Clinical trial NCT04765384: A Study of Ad26.COV2.S in Healthy Pregnant Participants (COVID-19)
Official title: An Open-label, Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.COV2.S in Healthy Pregnant Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19 Prevention
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
First posted: 2021-02-21
Enrollment: 51
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

Detailed 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).

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Adult Participants With Solicited Local Adverse Events (AEs) for 7 Days Post First Vaccination
timeFrame: From first vaccination on Day 1 up to 7 days post first vaccination (up to Day 8)
measure: Number of Adult Participants With Solicited Systemic AEs for 7 Days Post First Vaccination
timeFrame: From first vaccination on Day 1 up to 7 days post first vaccination (up to Day 8)
measure: Number of Adult Participants With Unsolicited AEs for 28 Days Post First Vaccination
timeFrame: From first vaccination on Day 1 up to 28 days post first vaccination (up to Day 29)
measure: Number of Adult Participants With Serious Adverse Events (SAEs) From First Vaccination Until End of the Study (EOS)
timeFrame: From first vaccination on Day 1 until end of study (up to post-partum [PP] Day 366 [Day 15 up to Day 554])
measure: Number of Adult Participants With Adverse Events of Special Interest (AESIs) From First Vaccination Until EOS
timeFrame: From first vaccination on Day 1 until end of study (up to PP Day 366 [Day 15 up to Day 554])
measure: Number of Adult Participants With Medically Attended Adverse Events (MAAEs) Until 6 Months Post First Vaccination
timeFrame: From first vaccination on Day 1 until 6 months post first vaccination (up to Day 183)
measure: Number of Adult Participants With AEs Leading to Study Discontinuation
timeFrame: From first vaccination on Day 1 until end of study (up to PP Day 366 [Day 15 up to Day 554])
measure: Serological Response to Vaccination as Measured by S-Enzyme-linked Immunosorbent Assay (S-ELISA) in Adult Participants 28 Days Post First Vaccination
timeFrame: 28 days post first vaccination on Day 1 (at Day 29)
Secondary outcomes:
measure: Group 4: Number of Adult Participants With Solicited Local AEs for 7 Days Post Booster Vaccination
timeFrame: 7 days post booster vaccination (Day 84 up to Day 371)
measure: Group 4: Number of Adult Participants With Solicited Systemic AEs for 7 Days Post Booster Vaccination
timeFrame: 7 days post booster vaccination (Day 84 up to Day 371)
measure: Group 4: Number of Adult Participants With Unsolicited AEs for 28 Days Post Booster Vaccination
timeFrame: 28 days post booster vaccination (Day 84 up to Day 392)
measure: Group 4: Number of Adult Participants With SAEs Post Booster Vaccination Until EOS
timeFrame: From booster vaccination (Day 84 up to Day 364) until EOS (up to PP Day 366 [Day 366 up to Day 554])
measure: Group 4: Number of Adult Participants With AESIs Post Booster Vaccination Until EOS
timeFrame: From booster vaccination (Day 84 up to Day 364) until EOS (up to PP Day 366 [Day 366 up to Day 554])
measure: Group 4: Number of Adult Participants With MAAEs Until 6 Months Post Booster Vaccination
timeFrame: 6 months post booster vaccination (Day 84 up to Day 546)
measure: Group 4: Number of Adult Participants With AEs Leading to Study Discontinuation Post Booster Vaccination Until EOS
timeFrame: From post booster vaccination (Day 84 up to Day 364) until EOS (up to PP Day 366 [Day 366 up to Day 554])
measure: Number of Adult Participants With Pregnancy Outcomes
timeFrame: From first vaccination on Day 1 until PP Day 1 (Day 7 up to Day 163)
measure: Number of Adult Participants With Pregnancy Related AEs Throughout Pregnancy
timeFrame: From first vaccination on Day 1 until PP Day 1 (Day 7 up to Day 163)
measure: Serological Response to First Vaccination as Measured by S-ELISA in Adult Participants at All Blood Collection Timepoints Post First Vaccination
timeFrame: Day 1, Day 29, PP Day 1 (Day 7 up to Day 163), PP Day 183 (Day 189 up to Day 345)
measure: Serological Response to First Vaccination as Measured by Virus Neutralization Assay (VNA) Titers, 28 Days in Adult Participants Post First Vaccination
timeFrame: 28 days post first vaccination on Day 1 (at Day 29)
measure: Group 4: Serological Response to Booster Vaccination Measured by Binding (S-ELISA) Antibody Titers in Adult Participants at Blood Collection Time Points Post Booster Vaccination
timeFrame: Booster Day 1 (Day 84 up to Day 364), Booster Day 29 (Day 112 up to Day 392)
measure: Group 4: Serological Response to Booster Vaccination Measured by Neutralizing (VNA) Antibody Titers in Adult Participants at Blood Collection Time Points Post Booster Vaccination
timeFrame: Booster Day 1 (Day 84 up to Day 364), Booster Day 29 (Day 112 up to Day 392)
measure: Serological Response to Vaccination as Measured by S-ELISA at Birth (That is, in Cord Blood) and at 2 Months and 6 Months of Age in Neonates and Infants Born to Adult Participants
timeFrame: At birth (postnatal [PN] Day 1 [Day 7 up to Day 163]), 2 months (up to PN Day 61 [Day 67 up to Day 223]) and 6 months (up to PN Day 183 [Day 189 up to Day 345])
measure: Serological Response to Vaccination as Measured by VNA Titers at Birth (That is, in Cord Blood) in Neonates and Infants Born to Adult Participants
timeFrame: At Birth (PN Day 1 [Day 7 up to Day 163])
measure: Number of Neonates and Infants With SAEs (Including MIS-C) From Birth Up to 12 Months of Age in Neonates and Infants Born to Adult Participants
timeFrame: From birth (PN Day 1 [Day 7 up to Day 163]) up to 12 months of age (up to PN Day 366 [Day 372 up to Day 528])
measure: Number of Neonates and Infants With AESIs From Birth Until 12 Months of Age in Neonates and Infants Born to Adult Participants
timeFrame: From birth (PN Day 1 [Day 7 up to Day 163]) until 12 months of age (up to PN Day 366 [Day 372 up to Day 528])
measure: Number of Neonates and Infants With MAAEs From Birth Until 6 Months of Age in Neonates and Infants Born to Adult Participants
timeFrame: From birth (PN Day 1 [Day 7 up to Day 163]) until 6 months of age (up to PN 183 [Day 189 up to Day 345])
measure: Number of Neonates and Infants With AEs Leading to Study Discontinuation From Birth Until Study Discontinuation
timeFrame: From birth (PN Day 1 [Day 7 up to Day 163]) until study discontinuation (until 12 months of age [up to PN Day 366 {Day 372 up to Day 528}])
measure: Number of Neonates and Infants With Different Birth Outcomes From Birth Up to 12 Months of Age
timeFrame: From birth (PN Day 1 [Day 7 up to Day 163]) up to 12 months of age (up to PN Day 366 [Day 372 up to Day 528])
Other outcomes:
Locations:
city: Gulfport
country: United States
facility: Medpharmics, LLC
state: Mississippi
city: Norfolk
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Albuquerque
country: United States
facility: Medpharmics, LLC
state: New Mexico
city: League City
country: United States
facility: Maximos OB/GYN
state: Texas
city: Belo Horizonte
country: Brazil
facility: Universidade Federal De Minas Gerais - Hospital das Clínicas
city: Criciúma
country: Brazil
facility: Sociedade Literaria e Caritativa Santo Agostinho Hospital Sao Jose
city: Marilia
country: Brazil
facility: Associacaode Ensino de Marilia LTDA - UNIMAR - Universidade de Marilia
city: Natal
country: Brazil
facility: Centro de Estudos e Pesquisas em Moléstias Infecciosas - CEPCLIN
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
city: Porto Alegre
country: Brazil
facility: NPCRS Nucleo de Pesquisa Clinica do Rio Grande do Sul
city: Sao Bernardo do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base
city: Sorocaba
country: Brazil
facility: CMPC - Consultoria Médica e Pesquisa Clínica
city: São Paulo
country: Brazil
facility: Clinical Research College
city: Dennilton
country: South Africa
facility: Ndlovu Elandsdoorn Site
city: Johannesburg
country: South Africa
facility: Shandukani Research Centre
city: Mamelodi East
country: South Africa
facility: Stanza Clinical Research Centre : Mamelodi
city: Soweto
country: South Africa
facility: Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References: