Inactivated Poliovirus Vaccine (IPV) With or Without E.Coli Double Mutant Heat-Labile Toxin (dmLT) Challenge Study in Healthy Adults

NCT ID: NCT04232943

Last Updated: 2022-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-22
• Study Completion Date: 2021-02-01

Brief Summary

In this study, the safety and tolerability of inactivated polio vaccine (IPV) co-administered with dmLT will be assessed, as well as whether co-administration of dmLT with IPV enhances mucosal responses compared to those with IPV alone.

Detailed Description

A major component of the strategy aimed at worldwide eradication of polio advanced by the World Health Organization (WHO) is based on the replacement of oral polio vaccine (OPV) with IPV; however, IPV is not efficient in preventing person-to-person poliovirus transmission, particularly in settings of poor hygiene, due to limited impact on intestinal mucosal immunity compared to OPV. The addition of an adjuvant, in particular one that may direct the response towards mucosal homing may offset that deficiency.

In this study, the safety and tolerability of IPV co-administered with dmLT will be assessed, as well as whether co-administration of dmLT with IPV enhances mucosal responses to polioviruses types 1, 2, and 3 in comparison with administration of IPV alone and provides greater mucosal immunity, assessed following oral bOPV challenge. The positive control arm (bOPV) is included in order to confirm the level of shedding observable following a dose of an oral vaccine known to develop intestinal immunity.

Conditions

Polio

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Inactivated Poliomyelitis Vaccine (IPV)

Participants will receive a single intramuscular injection of 0.5 mL inactivated poliomyelitis vaccine (IPV) on Day 1 followed by a single dose (2 drops) of bivalent oral polio vaccine (bOPV) 28 days later.

Group Type: ACTIVE_COMPARATOR

Inactivated Poliomyelitis Vaccine (IPV)

Intervention Type: BIOLOGICAL

IMOVAX® Polio is a highly purified, inactivated poliovirus vaccine. Each 0.5 mL dose contains:

• Type 1 (Mahoney) 40 D-antigen units
• Type 2 (MEF1) 8 D-antigen units
• Type 3 (Saukett) 32 D-antigen units

Bivalent Oral Polio Vaccine (bOPV)

Intervention Type: BIOLOGICAL

Polio Sabin™ One and Three (oral) is a bivalent, live attenuated poliomyelitis virus vaccine of the Sabin strains Type 1 (LSc, 2ab) and Type 3 (Leon 12a, 1b), propagated in MRC5 human diploid cells.

Each dose (0.1 mL) contains not less than 10⁶ 50% cell culture infectious dose (CCID₅₀) of Type 1 and 10⁵·⁸ CCID₅₀ of Type 3.

Inactivated Poliomyelitis Vaccine + dmLT

Participants will receive a single intramuscular injection of 0.5 mL IPV co-administered with 0.5 μg of dmLT on Day 1 followed by a single dose (2 drops) of bOPV 28 days later.

Group Type: EXPERIMENTAL

Inactivated Poliomyelitis Vaccine (IPV)

Intervention Type: BIOLOGICAL

IMOVAX® Polio is a highly purified, inactivated poliovirus vaccine. Each 0.5 mL dose contains:

• Type 1 (Mahoney) 40 D-antigen units
• Type 2 (MEF1) 8 D-antigen units
• Type 3 (Saukett) 32 D-antigen units

E.coli Double Mutant Heat-Labile Toxin (dmLT) (adjuvant)

Intervention Type: BIOLOGICAL

LT (R192G/L211A), or "dmLT," is a protein toxoid derived from wild-type enterotoxigenic Escherichia coli (ETEC) labile toxin (LT). The LT toxin has been shown to have inherent mucosal adjuvant properties for co-administered antigens and thus has potential as a mucosal adjuvant for different co-administered vaccines. LT has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites, which are critical for activation of the secreted toxin molecules.

Bivalent Oral Polio Vaccine (bOPV)

Intervention Type: BIOLOGICAL

Polio Sabin™ One and Three (oral) is a bivalent, live attenuated poliomyelitis virus vaccine of the Sabin strains Type 1 (LSc, 2ab) and Type 3 (Leon 12a, 1b), propagated in MRC5 human diploid cells.

Each dose (0.1 mL) contains not less than 10⁶ 50% cell culture infectious dose (CCID₅₀) of Type 1 and 10⁵·⁸ CCID₅₀ of Type 3.

Bivalent Oral Polio Vaccine

Participants will receive one dose (2 drops) of bOPV on Day 1 followed by a second dose of bOPV 28 days later.

Group Type: ACTIVE_COMPARATOR

Bivalent Oral Polio Vaccine (bOPV)

Intervention Type: BIOLOGICAL

Polio Sabin™ One and Three (oral) is a bivalent, live attenuated poliomyelitis virus vaccine of the Sabin strains Type 1 (LSc, 2ab) and Type 3 (Leon 12a, 1b), propagated in MRC5 human diploid cells.

Each dose (0.1 mL) contains not less than 10⁶ 50% cell culture infectious dose (CCID₅₀) of Type 1 and 10⁵·⁸ CCID₅₀ of Type 3.

Interventions

Inactivated Poliomyelitis Vaccine (IPV)

IMOVAX® Polio is a highly purified, inactivated poliovirus vaccine. Each 0.5 mL dose contains:

• Type 1 (Mahoney) 40 D-antigen units
• Type 2 (MEF1) 8 D-antigen units
• Type 3 (Saukett) 32 D-antigen units

Intervention Type: BIOLOGICAL

E.coli Double Mutant Heat-Labile Toxin (dmLT) (adjuvant)

LT (R192G/L211A), or "dmLT," is a protein toxoid derived from wild-type enterotoxigenic Escherichia coli (ETEC) labile toxin (LT). The LT toxin has been shown to have inherent mucosal adjuvant properties for co-administered antigens and thus has potential as a mucosal adjuvant for different co-administered vaccines. LT has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites, which are critical for activation of the secreted toxin molecules.

Intervention Type: BIOLOGICAL

Bivalent Oral Polio Vaccine (bOPV)

Polio Sabin™ One and Three (oral) is a bivalent, live attenuated poliomyelitis virus vaccine of the Sabin strains Type 1 (LSc, 2ab) and Type 3 (Leon 12a, 1b), propagated in MRC5 human diploid cells.

Each dose (0.1 mL) contains not less than 10⁶ 50% cell culture infectious dose (CCID₅₀) of Type 1 and 10⁵·⁸ CCID₅₀ of Type 3.

Intervention Type: BIOLOGICAL

Other Intervention Names

IMOVAX® Polio Vaccine; LT (R192G/L211A); Polio Sabin™ One and Three (Oral)

Eligibility Criteria

Inclusion Criteria

• Adult male or female, ages 18-45, inclusive
• Healthy as defined by absence of clinically significant medical condition, either acute or chronic, as determined by medical history and clinical assessment
• History of prior receipt of at least 3 doses of IPV
• Willing and able to provide written informed consent and willing to comply with study requirements
• Intention to remain in the area during the study period
• If female and of childbearing potential, not breastfeeding and not pregnant (based on a negative serum pregnancy test at screening and negative urine pregnancy tests prior to vaccine administration and bOPV challenge), planning to avoid pregnancy until at least three months after bOPV challenge, and willing to use an adequate method of contraception consistently. Effective methods include intrauterine device or hormonal contraceptives (oral, injectable, patch, implant, vaginal ring). Women with credible history of abstinence or in monogamous relationship with a vasectomized partner are also eligible.

Exclusion Criteria

• History of receiving any OPV at any time
• Receipt of IPV in the last five years
• History of or planned household contact with an individual receiving OPV in prior 4 weeks, or at any point during the study
• Regular contact with children younger than six months (and thus not yet fully vaccinated against polio) and immunocompromised individuals
• Presence of fever on the day of vaccination (oral temperature ≥ 38°C)
• Received an investigational product within 30 days prior to randomization or planning to participate in another research study involving investigational product during the conduct of this study
• Presence of any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune diseases) as determined by medical history and/or physical examination that would compromise the participant's health or is likely to result in nonconformance to the protocol or would interfere with the evaluation of responses according to the opinion of the investigator
• History of allergic disease or known hypersensitivity to any component of the study vaccine
• History of anaphylactic reaction
• Receipt of any immunoglobulin therapy and/or blood products in the last 6 months or planned administration during the study period
• History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including oral steroids, parenteral steroids, or high-dose inhaled steroids (> 800 μg/day of beclomethasone dipropionate or equivalent), in the last 6 months to either the study subject or their close household contacts (those on nasal or topical steroids may be permitted to participate in the study)
• Symptoms of an acute self-limited illness, such as an upper respiratory infection or gastroenteritis, including a temperature ≥ 38.0°C, within the 7 days prior to study vaccines administration
• Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody
• Clinically significant screening laboratory value
• History of receipt of experimental E. coli, enterotoxigenic E. coli (ETEC) labile toxin (LT), or cholera vaccines or live E. coli or Vibrio cholerae challenges.
• Receipt of any licensed vaccine within 28 days before enrollment in this study or plans to receive any licensed vaccine between enrollment and 28 days after the bOPV challenge
• History of alcohol or drug abuse in the last 5 years
• Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled, or could interfere with the evaluation of the study vaccine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

PATH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Antwerpen

Antwerp, Wilrijk, Belgium

Countries

Belgium

References

Erdem R, De Coster I, Withanage K, Mercer LD, Marchant A, Taton M, Cools N, Lion E, Cassels F, Higgins D, Ivinson K, Locke E, Mahmood K, Wright PF, Gast C, White JA, Ackerman ME, Konopka-Anstadt JL, Mainou BA, Van Damme P. Safety, tolerability, and immunogenicity of inactivated poliovirus vaccine with or without E.coli double mutant heat-labile toxin (dmLT) adjuvant in healthy adults; a phase 1 randomized study. Vaccine. 2023 Mar 3;41(10):1657-1667. doi: 10.1016/j.vaccine.2023.01.048. Epub 2023 Feb 4.

Reference Type: DERIVED

PMID: 36746739 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002415-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CVIA 065

Identifier Type: -

Identifier Source: org_study_id