NCT04232943

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

A Phase 1 Randomized Study to Examine the Safety, Tolerability, and Immunogenicity of Inactivated Poliovirus Vaccine (IPV) With or Without E.Coli Double Mutant Heat Labile Toxin (dmLT) and Impact on Poliovirus Shedding Post-bOPV Challenge in Healthy IPV-Primed Adult Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 87 (actual)
• Sponsor: PATH · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
BIOLOGICAL	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
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.
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.

Timeline

• Start date: 2020-01-22
• Primary completion: 2021-02-01
• Completion: 2021-02-01
• First posted: 2020-01-18
• Last updated: 2022-09-06
• Results posted: 2022-09-06

Locations

1 site across 1 country: Belgium