Study of Novel Types 1 and 3 Oral Poliomyelitis Vaccines

NCT04529538 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CVIA 076
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 4

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.

Conditions

Poliomyelitis

Keywords

Vaccine tolerability; Vaccine reactogenicity; Vaccine viral shedding; Vaccine immunogenicity

Outcome Measures

Primary Outcomes (4)

• 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

  From Day 1 to end of study, up to 169 days

• 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

  From vaccination to 7 days post vaccination (Days 1-7)

• 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

  From Day 29 to Day 35

• 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.

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

Secondary Outcomes (20)

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

  Baseline and Day 29 (28 days post-vaccination)

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

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

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

  Baseline and Day 29 (28 days post-vaccination)

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

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

• 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

  Baseline and Day 29 (28 days post-vaccination)

Study Arms (8)

Group1: nOPV1 (IPV History)

EXPERIMENTAL

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)

Group 2: mOPV1 (IPV History)

ACTIVE COMPARATOR

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)

Group 3: nOPV1 (OPV History)

EXPERIMENTAL

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)

Group 4: mOPV1 (OPV History)

ACTIVE COMPARATOR

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)

Group 5: nOPV3 (IPV History)

EXPERIMENTAL

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)

Group 6: mOPV3 (IPV History)

ACTIVE COMPARATOR

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)

Group 7: nOPV3 (OPV History)

EXPERIMENTAL

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)

Group 8: mOPV3 (OPV History)

ACTIVE COMPARATOR

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

Novel Oral Polio Vaccine Type 1 (nOPV1) BIOLOGICAL

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

Group 3: nOPV1 (OPV History); Group1: nOPV1 (IPV History)

Novel Oral Polio Vaccine Type 3 (nOPV3) BIOLOGICAL

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

Group 5: nOPV3 (IPV History); Group 7: nOPV3 (OPV History)

Sabin Monovalent Oral Polio Vaccine Type 1 (mOPV1) BIOLOGICAL

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

Group 2: mOPV1 (IPV History); Group 4: mOPV1 (OPV History)

Sabin Monovalent Oral Polio Vaccine Type 3 (mOPV3) BIOLOGICAL

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

Group 6: mOPV3 (IPV History); Group 8: mOPV3 (OPV History)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females, from 18 to 45 years of age (inclusive) at the time of enrollment
• 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
• Willing and able to provide written informed consent prior to performance of any study-specific procedure
• 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

You may not qualify if:

• 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)
• Receipt of polio vaccine within 12 months before the start of the study
• Having Crohn's disease or ulcerative colitis or having had major surgery of the gastrointestinal tract involving significant loss or resection of the bowel
• A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin)
• 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 \[LLN\])
• 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)
• 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)
• Will have household direct or close professional contact during the study with pregnant women
• 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)
• Will have professional handling of food, catering, or food production activities during the study
• Reside in homes with septic tanks
• 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)
• 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
• 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
• 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.

Sponsors & Collaborators

• PATH: lead
• Bill and Melinda Gates Foundation: collaborator
• Centers for Disease Control and Prevention: collaborator
• Viroclinics Biosciences B.V.: collaborator
• The Emmes Company, LLC: collaborator

Study Sites (4)

Pharmaron CPC, Inc.

Baltimore, Maryland, 21201, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

University of North Carolina Institute for Global Health and Infectious Diseases (IGHID)

Chapel Hill, North Carolina, 27599-7215, United States

Location

University of Vermont Vaccine Testing Center

Burlington, Vermont, 05405, United States

Location

Related Publications (2)

• Mercer LD, Sena AC, Colgate ER, Crothers JW, Wright PF, Al-Ibrahim M, Tritama E, Vincent A, Mainou BA, Zhang Y, Konopka-Anstadt J, Bandyopadhyay AS, Fix A, Konz JO, Gast C. Safety and immunogenicity of novel live attenuated type 1 and type 3 oral poliomyelitis vaccines in healthy adults in the USA: a first-in-human, observer-masked, multicentre, phase 1 randomised controlled trial. Lancet Infect Dis. 2025 Dec;25(12):1363-1376. doi: 10.1016/S1473-3099(25)00285-3. Epub 2025 Aug 13.

  PMID: 40818478 DERIVED

• Thompson KM, Kalkowska DA, Kidd SE, Burns CC, Badizadegan K. Trade-offs of different poliovirus vaccine options for outbreak response in the United States and other countries that only use inactivated poliovirus vaccine (IPV) in routine immunization. Vaccine. 2024 Feb 6;42(4):819-827. doi: 10.1016/j.vaccine.2023.12.081. Epub 2024 Jan 12.

  PMID: 38218668 DERIVED

MeSH Terms

Conditions

Poliomyelitis

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Chris Gast, Ph.D.
• Organization: PATH

cgast@path.org

206-285-3500

Study Officials

• Jessica Crothers, MD

  University of Vermont

  PRINCIPAL INVESTIGATOR

• Arlene Sena, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

• Peter Wright, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

• Mohamed Al-Ibrahim, MB CHB, FACP

  Pharmaron CPC, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: It will be an 8-arm, randomized, observer-blind, controlled trial

Study Record Dates

• First Submitted: August 24, 2020
• First Posted: August 27, 2020
• Study Start: March 26, 2021
• Primary Completion: February 17, 2023
• Study Completion: February 17, 2023
• Last Updated: November 20, 2024
• Results First Posted: September 25, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)