A Study on the Immune Response and Safety of a Combined Vaccine Against Diphtheria, Tetanus and Acellular Pertussis (dTpa) in Japanese Healthy Pregnant Women

Official title

A Phase 3, Non-Randomized, Single-Arm, Open-Label Study to Assess the Immunogenicity, Safety and Reactogenicity of a Single Dose of Combined Reduced-Antigen-Content Diphtheria, Tetanus and Acellular Pertussis (dTpa) Vaccine in Japanese Healthy Pregnant Women

Overview

The purpose of this Phase 3, non-randomized, single-arm, open-label study is to evaluate the immune response, reactogenicity and safety of GSKs dTpa vaccine in Japanese pregnant women between 27 weeks and less than 37 weeks of pregnancy. Both the pregnant women and their neonates born during the study will be evaluated for specific analyses.

Interventions

• Biological dTpa
  1 dose of dTpa vaccine is administered intramuscularly.

Primary outcome measures

• Number of seropositive healthy pregnant women for anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies [Time frame: At Month 1 post-vaccination]
• Number of seropositive participants for anti-PT, anti-FHA and anti-PRN antibodies from samples in cord blood sample at birth [Time frame: On the Day of birth]

Secondary outcome measures (12)

• Booster response to pertussis (PT, FHA and PRN) antigens in healthy pregnant women [Time frame: At Month 1]
• Antibody concentration for antibodies against pertussis (PT, FHA, PRN) in healthy pregnant women [Time frame: On Day 1 (day of vaccination) and at Month 1 post-vaccination]
• Antibody concentration for anti-diphtheria and anti-tetanus antibodies in healthy pregnant women [Time frame: On Day 1 (day of vaccination) and at Month 1 post-vaccination]
• Number of seroprotected healthy pregnant women for anti-diphtheria and anti-tetanus antibodies [Time frame: On Day 1 (day of vaccination) and at Month 1 post-vaccination]
• Antibody concentration for antibodies against pertussis (PT, FHA, PRN) in the cord blood of the neonates born to mothers that received dTpa vaccine during pregnancy [Time frame: On the Day of birth]
• Antibody concentration for anti-diphtheria and anti-tetanus antibodies in cord blood of the neonates born to mothers that received dTpa vaccine during pregnancy [Time frame: On the Day of birth]
• Number of seroprotected neonates for anti-diphtheria and anti-tetanus antibodies, from samples in cord blood [Time frame: On the Day of birth]
• Number of healthy pregnant women with solicited administration site adverse events [Time frame: From Day 1 (day of vaccination) to Day 7 post-vaccination]
• Number of healthy pregnant women with solicited systemic adverse events (AEs) [Time frame: From Day 1 (day of vaccination) to Day 7 post-vaccination]
• Number of healthy pregnant women with unsolicited adverse events [Time frame: From Day 1 (day of vaccination) to Day 30 post-vaccination]
• Number of healthy pregnant women with serious adverse events (SAEs) [Time frame: From Day 1 (day of vaccination) and up to 1-month post-delivery (study end)]
• Number of healthy pregnant women with AEs and SAEs leading to study withdrawal [Time frame: From the Day 1 (day of vaccination) and up to 1-month post-delivery (study end)]

Eligibility criteria

Inclusion criteria

• Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Participants and Legally acceptable representative(s) \[LAR(s)\] who give physical or digital informed consent after the study has been explained according to local regulatory requirements, and before any study-specific procedures are performed. The informed consent given at screening should include consent for both the maternal participant's participation and participation of the infant after the infant's birth.
• Healthy participants as established by medical history and clinical examination at screening.
• Participants between and including 18 and 45 years of age at the time of the study intervention administration (Visit 1/Day 1).
• Pre-pregnancy body mass index (BMI) (based on participant's report) between 17.0 and 39.9 kg/m\^2, inclusive.
• Pregnant female at 27,0/7 to 36,6/7 weeks of gestation (completed week 27 but not week 37) at the time of vaccination (Visit 1/Day 1), as established or confirmed by ultrasound examination.
• No significant fetal abnormalities, as observed by the fetal morphological abnormality screening test conducted after 18 weeks of gestation and the most recent ultrasound testing (no more than 6 weeks before enrollment).
• Nuchal translucency scan, serum testing and any other prenatal tests, if conducted, should suggest normal pregnancy.
• Participants who are willing to provide cord blood and/or infant blood.
• Participants who are willing to have them and their newborns followed-up until 1 month post-delivery.
• Participants who do not plan to give their child for adoption.
• Japanese ethnic origin.

Exclusion criteria

Medical conditions:

• Participants diagnosed with multiple pregnancies.
• Women with co-morbid medical or obstetric conditions that in the opinion of the investigator have the potential to complicate the pregnancy course and outcomes such as;

• Gestational hypertension (defined as systolic blood pressure >=140 mmHg and/or diastolic blood pressure >=90 mmHg) at >=20 weeks of gestation in a woman with a previously normal blood pressure. Women with gestational hypertension who maintain blood pressure in the normal range (<140 mmHg and <90 mmHg) through diet and/or on antihypertensive medications would be eligible except for eclampsia/pre-eclampsia.
• Hemodynamically significant cardiac disorders (previously corrected patent ductus arteriosis is allowed).
• Gestational diabetes which is not controlled by medication, diet and/or exercise as determined by glucose challenge/tolerance test conducted after 20 weeks of gestation or as per local recommendations of the country (Gestational diabetes is defined as absence of pre-gestational diabetes and hyperglycemia during pregnancy, which is not due to other known causes).
• Any other conditions that in the opinion of the investigator have the potential to complicate the pregnancy course and outcomes
• Acute or unstable chronic conditions, chronic clinically significant abnormality, poorly controlled pre-existent co-morbidities or any other clinical conditions, as determined by physical examination and/or laboratory tests.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Recurrent history or uncontrolled neurological disorders or any neuroinflammatory, congenital neurological conditions, encephalopathies, or seizures.
• Condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant and/or to the unborn infant due to participation in the clinical study.
• Prior major congenital anomalies or early onset (<34 weeks of gestation) of eclampsia/pre-eclampsia in previous pregnancy, or stillbirth or neonatal death, or multiple (>=2) spontaneous abortions, or pre-term delivery (<=34 weeks gestation) or having ongoing intervention (medical/surgical) in current pregnancy to prevent pre-term delivery.
• Family history (first degree relatives only) of congenital anomalies, recurrent pregnancy losses (two or more consecutive losses) and unexplained neonatal death(s) in the participant.
• History of an encephalopathy of unknown etiology, occurring within 7 days following previous vaccination with pertussis-containing vaccine.
• History of transient thrombocytopenia or neurological complications (for convulsions or hypotonic-hyporesponsive episodes) following an earlier immunisation against diphtheria and/or tetanus.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention or having shown signs of hypersensitivity after previous administration of diphtheria, tetanus or pertussis vaccines.
• History of physician-diagnosed or laboratory-confirmed pertussis within the past 5 years.
• Lymphoproliferative disorder or malignancy within 5 years before the study dose administration (excluding effectively treated non melanoma skin cancer).

Prior/Concomitant therapy:

• Previous vaccination containing diphtheria, tetanus or pertussis antigens, or diphtheria and tetanus toxoids at any time during the current pregnancy and within 5 years from study participation.
• Use of any investigational or non-registered product other than the study intervention(s) during the current pregnancy or their planned use during the study period.
• Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments or planned administration through delivery.

• Up to 6 months prior to the study intervention administration:

For corticosteroids, this will mean prednisone equivalent >=20 mg/day for adult participants. Inhaled, intra-articular/intra-bursal and topical steroids are allowed.

• Up to 6 months prior to the study intervention administration:

long-acting immune-modifying drugs including among others immunotherapy monoclonal antibodies, antitumoral medication.

• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the dose and planned administration through delivery (Visit 3/Day of delivery), except:

• Seasonal influenza vaccines, RSV vaccines, Hepatitis B vaccines, and SARS-CoV-2, all of which may be administered according to standard of care >=14 days before or after study vaccination.
• Administration of immunoglobulins or other blood products or plasma derivatives during the period starting 3 months before the study intervention or planned administration through delivery with the exception of anti-D (Rh)-immunoglobulin.
• Planned administration of any prophylactic medication (e.g., analgesics, antipyretics) in the absence of any symptom and in anticipation of a reaction to the study intervention administration.

Prior/Concurrent clinical study participation:

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention drug/vaccine/invasive medical device.

Other exclusion criteria:

• History of chronic alcohol consumption and/or drug abuse, based on investigator's judgment.
• Any study personnel or their immediate dependents, family, or household members.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

Japan · 18 centers

• GSK Investigational Site — Chiba
• GSK Investigational Site — Chiba
• GSK Investigational Site — Fukui
• GSK Investigational Site — Fukuoka
• GSK Investigational Site — Fukushima
• GSK Investigational Site — Hokkaido
• GSK Investigational Site — Kanagawa
• GSK Investigational Site — Kyoto
• … and 10 more centers

Identifiers

NCT: NCT07596199 · 308736

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗