A Study of Ad26.COV2.S in Adults (COVID-19)

Covid-19 Prevention Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26COVS1 in Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years and Older

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04436276
• Other study ID #: CR108828
• Secondary ID: 2020-001483-28VA
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 15, 2020
• Est. completion date: February 21, 2023

Study information

• Verified date: May 2023
• Source: Janssen Vaccines & Prevention B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to assess the safety, reactogenicity, and immunogenicity of Ad26.COV2.S at 2 dose levels, administered intramuscularly (IM) as a single-dose or 2-dose schedule, with a single booster vaccination administered in one cohort in healthy adults aged greater than or equal to (>=) 18 to less than or equal to (<=) 55 years and in adults aged >= 65 years in good health with or without stable underlying conditions. The purpose of the study is also to assess the safety and reactogenicity of Ad26.COV2.S administered as ad hoc booster vaccination in healthy adults aged >= 18 to <= 55 years and in adults >= 65 years in good health with or without stable underlying conditions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1085
• Est. completion date: February 21, 2023
• Est. primary completion date: February 21, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose, procedures, and potential risks and benefits of the study, and is willing to participate in the study
• All female participants of childbearing potential must have a negative highly sensitive urine pregnancy test at screening; and have a negative highly sensitive urine pregnancy test immediately prior to each study vaccine administration
• Participant must have a body mass index (BMI) less than or equal to (<=) 30.0 kilograms per square meter (kg/m^2)
• Applicable to Cohorts 1 and 2 only: Participant must be healthy, in the investigator's clinical judgment, as confirmed by medical history, physical examination, clinical laboratory assessments, and vital signs performed at screening, and must not have comorbidities related to an increased risk of severe coronavirus disease-2019 (COVID-19). Applicable to Cohort 3 only: In the investigator's clinical judgment, participant must be either in good or stable health Participants may have underlying illnesses such as hyperlipoproteinemia or hypothyroidism, as long as their symptoms and signs are medically controlled and not considered to be comorbidities related to an increased risk of severe COVID-19 (participants may have medical conditions of mild severity (according to the Toxicity Grading Scale), as long as it is stable and medically controlled as defined by no change in medication over the past 6 months (except for issues of tolerability or use of similar drug with same mechanism of action, for example, thiazides, Beta blockers, Alpha blockers at the same effective dose).

Exclusion criteria:

• Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0 degree Celsius within 24 hours prior to the planned first dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor
• Participant has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
• Participant has a history of any neurological disorders or seizures including Guillain-Barre syndrome, with the exception of febrile seizures during childhood
• Participant has a positive diagnostic test result for SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) at screening
• Participants with comorbidities that are or might be associated with an increased risk of progression to severe COVID-19, that is, participants with moderate-to-severe asthma; chronic lung diseases such as chronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis), idiopathic pulmonary fibrosis and cystic fibrosis; diabetes (including type 1 or type 2); serious heart conditions, including heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and (pulmonary) hypertension or high blood pressure; obesity (BMI >= 30 kg/m^2); chronic liver disease, including cirrhosis; sickle cell disease; thalassemia; cerebrovascular disease; neurologic conditions (dementia); smoking end stage renal disease; organ transplantation; cancer; HIV infection and other immunodeficiencies; hepatitis B infection; and sleep apnea. Applicable to Cohort 3 only: Participants may have hypertension of mild severity (according to the Toxicity Grading Scale), as long as it is stable and medically controlled as defined by no change in medication over the past 6 months (except for issues of tolerability or use of similar drug with same mechanism of action, for example, thiazides, Beta blockers, Alpha blockers at the same effective dose)
• Applicable to Cohorts 1 and 3 only: Participant currently working in an occupation with a high risk of exposure to SARS-CoV-2 (for example, health care worker or emergency response personnel) or considered at the investigator's discretion to be at increased risk to acquire COVID-19 for any other reason

Related Conditions & MeSH terms

• COVID-19
• Covid-19 Prevention

Intervention

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

Locations

Country	Name	City	State
Belgium	Universiteit Antwerpen - Centrum voor de Evaluatie van Vaccinaties (CEV)	Edegem
Belgium	UZA-SGS	Edegem
Belgium	Center for Vaccinology (CEVAC)	Gent
Belgium	UZ Leuven	Leuven
Belgium	Clinical Pharmacology Unit	Merksem
United States	Optimal Research	Austin	Texas
United States	Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	AMR New Orleans, Formerly New Orleans Center for Clinical Research - New Orleans, an AMR company	Knoxville	Tennessee
United States	Optimal Research	Melbourne	Florida
United States	Optimal Research	Peoria	Illinois
United States	Optimal Research	Rockville	Maryland
United States	Optimal Research	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Vaccines & Prevention B.V.

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after First Vaccination	Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after first vaccination. Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.	Day 8 (7 Days after first vaccination on Day 1)
Primary	Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after Second Vaccination	Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after second vaccination. Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.	Day 64 (7 Days after second vaccination on Day 57)
Primary	Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after First Vaccination	Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after first vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia.	Day 8 (7 Days after first vaccination on Day 1)
Primary	Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after Second Vaccination	Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after second vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia.	Day 64 (7 Days after second vaccination on Day 57)
Primary	Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after First Vaccination	Number of participants with unsolicited AEs for 28 days after first vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.	Day 29 (28 Days after first vaccination on Day1)
Primary	Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after Second Vaccination	Number of participants with unsolicited AEs for 28 days after second vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.	Day 85 (28 Days after second vaccination)
Primary	Cohorts 1 and 3: Number of Participants with Serious Adverse Events (SAEs) from the First Vaccination until 2 Years after the Second Vaccination	SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: 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.	Day 1 (vaccination 1) up to 2 years after second vaccination (up to Day 787)
Primary	Cohort 2: Number of Participants with SAEs from the First Vaccination until 6 Months after the First Vaccination	SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: 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.	Day 1 (vaccination 1) up to 6 Months
Primary	Cohort 2: Number of Participants with SAEs from the First Vaccination until 6 Months after the Second Vaccination	SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: 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.	Day 1 (vaccination 1) up to 6 months after second vaccination (Day 239)
Primary	Cohorts 1 and 3: Number of Participants with Adverse Events of Special Interest (AESIs) from the First Vaccination until 2 Years after the Second Vaccination	Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI.	Day 1 (vaccination 1) up to 2 year after second vaccination (up to Day 787)
Primary	Cohort 2: Number of Participants with AESIs from the First Vaccination until 6 Months after the First Vaccination	Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI.	Day 1 (vaccination 1) up to 6 Months
Primary	Cohort 2: Number of Participants with AESIs from the First Vaccination until 6 Months after the Second Vaccination	Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI.	Day 1 (vaccination 1) up to 6 months after second vaccination (Day 239)
Primary	Number of Participants with Solicited Local AEs for 7 Days after ad hoc Booster Vaccination	Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after ad hoc vaccination. Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site.	Up to 7 days after ad hoc booster vaccination
Primary	Number of Participants with Solicited Systemic AEs for 7 Days after ad hoc Booster Vaccination	Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after ad hoc booster vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia.	Up to 7 days after ad hoc booster vaccination
Primary	Number of Participants with Unsolicited AEs for 28 Days after ad hoc Booster Vaccination	Number of participants with unsolicited AEs for 28 days after ad hoc booster vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.	Up to 28 days after ad hoc booster vaccination
Primary	Number of Participants with SAEs from ad hoc Booster Vaccination Until the end of the Study	SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: 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.	from ad hoc booster vaccination (greater or equal to [>=] 6 months after last Covid-19 vaccination [within 120 days]) to end of study (up to 38 months)
Primary	Number of Participants with AESIs from ad hoc Booster Vaccination Until the end of the Study	Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI.	from ad hoc booster vaccination (>= 6 months after last Covid-19 vaccination [within 120 days]) to end of study (up to 38 months)
Secondary	Cohorts 1, 2, and 3: Number of Participants With SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA)	Number of participants with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported.	Up to 38 Months
Secondary	Cohorts 1, 2, and 3: Number of Participants with SARS-CoV-2 Binding Antibodies Assessed by ELISA	Number of participants with SARS-CoV-2 binding antibodies as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response will be reported.	Up to 38 Months
Secondary	Cohorts 1, 2, and 3: Number of Participants with T-helper (Th)-1 and Th-2 Immune Responses as Assessed by Flow Cytometry	Number of participants with Th-1 and Th-2 immune responses will be reported. Th1 and Th2 immune responses will be assessed by flow cytometry after SARS-CoV-2 S protein peptide stimulation of peripheral blood mononuclear cells (PBMCs) and intracellular staining [ICS] including cluster of differentiation (CD)-4+/CD-8+, Interferons (INF)-gamma, interleukin [IL] 2, Tumor Necrosis Factor (TNF)-alpha, IL-4, IL-5, IL-13, and/or other Th-1/Th-2 markers.	Up to 38 Months
Secondary	Platelet Count in Participants on the day of ad hoc Booster Vaccination and 28 days After ad hoc Booster Vaccination	Platelet count in participants on the day of ad hoc booster vaccination and 28 days after ad hoc booster vaccination will be reported.	On the day of ad hoc booster vaccination and up to 28 days after ad hoc booster vaccination
Secondary	Number of Participants with Normal or Abnormal Results Based on Additional Analysis on Collected Sera Samples in Case of Potential Thromboembolic Events	Number of participants with normal or abnormal results based on additional analysis (including, but not limited to Activated partial thromboplastin time, Prothrombin time, International normalized ratio, Fibrinogen, D-dimer, Lupus anticoagulant, Anti-cardiolipin antibody, Beta-2 glycoprotein, Heparin Induced Thrombocytopenia (HIT)/PF4 antibody Immunoglobulin G (Ab,IgG)(HIT assay), Platelet activation assay (if HIT/PF4 is positive), Homocysteine, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13 Activity and Inhibitor Profile) on collected sera samples in case of reported potential thromboembolic events.	On the day of ad hoc booster vaccination and up to 28 days after ad hoc booster vaccination