Clinical trial NCT04232943: Inactivated Poliovirus Vaccine (IPV) With or Without E.Coli Double Mutant Heat-Labile Toxin (dmLT) Challenge Study in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Polio
Keywords: inactivated polio vaccine (IPV)
double mutant [LT(R192G/L211A)] Enterotoxigenic E coli heat toxin (dmLT)
Lead sponsor: PATH
Sponsor class: OTHER
First posted: 2020-01-18
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants With Serious Adverse Events Over the Course of the Study
timeFrame: Up to 6 months
measure: Number of Participants With Severe Adverse Events During the 28 Days Following Study Vaccination
timeFrame: Up to 28 days after study vaccination (prior to bOPV challenge)
measure: Number of Participants With Solicited Local Adverse Events
timeFrame: 7 days following study vaccination
measure: Number of Participants With Solicited Systemic Adverse Events
timeFrame: 7 days following study vaccination
measure: Number of Participants With Unsolicited Adverse Events During the 28 Days Following Study Vaccination
timeFrame: 28 days following study vaccination
measure: Percentage of Participants Positive for bOPV Viral Shedding 7 Days Following bOPV Challenge
timeFrame: Day 36 (7 days after bOPV challenge)
Secondary outcomes:
measure: Percentage of Participants With a Positive Poliovirus Fecal Neutralization Response 28 Days After Vaccination and 14 Days After bOPV Challenge
timeFrame: Day 29 (28 days after study vaccination) and Day 43 (14 days after bOPV challenge)
measure: Level of Fecal Poliovirus Immunoglobulin A (IgA) Antibodies at Baseline, 28 Days After Vaccination and 14 Days After bOPV Challenge
timeFrame: Baseline (before vaccination), Day 29 (28 days after study vaccination, prior to bOPV challenge) and Day 43 (14 days after bOPV challenge)
measure: Change From Baseline in Fecal Poliovirus IgA Antibodies 28 Days After Study Vaccination and 14 Days After bOPV Challenge
timeFrame: Baseline, Day 29 (28 days after study vaccination, prior to bOPV challenge) and Day 43 (14 days after bOPV challenge)
measure: Serum Neutralizing Antibody Seroconversion Rate 28 Days After Study Vaccination
timeFrame: Day 29 (28 days after study vaccination, prior to bOPV challenge)
measure: Geometric Mean Titer of Serum Poliovirus Neutralizing Antibodies at Baseline and 28 Days After Study Vaccination
timeFrame: Baseline (pre-vaccination) and Day 29 (28 days after study vaccination, prior to bOPV challenge)
measure: Seroprotection Rate of Serum Poliovirus Neutralizing Antibodies at Baseline and 28 Days Following Vaccination
timeFrame: Baseline (before vaccination) and Day 29 (28 days after vaccination, prior to bOPV challenge)
measure: Geometric Mean Fold-Rise in Serum Poliovirus Neutralizing Antibodies
timeFrame: Baseline (before vaccination) and Day 29 (28 days after vaccination, prior to bOPV challenge)
measure: Percentage of Participants With a Circulating Poliovirus IgA Antibody-Secreting Cell Response
timeFrame: Baseline (pre-vaccination), Day 8 (7 days after study vaccination), Day 29 (28 days after study vaccination prior to bOPV challenge), and Day 36 (7 days after bOPV challenge)
measure: Number of Circulating Poliovirus IgA Antibody Secreting Cells at Baseline and After Study Vaccination
timeFrame: Baseline (pre-vaccination), Day 8 (7 days after study vaccination), Day 29 (28 days after study vaccination prior to bOPV challenge), and Day 36 (7 days after bOPV challenge)
measure: Percentage of Participants With a Circulating Poliovirus Immunoglobulin G (IgG) Antibody-Secreting Cell Response
timeFrame: Baseline (pre-vaccination), Day 8 (7 days after study vaccination), Day 29 (28 days after study vaccination prior to bOPV challenge), and Day 36 (7 days after bOPV challenge)
measure: Number of Circulating Poliovirus IgG Antibody Secreting Cells at Baseline and After Study Vaccination
timeFrame: Baseline (pre-vaccination), Day 8 (7 days after study vaccination), Day 29 (28 days after study vaccination prior to bOPV challenge), and Day 36 (7 days after bOPV challenge)
measure: Area Under the Curve (AUC) of Viral Shedding in Stool for 28 Days After bOPV Challenge
timeFrame: Days 33, 36, 43, 50, and 57 (i.e., 4, 7, 14, 21, and 28 days, respectively, following bOPV challenge).
measure: Time to Cessation of Viral Shedding in Stool After bOPV Challenge
timeFrame: Days 33, 36, 39, 43, 46, 50, and 57
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: University of Antwerpen
state: Wilrijk
Study officials:
References: