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

COVID-19 Prevention Clinical Trial

— HORIZON 1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04765384
• Other study ID #: CR108962
• Secondary ID: 2020-005330-14VA
• Status: Completed
• Phase: Phase 2
• Start date: August 27, 2021
• Est. completion date: November 24, 2023

Study information

• Verified date: February 2024
• Source: Janssen Vaccines & Prevention B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: November 24, 2023
• Est. primary completion date: November 24, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Prevention

Intervention

Biological:
• Ad26.COV2.S
Participants will receive intramuscular (IM) injection of Ad26.COV2.S.

Locations

Country	Name	City	State
Brazil	Universidade Federal De Minas Gerais - Hospital das Clínicas	Belo Horizonte
Brazil	Sociedade Literaria e Caritativa Santo Agostinho - Hospital Sao Jose	Criciúma
Brazil	Associacaode Ensino de Marilia LTDA - UNIMAR - Universidade de Marilia	Marilia
Brazil	Centro de Estudos e Pesquisas em Moléstias Infecciosas - CEPCLIN	Natal
Brazil	Hospital das Clinicas de Porto Alegre	Porto Alegre
Brazil	NPCRS Nucleo de Pesquisa Clinica do Rio Grande do Sul	Porto Alegre
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clínicos	Sao Bernardo do Campo
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base	Sao Jose do Rio Preto
Brazil	Clinical Research College	São Paulo
Brazil	CMPC - Consultoria Médica e Pesquisa Clínica	Sorocaba
South Africa	Ndlovu Elandsdoorn Site	Dennilton
South Africa	Shandukani Research Centre	Johannesburg
South Africa	Stanza Clinical Research Centre : Mamelodi	Mamelodi East
South Africa	Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital	Soweto
United States	Medpharmics, LLC	Albuquerque	New Mexico
United States	Medpharmics, LLC	Gulfport	Mississippi
United States	Maximos OB/GYN	League City	Texas
United States	Meridian Clinical Research, LLC	Norfolk	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Vaccines & Prevention B.V.

Countries where clinical trial is conducted

United States,  Brazil,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	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
Primary	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)
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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