccination Stool Collection in Participants With IPV Vaccination History

Presence of the vaccine virus in stool samples was assessed by polymerase chain reaction (PCR). This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

Time frame:
Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57
Reported as:
Number · percentage of participants
Percentage of Participants Shedding Type 1 Vaccine Virus at Each Post-vaccination Stool Collection in Participants With IPV Vaccination History
percentage of participantsGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)
Day 362.5 (35.4 to 84.8)82.4 (56.6 to 96.2)
Day 593.3 (68.1 to 99.8)100 (75.3 to 100)
Day 8100 (80.5 to 100)100 (81.5 to 100)
Day 10100 (80.5 to 100)100 (79.4 to 100)
Day 1594.1 (71.3 to 99.9)81.3 (54.4 to 96.0)
Day 2250.0 (26.0 to 74.0)43.8 (19.8 to 70.1)
Day 2922.2 (6.4 to 47.6)26.7 (7.8 to 55.1)
Day 3630.8 (9.1 to 61.4)13.3 (1.7 to 40.5)
Day 430.0 (0.0 to 21.8)6.7 (0.2 to 31.9)
Day 500.0 (0.0 to 18.5)0.0 (0.0 to 23.2)
Day 570.0 (0.0 to 20.6)0.0 (0.0 to 23.2)
At any time point100 (81.5 to 100)100 (81.5 to 100)
SecondaryPercentage of Participants Shedding Type 3 Vaccine Virus at Each Post-vaccination Stool Collection in Participants With IPV Vaccination History

Presence of the vaccine virus in stool samples was assessed by polymerase chain reaction (PCR). This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

Time frame:
Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57
Reported as:
Number · percentage of participants
Percentage of Participants Shedding Type 3 Vaccine Virus at Each Post-vaccination Stool Collection in Participants With IPV Vaccination History
percentage of participantsGroup 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)
Day 388.2 (63.6 to 98.5)71.4 (41.9 to 91.6)
Day 5100 (80.5 to 100)100 (73.5 to 100)
Day 8100 (80.5 to 100)100 (76.8 to 100)
Day 1093.8 (69.8 to 99.8)100 (75.3 to 100)
Day 1576.5 (50.1 to 93.2)93.3 (68.1 to 99.8)
Day 2238.9 (17.3 to 64.3)61.5 (31.6 to 86.1)
Day 2938.9 (17.3 to 64.3)50.0 (23.0 to 77.0)
Day 3627.8 (9.7 to 53.5)33.3 (9.9 to 65.1)
Day 4311.8 (1.5 to 36.4)7.1 (0.2 to 33.9)
Day 500.0 (0.0 to 19.5)7.1 (0.2 to 33.9)
Day 570.0 (0.0 to 19.5)6.7 (0.2 to 31.9)
At any time point100 (82.4 to 100)100 (78.2 to 100)
SecondaryAmount of Type 1 Vaccine Virus in Each Stool Sample Positive for Virus in Participants With IPV Vaccination History

Samples positive for vaccine virus in stool as detected by PCR were quantified using a cell culture infectious dose assay. Participants who were PCR-positive for type 1 viral shedding but with log₁₀ CCID50 per gram ≤ LLOQ contributed a value equal to the LLOQ. This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

Time frame:
Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57
Reported as:
Median · log₁₀ CCID50 per gram
Amount of Type 1 Vaccine Virus in Each Stool Sample Positive for Virus in Participants With IPV Vaccination History
log₁₀ CCID50 per gramGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)
Day 32.94 (2.750 to 3.875)3.22 (2.750 to 4.211)
Day 53.22 (2.922 to 4.125)4.28 (3.906 to 4.875)
Day 83.41 (2.813 to 4.000)4.33 (4.109 to 4.609)
Day 103.19 (2.938 to 3.719)4.08 (3.063 to 4.531)
Day 152.75 (2.750 to 2.813)2.75 (2.750 to 2.781)
Day 222.75 (2.750 to 3.219)2.75 (2.750 to 3.313)
Day 292.77 (2.750 to 2.781)2.88 (2.750 to 3.625)
Day 362.75 (2.750 to 3.313)2.91 (2.750 to 3.063)
Day 43—3.34 (3.34 to 3.34)
SecondaryAmount of Type 3 Vaccine Virus in Each Stool Sample Positive for Virus in Participants With IPV Vaccination History

Samples positive for vaccine virus in stool as detected by PCR were quantified using a cell culture infectious dose assay. Participants who were PCR-positive for type 3 viral shedding but with log₁₀ CCID50 per gram ≤ LLOQ contributed a value equal to the LLOQ. This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

Time frame:
Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57
Reported as:
Median · log₁₀ CCID50 per gram
Amount of Type 3 Vaccine Virus in Each Stool Sample Positive for Virus in Participants With IPV Vaccination History
log₁₀ CCID50 per gramGroup 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)
Day 34.06 (2.938 to 4.750)4.00 (2.781 to 4.734)
Day 53.88 (2.906 to 4.500)4.23 (3.063 to 4.672)
Day 84.28 (3.094 to 4.594)4.42 (3.094 to 4.875)
Day 104.16 (2.844 to 4.375)3.97 (3.000 to 4.938)
Day 152.84 (2.750 to 3.063)3.02 (2.766 to 3.469)
Day 222.75 (2.750 to 2.781)3.09 (2.875 to 4.125)
Day 292.75 (2.750 to 2.813)2.78 (2.750 to 2.844)
Day 362.78 (2.750 to 3.281)2.75 (2.750 to 3.844)
Day 432.77 (2.750 to 2.781)2.97 (2.97 to 2.97)
Day 50—2.81 (2.81 to 2.81)
Day 57—3.78 (3.78 to 3.78)
SecondaryShedding Index of Vaccine Virus Shedding in Stool in Participants With IPV Vaccination History

The Shedding Index Endpoint (SIE) was 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). Participants who were PCR-positive for type-specific viral shedding but with log₁₀ CCID50 per gram ≤ LLOQ contributed a value equal to the LLOQ. This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

Time frame:
Days 8, 15, 22, and 29
Reported as:
Median · log₁₀ CCID50 per gram
Shedding Index of Vaccine Virus Shedding in Stool in Participants With IPV Vaccination History
log₁₀ CCID50 per gramGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)
Shedding Index of Vaccine Virus Shedding in Stool in Participants With IPV Vaccination History1.88 (1.477 to 2.344)1.96 (1.734 to 2.477)2.20 (1.844 to 3.016)2.41 (1.766 to 3.578)
SecondaryArea Under the Curve From Vaccination to 28 Days After Vaccination (AUC₀-₂₈) of Vaccine Virus Shed in Stool in Participants With an IPV Vaccination History

Area under the curve (AUC) was computed for each participant using CCID50 per gram data collected through Day 29 using the linear trapezoidal rule. Participants were assumed to be not shedding at time of vaccination (i.e. there was no stool collection on Day 1). Participants who were PCR-positive for type-specific viral shedding but with log₁₀ CCID50 per gram ≤ LLOQ contributed a value equal to the LLOQ. This endpoint was pre-specified to be analyzed in participants with IPV vaccination history.

Time frame:
Days 3, 5, 8, 10, 15, 22, and 29
Reported as:
Median · days * log₁₀ CCID50/gram
Area Under the Curve From Vaccination to 28 Days After Vaccination (AUC₀-₂₈) of Vaccine Virus Shed in Stool in Participants With an IPV Vaccination History
days * log₁₀ CCID50/gramGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)
Area Under the Curve From Vaccination to 28 Days After Vaccination (AUC₀-₂₈) of Vaccine Virus Shed in Stool in Participants With an IPV Vaccination History57.84 (10.188 to 66.625)66.88 (52.797 to 78.344)60.80 (49.172 to 80.438)71.46 (56.711 to 87.945)

Adverse events

Collected over All-cause mortality and serious AEs were collected up to Day 169. Non-serious AEs were collected up to 28 days after each vaccination (Day 1-28 for 1st vaccination and Day 29-56 for the 2nd vaccination). Solicited AEs were collected up to 7 days after each vaccination (Days 1-7 for 1st vaccination and Days 29-35 for the 2nd vaccination).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Group1: nOPV1 (IPV History)0/21 (0%)0/20 (0%)13/20 (65%)
Group 2: mOPV1 (IPV History)0/23 (0%)0/20 (0%)13/20 (65%)
Group 3: nOPV1 (OPV History)0/53 (0%)0/50 (0%)39/50 (78%)
Group 4: mOPV1 (OPV History)0/27 (0%)0/25 (0%)21/25 (84%)
Group 5: nOPV3 (IPV History)0/20 (0%)0/19 (0%)12/19 (63.2%)
Group 6: mOPV3 (IPV History)0/21 (0%)0/17 (0%)10/17 (58.8%)
Group 7: nOPV3 (OPV History)0/40 (0%)0/35 (0%)15/35 (42.9%)
Group 8: mOPV3 (OPV History)0/21 (0%)0/19 (0%)12/19 (63.2%)
Most frequent other events
Showing 10 of 73
Most frequent other events
EventGroup1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)
FatigueGeneral disorders5/208/2021/5011/257/198/179/357/19
DiarrhoeaGastrointestinal disorders3/204/2011/5010/253/197/175/355/19
HeadacheNervous system disorders5/207/2016/5010/253/196/178/355/19
Abdominal painGastrointestinal disorders5/205/207/504/256/191/175/352/19
MyalgiaMusculoskeletal and connective tissue disorders2/206/2010/506/252/192/172/352/19
ChillsGeneral disorders1/205/203/503/251/190/171/351/19
ArthralgiaMusculoskeletal and connective tissue disorders1/204/204/506/251/192/172/351/19
NauseaGastrointestinal disorders2/202/208/503/251/191/178/351/19
VomitingGastrointestinal disorders0/202/200/502/251/190/171/350/19
COVID-19Infections and infestations2/200/202/502/250/190/171/350/19

Baseline characteristics

The Safety Population was defined as all participants who provided informed consent and who received a study vaccine, and for whom no potential transmission events between participants were identified by next generation sequencing of shed virus (Cohorts 1 and 3 only).

Age, Continuous
Age, Continuous(years)Group1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)Total
Mean20.8 ± 2.620.0 ± 1.630.0 ± 6.330.0 ± 6.520.7 ± 2.121.5 ± 2.430.4 ± 6.633.1 ± 8.827.1 ± 5.7
Sex: Female, Male
Sex: Female, Male(Participants)Group1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)Total
Female10925151072113110
Male8925109814689
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Group1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)Total
Hispanic or Latino0060202010
Not Hispanic or Latino1818442417133319186
Unknown or Not Reported000102003
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Group1: nOPV1 (IPV History)Group 2: mOPV1 (IPV History)Group 3: nOPV1 (OPV History)Group 4: mOPV1 (OPV History)Group 5: nOPV3 (IPV History)Group 6: mOPV3 (IPV History)Group 7: nOPV3 (OPV History)Group 8: mOPV3 (OPV History)Total
American Indian or Alaska Native000001001
Asian2151113115
Native Hawaiian or Other Pacific Islander000000000
Black or African American01315217938
White16164022139128136
More than one race002000215
Unknown or Not Reported000102104
07

Study locations

4 sites
  • Pharmaron CPC, Inc.
    Baltimore, Maryland 21201, United States
  • Dartmouth Hitchcock Medical Center
    Lebanon, New Hampshire 03756, United States
  • University of North Carolina Institute for Global Health and Infectious Diseases (IGHID)
    Chapel Hill, North Carolina 27599-7215, United States
  • University of Vermont Vaccine Testing Center
    Burlington, Vermont 05405, United States
08

References and documents

Study documents

  • Study protocol · Feb 17, 2022
  • Statistical analysis plan · Apr 13, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT04529538
Lead sponsor
PATH
Collaborators
Bill and Melinda Gates Foundation, Centers for Disease Control and Prevention, Viroclinics Biosciences B.V., The Emmes Company, LLC
Responsible party
Sponsor
First posted
Aug 27, 2020
Start date
Mar 26, 2021
Primary completion
Feb 17, 2023
Completion
Feb 17, 2023
Results posted
Sep 25, 2024
Last update
Nov 20, 2024

Study contacts

Jessica Crothers, MD
principal investigator · University of Vermont
Arlene Sena, MD
principal investigator · University of North Carolina
Peter Wright, MD
principal investigator · Dartmouth-Hitchcock Medical Center
Mohamed Al-Ibrahim, MB CHB, FACP
principal investigator · Pharmaron CPC, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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