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

NCT04232943 | Completed Phase 1 Results DMC

• 2 other identifiers: CVIA 0652019-002415-25
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

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.

Conditions

Polio

Keywords

inactivated polio vaccine (IPV); double mutant [LT(R192G/L211A)] Enterotoxigenic E coli heat toxin (dmLT)

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Serious Adverse Events Over the Course of the Study

  A serious adverse event (SAE) was any event that resulted in any of the following outcomes: 1. Death; 2. Was life-threatening; 3. Required inpatient hospitalization or prolongation of existing hospitalization; 4. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; 5. Congenital abnormality or birth defect; 6. Important medical event that did not result in one of the above outcomes but jeopardized the health of the study participant or required medical or surgical intervention to prevent one of the outcomes listed in the above definition of SAE.

  Up to 6 months

• Number of Participants With Severe Adverse Events During the 28 Days Following Study Vaccination

  Severe adverse events are events that interrupted a participant's usual daily activity and may have required systemic drug therapy or other treatment. Severe events are usually potentially life-threatening or incapacitating.

  Up to 28 days after study vaccination (prior to bOPV challenge)

• Number of Participants With Solicited Local Adverse Events

  Solicited adverse events (AEs) are pre-specified local and systemic adverse events that are common or known to be associated with vaccination and that are actively monitored as indicators of vaccine reactogenicity. Local/injection site reactions included pain, erythema/redness, swelling, induration, and hyperpigmentation, applicable to participants in the IPV and IPV + dmLT arms who received study injections. Severity was graded according to the following: Mild: Transient or mild discomfort; does not interfere with activities, erythema or swelling 2.5 - 5 cm, hyperpigmentation 1- 4 cm. Moderate: Mild to moderate limitation in activity; no or minimal medical intervention/therapy required, erythema or swelling 5.1 - 10 cm, hyperpigmentation 4.1 - 8 cm, or repeated use of nonnarcotic pain reliever \> 24 hours. Severe: All normal activity is prevented for 24 hours or more, erythema or swelling \> 10 cm, hyperpigmentation \> 8 cm, or any use of narcotic pain reliever.

  7 days following study vaccination

• Number of Participants With Solicited Systemic Adverse Events

  Systemic reactions included fever (oral temperature ≥ 38.0°C), chills, fatigue, headache, muscle aches/myalgia, joint ache/arthralgia, rash, nausea, vomiting, and diarrhea. Severity was graded according to the following: Mild: Transient or mild discomfort; does not interfere with activities, 2-3 vomiting episodes in 24 hours, 3-5 loose stools/day or diarrhea volume \<1000 mL/day, or temperature 38.0 - 38.9˚C. Moderate: Mild to moderate limitation in activity; no or minimal medical intervention/therapy required, 4-5 vomiting episodes in 24 hours, 6-9 loose stools/day or 1000-1999 mL output per 24 hours, or temperature 39.0 - 39.9˚C. Severe: All normal activity is prevented for 24 hours or more, \> 6 vomiting episodes in 24 hours, \> 10 loose stools/day or orthostatic hypotension, or temperature \> 40.0˚C.

  7 days following study vaccination

• Number of Participants With Unsolicited Adverse Events During the 28 Days Following Study Vaccination

  An adverse event is any untoward medical occurrence in a participant after administration of the investigational vaccine and that does not necessarily have a causal relationship with the investigational vaccine. AEs were graded for severity on the following scale: Grade 1 - Mild: Transient or mild discomfort; does not interfere with activities; Grade 2 - Moderate: Mild to moderate limitation in activity; no or minimal medical intervention/therapy required; Grade 3 - Severe: All normal activity is prevented for 24 hours or more.

  28 days following study vaccination

• Percentage of Participants Positive for bOPV Viral Shedding 7 Days Following bOPV Challenge

  The presence of the bOPV virus (Sabin strains Type 1 and Type 3) in stool samples was determined using polymerase chain reaction (PCR).

  Day 36 (7 days after bOPV challenge)

Secondary Outcomes (13)

• Percentage of Participants With a Positive Poliovirus Fecal Neutralization Response 28 Days After Vaccination and 14 Days After bOPV Challenge

  Day 29 (28 days after study vaccination) and Day 43 (14 days after bOPV challenge)

• Level of Fecal Poliovirus Immunoglobulin A (IgA) Antibodies at Baseline, 28 Days After Vaccination and 14 Days After bOPV Challenge

  Baseline (before vaccination), Day 29 (28 days after study vaccination, prior to bOPV challenge) and Day 43 (14 days after bOPV challenge)

• Change From Baseline in Fecal Poliovirus IgA Antibodies 28 Days After Study Vaccination and 14 Days After bOPV Challenge

  Baseline, Day 29 (28 days after study vaccination, prior to bOPV challenge) and Day 43 (14 days after bOPV challenge)

• Serum Neutralizing Antibody Seroconversion Rate 28 Days After Study Vaccination

  Day 29 (28 days after study vaccination, prior to bOPV challenge)

• Geometric Mean Titer of Serum Poliovirus Neutralizing Antibodies at Baseline and 28 Days After Study Vaccination

  Baseline (pre-vaccination) and Day 29 (28 days after study vaccination, prior to bOPV challenge)

Study Arms (3)

Inactivated Poliomyelitis Vaccine (IPV)

ACTIVE COMPARATOR

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.

Biological: Inactivated Poliomyelitis Vaccine (IPV); Biological: Bivalent Oral Polio Vaccine (bOPV)

Inactivated Poliomyelitis Vaccine + dmLT

EXPERIMENTAL

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.

Biological: Inactivated Poliomyelitis Vaccine (IPV); Biological: E.coli Double Mutant Heat-Labile Toxin (dmLT) (adjuvant); Biological: Bivalent Oral Polio Vaccine (bOPV)

Bivalent Oral Polio Vaccine

ACTIVE COMPARATOR

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

Biological: Bivalent Oral Polio Vaccine (bOPV)

Interventions

Inactivated Poliomyelitis Vaccine (IPV) 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

Also known as: IMOVAX® Polio Vaccine

Inactivated Poliomyelitis Vaccine (IPV); Inactivated Poliomyelitis Vaccine + dmLT

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

Also known as: LT (R192G/L211A)

Inactivated Poliomyelitis Vaccine + dmLT

Bivalent Oral Polio Vaccine (bOPV) 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.

Also known as: Polio Sabin™ One and Three (Oral)

Bivalent Oral Polio Vaccine; Inactivated Poliomyelitis Vaccine (IPV); Inactivated Poliomyelitis Vaccine + dmLT

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

University of Antwerpen

Antwerp, Wilrijk, Belgium

Location

Related Publications (1)

• 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.

  PMID: 36746739 DERIVED

MeSH Terms

Conditions

Poliomyelitis

Interventions

Poliovirus Vaccine, Inactivated; Adjuvants, Pharmaceutic

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

Intervention Hierarchy (Ancestors)

Vaccines, Inactivated; Vaccines; Biological Products; Complex Mixtures; Poliovirus Vaccines; Viral Vaccines; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Results Point of Contact

• Title: Rahsan Erdem, MD, Senior Medical Officer
• Organization: PATH

rerdem@path.org

+1 202 540 4546

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study vaccine for Groups 1 and 2 (IPV alone and IPV + dmLT) will be administered IM in a blinded fashion. An unblinded positive control group (Group 3) will be administered bOPV. The unblinded Research Pharmacist will perform all preparations of the study product for Groups 1 and 2. Preparation of the study product and administration to the subjects will occur in separate locations to preserve the blinding of staff except for Research Pharmacist. The study subjects, the study personnel who perform study assessments after administration of study product, data entry personnel at the site, and laboratory personnel performing immunologic assays will be blinded to the treatment assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will receive a single dose of licensed trivalent IPV, administered intramuscularly (IM), with or without dmLT, or bOPV, administered orally (PO). IPV or IPV + dmLT will be administered to groups of 30 participants each. Both participants and clinical staff will be blinded to group assignment (IPV alone vs IPV + dmLT). A positive unblinded control group will be included, composed of 20 participants receiving bOPV. One month (28 days) after receiving study vaccine, all participants will receive a standard oral dose of bOPV to assess relative impact of study vaccine on shedding of that challenge virus.

Study Record Dates

• First Submitted: January 13, 2020
• First Posted: January 18, 2020
• Study Start: January 22, 2020
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: September 6, 2022
• Results First Posted: September 6, 2022

Record last verified: 2022-01

Locations

BE (1)