Study of a Novel Type 3 Oral Poliomyelitis Vaccine in Panama

NCT ID: NCT05654467

Last Updated: 2024-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

1532 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-05

Study Completion Date

2025-11-20

Brief Summary

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The purpose of this clinical trial is to assess the safety and tolerability (primary objective), immunogenicity (primary and secondary objectives), fecal shedding of vaccine viruses (secondary objective) and the potential for neurovirulence of shed virus (secondary objective) of a novel oral polio type 3 vaccine, nOPV3, as compared to Sabin monovalent type 3 vaccine controls (mOPV3), in healthy young children (192 subjects), infants (860 subjects), and neonates (480 subjects).

Detailed Description

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This multicentered, 12-arm phase 2 study will be the first pediatric evaluation of nOPV3 in healthy young children, infants, and newborns. This trial will be initiated once results in the adult phase 1 study of nOPV3 indicate that there are no safety concerns, and that the vaccine elicits demonstrable immunogenicity. Additionally, prior to enrolling into cohort 2, the adult phase 1 data must show no concerning signals of reversion of attenuating sites from a subset of Next Generation Sequencing.

This study is intended to provide critical data on safety, immunogenicity, and genetic stability, as well as to demonstrate the vaccine's ability to reduce fecal shedding following a challenge with the Sabin type 3 strain.

Enrollment in this pediatric study will be staggered into three age-descending cohorts of 6 treatment groups of escalated target dose levels for the nOPV3 vaccine: cohort 1 composed of 192 healthy young children 1 to \<5 years of age who have completed their full routine polio immunization series; cohort 2 composed of 860 healthy infants 6 weeks of age not previously vaccinated (OPV/IPV) who will be primed with a dose of inactivated poliomyelitis vaccine (IPV) prior to OPV3 vaccination \[a subset, of the infants (n=360) will also receive the challenge virus\]; and cohort 3, composed of 480 healthy poliomyelitis unvaccinated neonates (day of birth +3 days).

Progression into the next cohort and groups within cohorts will depend on safety evaluations of the prior Phase 1 adult trial and Day 8 safety evaluation of the previous groups in prior cohorts in the study.

Conditions

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Poliomyelitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

A 12-arm, randomized, observer-blind, controlled, age de-escalation, dosage escalation study.
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group 1: Young Children, nOPV3 10^5.5 CCID50

48 young children aged 1 to \<5 years will receive 2 doses of nOPV3 at a dose level of 10\^5.5 CCID50 on Day 1 and Day 29

Group Type EXPERIMENTAL

Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

Intervention Type BIOLOGICAL

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Group 3: Young Children, nOPV3 10^6.0 CCID50

48 young children aged 1 to \<5 years will receive 2 doses of nOPV3 at a dose level of 10\^6.0 CCID50 on Day 1 and Day 29

Group Type EXPERIMENTAL

Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

Intervention Type BIOLOGICAL

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Group 5: Young Children, nOPV3 10^6.5 CCID50

48 young children aged 1 to \<5 years will receive 2 doses of nOPV3 at a dose level of 10\^6.5 CCID50 on Day 1 and Day 29

Group Type EXPERIMENTAL

Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

Intervention Type BIOLOGICAL

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Groups 2, 4 and 6: Young Children, mOPV3

48 young children aged 1 to \<5 years will receive 2 doses of mOPV3 at a dose level of ≥ 10\^5.8 CCID50 on Day 1 and Day 29

Group Type ACTIVE_COMPARATOR

Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)

Intervention Type BIOLOGICAL

The Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 control and challenge vaccine (mOPV3) containing ≥ 10\^5.8 CCID50 per dose.

Group 7: Infants, nOPV3 10^5.5 CCID50

240 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV3 at a dose level of 10\^5.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.

Group Type EXPERIMENTAL

Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

Intervention Type BIOLOGICAL

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)

Intervention Type BIOLOGICAL

The Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 control and challenge vaccine (mOPV3) containing ≥ 10\^5.8 CCID50 per dose.

Group 9: Infants, nOPV3 10^5.5 CCID50

240 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV3 at a dose level of 10\^6.0 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.

Group Type EXPERIMENTAL

Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

Intervention Type BIOLOGICAL

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)

Intervention Type BIOLOGICAL

The Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 control and challenge vaccine (mOPV3) containing ≥ 10\^5.8 CCID50 per dose.

Group 11: Infants, nOPV3 10^6.5 CCID50

140 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV3 at a dose level of 10\^6.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.

Group Type EXPERIMENTAL

Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

Intervention Type BIOLOGICAL

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)

Intervention Type BIOLOGICAL

The Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 control and challenge vaccine (mOPV3) containing ≥ 10\^5.8 CCID50 per dose.

Groups 8, 10 and 12: Infants, mOPV3

240 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of mOPV3 at a dose level of ≥ 10\^5.8 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.

Group Type ACTIVE_COMPARATOR

Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)

Intervention Type BIOLOGICAL

The Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 control and challenge vaccine (mOPV3) containing ≥ 10\^5.8 CCID50 per dose.

Group 13: Neonates, nOPV3 10^5.5 CCID50

120 neonates (day of birth + 3 days) will receive 2 doses of nOPV3 at a dose level of 10\^5.5 CCID50 on Day 1 and Day 29.

Group Type EXPERIMENTAL

Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

Intervention Type BIOLOGICAL

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Group 15: Neonates, nOPV3 10^6.0 CCID50

120 neonates (day of birth + 3 days) will receive 2 doses of nOPV3 at a dose level of 10\^6.0 CCID50 on Day 1 and Day 29.

Group Type EXPERIMENTAL

Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

Intervention Type BIOLOGICAL

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Group 17: Neonates, nOPV3 10^6.5 CCID50

120 neonates (day of birth + 3 days) will receive 2 doses of nOPV3 at a dose level of 10\^6.5 CCID50 on Day 1 and Day 29.

Group Type EXPERIMENTAL

Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

Intervention Type BIOLOGICAL

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Groups 14, 16 and 18: Neonates, mOPV

120 neonates (day of birth + 3 days) will receive 2 doses of mOPV3 at a dose level of ≥ 10\^5.8 CCID50 on Day 1 and Day 29

Group Type ACTIVE_COMPARATOR

Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)

Intervention Type BIOLOGICAL

The Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 control and challenge vaccine (mOPV3) containing ≥ 10\^5.8 CCID50 per dose.

Interventions

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Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

The nOPV3 vaccine containing approximately 10\^5.5, 10\^6.0, or 10\^6.5 CCID50 per dose.

Intervention Type BIOLOGICAL

Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)

The Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 control and challenge vaccine (mOPV3) containing ≥ 10\^5.8 CCID50 per dose.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Healthy, as defined by the absence of any clinically significant medical condition or congenital anomaly as determined by medical history, physical examination, and clinical assessment of the investigator.
2. Parent(s) or guardian(s) willing and able to provide written informed consent prior to performance of any study-specific procedure.
3. Resides in study area and parent(s) or guardian(s) understands and is able and willing to adhere to all study visits and procedures (as evidenced by a signed informed consent form \[ICF\] and assessment by the investigator).
4. Parent(s) or guardian(s) agrees for participant to receive all routine infant and childhood immunizations as per the approved protocol adjusted schedule.


1. Male or female child from ≥1 to \<5 years-of-age at the time of initial study vaccination.
2. Based on available documentation or parental/guardian(s) report, previously completed the primary poliomyelitis immunization series for the jurisdiction, with last dose received more than 28 days prior to initial study vaccination.


1. Male or female infant expected to be 6 weeks of age (43rd to 49th day of life \[with day of birth being the first day of life\], inclusive + 6 day window), at the time of initial study vaccination.
2. Prior to study vaccination has received no doses of IPV or OPV, based on no evidence of such vaccination per available parental/guardian(s) report or documentation.


1. Male or female newborn (1st day of life + 3-day window), at the time of initial study vaccination.
2. Prior to study vaccination has received no doses of IPV or OPV vaccine, based on no evidence of such vaccination per available parental/guardian(s) report or documentation.

Exclusion Criteria

1. For all participants the presence of anyone under 10 years of age in the participant's household (living in the same house or apartment unit) who does not have complete "age appropriate" vaccination status with respect to poliovirus vaccines at the time of study vaccine administration. For household members younger than 10 years of age appropriate vaccination is complete series of the primary poliomyelitis immunization series for the jurisdiction.
2. For all participants having a member of the participant's household (living in the same house or apartment unit) who has received OPV based on the vaccination records in the previous three months before study vaccine administration.
3. Any participating children attending day care or pre-school during their participation in the study until one month after their last study vaccine administration.
4. Moderate or severe (grade ≥ 2) acute illness at the time of enrollment/first study vaccination-temporary exclusion (see Appendix II: Severity Grading Tables). Participant with mild (grade 1) acute illnesses may be enrolled at the discretion of the investigator.
5. Presence of fever on the day of enrollment/first study vaccination (axillary temperature

≥37.5˚C)-(Temporary exclusion for cohorts 1 and 2). If resolved in 48 hrs., can be enrolled.
6. A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin).
7. Any self-reported known or suspected immunosuppressive or immunodeficiency condition (including HIV infection) in the participant or household member (living under the same roof/in the same building rather than in the same compound).
8. Receipt of any systemic immune-modifying or immunosuppressant drugs prior to the first study vaccine dose or planned use during the study of study participants or a household member.
9. Any known or suspected bleeding disorder in the participant that would pose a risk to venipuncture or intramuscular injection.
10. Presence of severe malnutrition (weight-for-length/height z-score ≤-3SD median \[per WHO published child growth standards\])-temporary exclusion if marginal and subsequently gains weight.
11. 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.
12. Receipt of transfusion of any blood product or immunoglobulins within 12 months prior to the first administration of study vaccine or planned use during the study period.
13. Parent(s) or guardian(s) or participant has any condition 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).


1. Premature birth (less than 37 weeks gestation or less than 2500 grams birth weight).
2. From multiple birth (due to increased risk of OPV transmissions between siblings).
Minimum Eligible Age

1 Day

Maximum Eligible Age

4 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

PT Bio Farma

INDUSTRY

Sponsor Role collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role collaborator

Technical Resources International, Inc. (TRI)

UNKNOWN

Sponsor Role collaborator

PATH

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Xavier Saez-Llorens, MD

Role: PRINCIPAL_INVESTIGATOR

Cevaxin

Locations

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Cevaxin - 24 de Diciembre

Panama City, , Panama

Site Status RECRUITING

Cevaxin - Chorrera

Panama City, , Panama

Site Status RECRUITING

Cevaxin-- Avenida Mexico

Panama City, , Panama

Site Status RECRUITING

Countries

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Panama

Central Contacts

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Xavier Saez-Llorens, MD

Role: CONTACT

+507 203-9760

Facility Contacts

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Xavier Saez-Llorens, MD

Role: primary

+507 203-9760

Xavier Saez-Llorens

Role: primary

+507 2039760

Xavier Saez-Llorens, MD

Role: primary

+507 203-9760

Other Identifiers

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U1111-1285-1905

Identifier Type: OTHER

Identifier Source: secondary_id

CVIA 101

Identifier Type: -

Identifier Source: org_study_id

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