A Study of Ad26.COV2.S in Healthy Pregnant Participants (COVID-19)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and reactogenicity of Ad26.COV2.S administered intramuscularly (IM) as a 1-dose schedule at the standard dose level in adult participants during the second and/or third trimester of pregnancy and (potentially) post-partum; to assess the humoral immune response in peripheral blood of adult participants to Ad26.COV2.S administered IM as a 1-dose schedule during the second and/or third trimester of pregnancy, 28 days after vaccination.

Detailed Description
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There is an increased risk of severe coronavirus disease-2019 (COVID-19) during pregnancy, as well as an increased risk of adverse birth outcomes. Therefore, the aim of this study is to assess the safety, reactogenicity and immunogenicity of Ad26.COV2.S in adult participants in the second and/or third trimester of pregnancy. Ad26.COV2.S (also known as Ad26COVS1) is a monovalent vaccine composed of a recombinant, replication incompetent adenovirus type 26 (Ad26) vector, constructed to encode the S protein derived from a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) clinical isolate, stabilized in its prefusion conformation. For each adult participant, the total study duration from screening until the last follow-up visit will be approximately 16 months. The study will consist of a screening phase (28 days), vaccination period (study period from vaccination to pregnancy completion/termination) and a follow-up period (up to 12 months post pregnancy completion/termination). For neonates/infants born to the participants in the study will be followed for approximately 12 months postpartum. Safety assessments will include immunogenicity assessments, physical examination, vital signs, clinical safety laboratory assessments, medical, obstetric and delivery history, pregnancy outcome, neonate safety assessment, adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI).

Official Title
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An Open-label, Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.COV2.S in Healthy Pregnant Participants

Conditions
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COVID-19 Prevention

Intervention / Treatment
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* Biological: Ad26.COV2.S


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: If on medication for a condition, the medication dose must have been stable for at least 4 weeks preceding vaccination Participant must be healthy as confirmed by medical history, physical examination, vital signs, and obstetric history performed at Screening. Participant may have underlying illnesses, as long as the symptoms and signs are medically controlled Participant will be at second or third trimester of pregnancy, that is, Week 16 to Week 38 of gestation (inclusive), at the time of vaccination, based on ultrasound at the time of screening (or not longer than 10 days prior to vaccination if performed elsewhere) Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the last dose of study vaccine Participant must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study Participant either received their last COVID-19 vaccination with an authorized/licensed COVID-19 vaccine (at least 4 months prior to first study vaccination) or is COVID 19 vaccine-naïve Exclusion Criteria: Participants with medical or obstetric histories that put them at higher risk for maternal or fetal complications (example, chronic pregnancy-related disorders, birth defects or genetic conditions during previous pregnancy) Participant with abnormal pregnancy screening test (example, ultrasound fetal abnormalities, maternal blood screen) Participant has a history of malignancy within 2 years before screening (exceptions are squamous, basal cell carcinomas of the skin, carcinoma in situ of the cervix, or malignancy, considered cured with minimal risk of recurrence) Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine) Participant has a history of any serious, chronic, or progressive neurological disorders or seizures including Guillain-Barre syndrome, with the exception of febrile seizures during childhood Participant has a positive diagnostic test result (polymerase chain reaction [PCR] based viral ribonucleic acid [RNA] detection) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection at screening or Day 1 (if more than 4 days in between) Participant has a history of thrombosis with thrombocytopenia syndrome (TTS), including cerebral venous sinus thrombosis (CVST), or heparin-induced thrombocytopenia (HIT) Participant has a history of capillary leak syndrome (CLS)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Groups 1-4: Ad26.COV2.S (One Dose)<br>Participants who are previously vaccinated (Group 1-3) and participants who are vaccine naïve (Group 4) will receive single dose of Ad26.COV2.S vaccine at standard dose level on Day 1. Participants from group 4 who are no longer pregnant may receive single booster dose of Ad26.COV2.S vaccine at standard dose level. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injection of Ad26.COV2.S.<br>* Other names: JNJ-78436735, Ad26COVS1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days After Vaccination or Until Resolution | Solicited local AEs are pre-defined local (at the injection site) AEs for which participants are specifically asked and which are noted by participants in their reactogenicity diary for 7 days post vaccination or until resolution. Solicited local AEs are: injection site pain/tenderness, erythema, swelling at the vaccination site. | 7 days after vaccination or until resolution (Up to Day 8) | 
| Number of Participants with Solicited Systemic AEs for 7 Days After Vaccination or Until Resolution | Participants will be instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) or until resolution for solicited systemic AEs. Solicited systemic events include fatigue, headache, nausea and myalgia. | 7 days after vaccination or until resolution (Up to Day 8) | 
| Number of Participants with Unsolicited AEs | Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant's reactogenicity diary. | 28 days after vaccination (Up to Day 29) | 
| Number of Participants with Serious Adverse Events (SAEs) | SAE is any untoward medical occurrence that at any dose results in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Up to 16 months | 
| Number of Participants with Adverse Events of Special Interest (AESIs) | Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI. | Up to 16 months | 
| Number of Participants with Medically-attended Adverse Events (MAAEs) | MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs. | 6 months after vaccination (Up to Day 183) | 
| Number of Participants with AEs leading to Discontinuation | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to 16 months | 
| Serological Response to Vaccination as Measured by Enzyme-linked Immunosorbent Assay (ELISA) 28 Days After Vaccination | Serological response to vaccination as measured by enzyme-linked immunosorbent assay (S-ELISA, ELISA Units/milliliter [EU/mL]), 28 days after vaccination will be reported. | 28 days after vaccination (Day 29) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group 4: Number of Adult Participants with Solicited Local AEs for 7 Days After Booster Vaccination or Until Resolution | Solicited local AEs are pre-defined local (at the injection site) AEs for which participants are specifically asked and which are noted by participants in their reactogenicity diary for 7 days post booster vaccination or until resolution. Solicited local AEs are: injection site pain/tenderness, erythema, swelling at the vaccination site. | Up to 7 days after booster vaccination or until resolution (up to 16 months) | 
| Group 4: Number of Adult Participants with Solicited Systemic AEs for 7 Days After Booster Vaccination or Until Resolution | Participants will be instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-booster vaccination (Day of booster vaccination and the subsequent 7 days) or until resolution for solicited systemic AEs. Solicited systemic events include fatigue, headache, nausea and myalgia. | Up to 7 days after booster vaccination or until resolution (up to 16 months) | 
| Group 4: Number of Adult Participants with Unsolicited AEs For 28 Days After Booster Vaccination | Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant's reactogenicity diary. | Up to 28 days after booster vaccination | 
| Group 4: Number of Adult Participants with SAEs Throughout the Study (From Booster Vaccination Until End of the Study [EOS]) | SAE is any untoward medical occurrence that at any dose results in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Up to 16 months | 
| Group 4: Number of Adult Participants with AESIs Throughout the Study (From Booster Vaccination Until EOS) | Number of adult participants with AESIs throughout the study (from booster vaccination until EOS) will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI. | Up to 16 months | 
| Group 4: Number of Adult Participants with MAAEs Until 6 Months After Booster Vaccination | MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs. | 6 months after booster vaccination | 
| Number of Adult Participants with AEs leading to Discontinuation (During the Entire Study) | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to 16 months | 
| Number of Adult Participants with Pregnancy Outcomes | Number of adult participants with pregnancy outcomes (including, live term birth, live preterm birth, stillbirth, and abortion) (non-exhaustive) will be reported. | Up to 6 months | 
| Number of Adult Participants with Pregnancy Related AEs | Number of adult participants with pregnancy-related AEs including: gestational diabetes, gestational hypertension, premature rupture of membranes, premature labor, premature uterine contractions, poor or restricted fetal growth, pre-eclampsia, eclampsia, vaginal or intrauterine hemorrhage (non-exhaustive) will be reported. | Up to 6 months | 
| Serological Response to Vaccination as Measured by ELISA and/or Equivalent Assay, at all Blood Collection Timepoints in Adult Participants | Serological response to vaccination as measured by ELISA (S-ELISA, EU/mL) and/or equivalent assay, at all blood collection timepoints in adult participants will be reported. | Up to 16 months | 
| Serological Response to Vaccination as Measured by Virus Neutralization Assay (VNA) Titers, 28 Days After Vaccination in Adult Participants | Serological response to vaccination as measured by VNA titers, 28 days after vaccination in adult participants will be reported. | 28 days after vaccination (Day 29) | 
| Group 4: Serological Response to Booster Vaccination Measured by Binding (S-ELISA and/or Equivalent Assay) in Adult Participants | Serological response to booster vaccination measured by binding (S-ELISA and/or equivalent assay) in adult participants will be reported. | Up to 16 months | 
| Group 4: Serological Response to Booster Vaccination Measured by Neutralizing (VNA) Antibody Titers in Adult Participants | Serological response to booster vaccination measured by neutralizing (VNA) antibody titers in adult participants will be reported | Up to 16 months | 
| Serological Response to Vaccination as Measured by ELISA and/or Equivalent Assay in Infants and Neonates | Serological response to vaccination as measured by ELISA (S-ELISA, EU/mL) and/or equivalent assay will be reported for neonates and infants (born to adult participants who received vaccination) at birth (in cord blood) and up to 2 months and 6 months of age. | From birth up to 2 and 6 months | 
| Serological Response to Vaccination as Measured by VNA Titers at Birth in Neonates and Infants | Serological response to vaccination as measured by VNA titers will be reported for neonates and infants (born to adult participants who received vaccination) at birth (in cord blood). | At birth | 
| Number of Neonates and Infants with SAEs | Number of neonates and infants (born to adult participants who received vaccination) with SAEs including multisystem inflammatory syndrome in children (MIS-C) from birth up to 12 months of age will be reported. | From birth up to 12 months | 
| Number of Neonates and Infants with AESIs | Number of neonates and infants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI. | From birth up to 12 months | 
| Number of Neonates and Infants with MAAEs | Number of neonates and infants (born to adult participants who received vaccination) with MAAEs from birth up to 6 months of age will be reported. | From birth up to 6 months | 
| Number of Neonates and Infants with AEs leading to Study Discontinuation | Number of neonates and infants (born to adult participants who received vaccination) with AEs leading to discontinuation from birth up to 12 months of age will be reported. | From birth up to 12 months | 
| Number of Neonates and Infants with or without any Complications, Anomalies and Deaths | Number of neonates and infants with or without any complication, anomalies and death will be reported. This will also include normal neonate, term neonate with or without complications, preterm neonate with or without complications, neonatal infection, respiratory distress, congenital anomalies, neonatal death, low birth weight, and small for gestational age measured from birth up to 12 months of age (non exhaustive). | From birth up to 12 months |