Clinical trial NCT04529538: Study of Novel Types 1 and 3 Oral Poliomyelitis Vaccines
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Poliomyelitis
Keywords: Vaccine tolerability
Vaccine reactogenicity
Vaccine viral shedding
Vaccine immunogenicity
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: Centers for Disease Control and Prevention
name: Viroclinics Biosciences B.V.
name: The Emmes Company, LLC
First posted: 2020-08-27
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: It will be an 8-arm, randomized, observer-blind, controlled trial
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: 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:

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)

Primary outcomes:
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Day 1 to end of study, up to 169 days
measure: Number of Participants With Solicited Adverse Events (AEs) 7 Days After First Dose of Study Vaccine
timeFrame: From vaccination to 7 days post vaccination (Days 1-7)
measure: Number of Participants With Solicited Adverse Events 7 Days After Second Dose of Study Vaccine
timeFrame: From Day 29 to Day 35
measure: Number of Participants With Unsolicited Adverse Events (AEs) up to 28 Days Post Vaccination
timeFrame: From vaccination to 28 days post vaccination (Day 1-28 for 1st vaccination and Day 29-56 for the 2nd vaccination)
Secondary outcomes:
measure: Median Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV
timeFrame: Baseline and Day 29 (28 days post-vaccination)
measure: Median Anti-poliovirus Type 1 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
timeFrame: Baseline, Day 29 (28 days post-vaccination) and Day 57 (28 days after 2nd vaccination)
measure: Median Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV
timeFrame: Baseline and Day 29 (28 days post-vaccination)
measure: Median Anti-poliovirus Type 3 Serum Neutralizing Antibody Titers at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
timeFrame: Baseline, Day 29 (28 days after the 1st vaccination) and Day 57 (28 days after 2nd vaccination)
measure: 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
timeFrame: Baseline and Day 29 (28 days post-vaccination)
measure: Geometric Mean Titer of Anti-poliovirus Type 1 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
timeFrame: Baseline, Day 29 (28 days after 1st vaccination) and Day 57 (28 days after 2nd vaccination)
measure: Geometric Mean Titer of Anti-poliovirus Type 3 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of IPV
timeFrame: Baseline and Day 29 (28 days post-vaccination)
measure: Geometric Mean Titer of Anti-poliovirus Type 3 Serum Neutralizing Antibodies at Baseline and Post-vaccination Among Participants With a Vaccine History of OPV
timeFrame: Baseline, Day 29 (28 days after 1st vaccination) and Day 57 (28 days after 2nd vaccination)
measure: 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
timeFrame: Baseline (pre-vaccination) and Day 29 (28 days post-vaccination)
measure: 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
timeFrame: Baseline, Day 29 (28 days post-vaccination) and Day 57 (28 days after 2nd vaccination)
measure: 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
timeFrame: Baseline and Day 29 (28 days post-vaccination)
measure: 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
timeFrame: Baseline, Day 29 (28 days after 1st vaccination) and Day 57 (28 days after 2nd vaccination)
measure: Time to Cessation of Fecal Shedding of Vaccine Virus in Participants With IPV Vaccination History
timeFrame: Up to Day 57
measure: Time to Cessation of Fecal Shedding of Vaccine Virus in Participants With OPV Vaccination History
timeFrame: From vaccination through 28 days after each vaccination
measure: Percentage of Participants Shedding Type 1 Vaccine Virus at Each Post-vaccination Stool Collection in Participants With IPV Vaccination History
timeFrame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57
measure: Percentage of Participants Shedding Type 3 Vaccine Virus at Each Post-vaccination Stool Collection in Participants With IPV Vaccination History
timeFrame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57
measure: Amount of Type 1 Vaccine Virus in Each Stool Sample Positive for Virus in Participants With IPV Vaccination History
timeFrame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57
measure: Amount of Type 3 Vaccine Virus in Each Stool Sample Positive for Virus in Participants With IPV Vaccination History
timeFrame: Days 3, 5, 8, 10, 15, 22, 29, 36, 43, 50, and 57
measure: Shedding Index of Vaccine Virus Shedding in Stool in Participants With IPV Vaccination History
timeFrame: Days 8, 15, 22, and 29
measure: 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
timeFrame: Days 3, 5, 8, 10, 15, 22, and 29
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Pharmaron CPC, Inc.
state: Maryland
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Chapel Hill
country: United States
facility: University of North Carolina Institute for Global Health and Infectious Diseases (IGHID)
state: North Carolina
city: Burlington
country: United States
facility: University of Vermont Vaccine Testing Center
state: Vermont
Study officials:
affiliation: University of Vermont
name: Jessica Crothers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina
name: Arlene Sena, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center
name: Peter Wright, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pharmaron CPC, Inc.
name: Mohamed Al-Ibrahim, MB CHB, FACP
role: PRINCIPAL_INVESTIGATOR
References: