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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Polio
- Sponsor
- PATH
- Enrollment
- 87
- Locations
- 1
- Primary Endpoint
- Number of Participants With Unsolicited Adverse Events During the 28 Days Following Study Vaccination
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
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
Outcomes
Primary Outcomes
Number of Participants With Unsolicited Adverse Events During the 28 Days Following Study Vaccination
Time Frame: 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.
Number of Participants With Solicited Local Adverse Events
Time Frame: 7 days following study vaccination
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.
Number of Participants With Solicited Systemic Adverse Events
Time Frame: 7 days following study vaccination
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.
Number of Participants With Serious Adverse Events Over the Course of the Study
Time Frame: Up to 6 months
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.
Number of Participants With Severe Adverse Events During the 28 Days Following Study Vaccination
Time Frame: Up to 28 days after study vaccination (prior to bOPV challenge)
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.
Percentage of Participants Positive for bOPV Viral Shedding 7 Days Following bOPV Challenge
Time Frame: Day 36 (7 days after 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).
Secondary Outcomes
- Seroprotection Rate of Serum Poliovirus Neutralizing Antibodies at Baseline and 28 Days Following Vaccination(Baseline (before vaccination) and Day 29 (28 days after vaccination, prior to 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))
- Percentage of Participants With a Circulating Poliovirus IgA Antibody-Secreting Cell Response(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))
- 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))
- Geometric Mean Fold-Rise in Serum Poliovirus Neutralizing Antibodies(Baseline (before vaccination) and Day 29 (28 days after 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))
- Percentage of Participants With a Circulating Poliovirus Immunoglobulin G (IgG) Antibody-Secreting Cell Response(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))
- Area Under the Curve (AUC) of Viral Shedding in Stool for 28 Days After bOPV Challenge(Days 33, 36, 43, 50, and 57 (i.e., 4, 7, 14, 21, and 28 days, respectively, following bOPV challenge).)
- Time to Cessation of Viral Shedding in Stool After bOPV Challenge(Days 33, 36, 39, 43, 46, 50, and 57)
- Number of Circulating Poliovirus IgA Antibody Secreting Cells at Baseline and After Study Vaccination(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))
- Number of Circulating Poliovirus IgG Antibody Secreting Cells at Baseline and After Study Vaccination(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))