Clinical trial NCT04535453: A Study to Evaluate a Range of Dose Levels and Vaccination Intervals of Ad26.COV2.S in Healthy Adults and Adolescents
Official title: A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of Dose Levels and Vaccination Intervals of Ad26.COV2.S in Healthy Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years and Older and to Evaluate 2 Dose Levels of Ad26.COV2.S in Healthy Adolescents Aged 12 to 17 Years Inclusive
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
First posted: 2020-09-02
Enrollment: 635
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary purpose of this study is to assess humoral immune responses of 3 dose levels of Ad26.COV2.S administered intramuscularly (IM) as a 2-dose schedule (56 days apart); Ad26.COV2.S administered IM as a single vaccination; safety and reactogenicity of Ad26.COV2.S administered IM as a 2-dose or a single-dose schedule in adults (18-65 years or older) and to assess the safety and reactogenicity of Ad26.COV2.S, administered IM as single dose in adolescents (12-17 years) and to test both compressed and expanded 2-dose schedules of Ad26.COV2.S (28 and 84 days apart) in adults (18-55 years and 65 years or older).

Detailed description: The aim of the COVID-19 vaccine clinical development program is to develop a safe and effective vaccine for the prevention of COVID-19. Currently, there is only limited availability of authorized/licensed vaccines for the prevention of coronavirus disease-2019 (COVID-19). 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 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus spike (S) protein, which will be assessed in this study. Also, different vaccination intervals and multiple lower dose levels compared to the dose levels in the first in human study (VAC31518COV1001 \[NCT04436276\]) will be assessed. For adults, the study consists of: screening phase (28 days), vaccination phase (1-3 months) depending on the vaccination interval, and follow-up (12 months). The study duration is approximately 15 months (Groups 1-6, 8, 10 and Group 7 \[to participants for whom vaccination 2 was delayed\]), 14 months (Group 7), and 16 months (Group 9) in adult groups and approximately 13 months for adolescents group (Groups A to C). The adverse events and other safety assessments including vital signs measurements (heart rate, supine systolic and diastolic blood pressure, respiratory rate, and body temperature), and physical examinations will be assessed during the study.

Note: The Informed Consent Form dated 27-Oct-2020 is final version of the study MASTER ICF, used by local countries to prepare the local language version of the ICF, which have been approved by the Ethics Committees.

And the highlighted text in the ICF document are the guidance for country specific adaptation.

Eligibility criteria: Inclusion Criteria:

For Adults

* Participant must have a body mass index (BMI) less than (\<) 30.0 kilogram per meter square (kg/m\^2)
* Participant is 18 to 55 years of age, inclusive, or 65 years of age or older on the day of signing the informed consent form (ICF).
* Participant 18 to 55 years of age, inclusive: participant must be healthy, in the investigator's clinical judgment, as confirmed by medical history, physical examination, and vital signs performed at screening, and must not have comorbidities related to an increased risk of severe coronavirus disease-2019 (COVID-19), except for smoking and mild hypertension, which are allowed. Participant 65 years of age and older: In the investigator's clinical judgment, participant must be either in good or stable health. Participant may have underlying illnesses, as long as the symptoms and signs are medically controlled and not considered to be comorbidities related to an increased risk of severe COVID-19, except for smoking and mild hypertension, which are allowed. If on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding vaccination and expected to remain stable for the duration of the study. Participant will be included on the basis of physical examination, medical history, and vital signs
* Participant will be included on the basis of physical examination, medical history, and vital signs
* All participants of childbearing potential must: a) Have a negative highly sensitive urine pregnancy test at screening, b)Have a negative highly sensitive urine pregnancy test immediately prior to each study vaccine administration
* 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

For Adolescents:

* Participant is 12 to 17 years of age, inclusive, on the day of signing the informed consent form (ICF)
* Participants must have signed an ICF (or their legally acceptable representative or parent(s) \[preferably both parents if available or as per local requirements\] must sign) indicating that they understand the purpose of, and procedures required for, the study, are willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures, and are willing (or the parents are willing for their adolescent) to participate in the study. Informed assent must be obtained from adolescents, depending on local regulations and practice
* Participant must be healthy, in the investigator's clinical judgment, as confirmed by medical history, physical examination, and vital signs performed at screening, and must not have comorbidities related to an increased risk of severe COVID-19

Exclusion Criteria:

For Adults

* 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 \[C\] (100.4 degree Fahrenheit \[F\]) 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 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 received treatment with immunoglobulins in the 3 months or blood products in the 4 months before the planned administration of the first dose of study vaccine or has any plans to receive such treatment during the study
* Participant received an investigational drug (including investigational drugs for prophylaxis of COVID-19) or used an invasive investigational medical device within 30 days or received investigational Ig or monoclonal antibodies within 3 months, or received convalescent serum for COVID-19 treatment within 4 months or received an investigational vaccine (including investigational Adenoviral-vectored vaccines) within 6 months before the planned administration of the first dose of study vaccine or is currently enrolled or plans to participate in another investigational study during the course of this study For Adolescents
* 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)
* Participants with a history of illness or with an ongoing illness that, in the opinion of the investigator, may pose additional risk to the participant if he/she participates in the study
* Participant has a history of Kawasaki disease
* Participant has a history of an underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Primary outcomes:
measure: Adults of Groups 1, 2 and 3: Percentage of Participants With Serological Response to Vaccination as Measured by Virus Neutralization Assay (VNA) Titers at 28 Days After Vaccination 2
timeFrame: 28 days after Vaccination 2 (Day 85)
measure: Adults of Groups 1, 2 and 3: Percentage of Participants With Serological Response to Vaccination as Measured by Spike Binding Antibodies Enzyme-linked Immunosorbent Assay (S-ELISA) at 28 Days After Vaccination 2
timeFrame: 28 days after Vaccination 2 (Day 85)
measure: Adults of Groups 1, 2 and 3: Antibody Geometric Mean Titers (GMTs) as Measured by VNA at 28 Days After Vaccination 2
timeFrame: 28 days after Vaccination 2 (Day 85)
measure: Adults of Groups 1, 2 and 3: Antibody Geometric Mean Concentrations (GMCs) as Measured by (S-ELISA) at 28 Days After Vaccination 2
timeFrame: 28 days after Vaccination 2 (Day 85)
measure: Adults of Groups 4, 5 and 6: Percentage of Participants With Serological Response to Vaccination as Measured by VNA Titers at 28 Days After Vaccination 1
timeFrame: 28 days after Vaccination 1 (Day 29)
measure: Adults of Groups 4, 5 and 6: Percentage of Participants With Serological Response to Vaccination as Measured by S-ELISA at 28 Days After Vaccination 1
timeFrame: 28 days after Vaccination 1 (Day 29)
measure: Adults of Groups 4, 5 and 6: Antibody GMTs as Measured by VNA at 28 Days After Vaccination 1
timeFrame: 28 days after Vaccination 1 (Day 29)
measure: Adults of Groups 4, 5 and 6: Antibody GMCs as Measured by S-ELISA 28 Days After Vaccination 1
timeFrame: 28 days after Vaccination 1 (Day 29)
measure: Adults of Groups 9 and 10: Percentage of Participants With Serological Response to Vaccination as Measured by VNA Titers 28 Days After Vaccination 2
timeFrame: 28 days after Vaccination 2 ( Day 113)
measure: Adults of Groups 9 and 10: Percentage of Participant With Serological Response to Vaccination as Measured by S-ELISA at 28 Days After Vaccination 2
timeFrame: 28 days after Vaccination 2 (Day 113)
measure: Adults of Groups 9 and 10: Antibody GMTs as Measured by VNA at 28 Days After Vaccination 2
timeFrame: 28 days after Vaccination 2 (Day 113)
measure: Adults of Groups 9 and 10: Antibody GMCs as Measured by S-ELISA at 28 Days After Vaccination 2
timeFrame: 28 Days after Vaccination 2 (Day 113)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Solicited Local Adverse Events (AEs) for 7 Days After Vaccination 1
timeFrame: 7 days after Vaccination 1 (Day 8)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Solicited Systemic Adverse Events (AEs) for 7 Days After Vaccination 1
timeFrame: 7 days after Vaccination 1 (Day 8)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Solicited Local AEs at 7 Days After Vaccination 2
timeFrame: 7 days after Vaccination 2 (Day 64 for Groups 1-6; Day 92 for Groups 9 and 10)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Solicited Systemic AEs at 7 Days After Vaccination 2
timeFrame: 7 days after Vaccination 2 (Day 64 for Group 1-6; Day 92 for Group 9 and 10)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Unsolicited AEs at 28 Days After Vaccination 1
timeFrame: 28 days after Vaccination 1 (Day 29)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Unsolicited AEs at 28 Days After Vaccination 2
timeFrame: 28 days After Vaccination 2 (Day 85 for Groups 1-6; Day 113 for Groups 9 and 10)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to 1.5 years
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: Up to 1.5 years
measure: Adolescents: Number of Participants With Solicited Local AEs at 7 Days After Vaccination 1
timeFrame: 7 Days After Vaccination 1 (Day 8)
measure: Adolescents: Number of Participants With Solicited Systemic AEs at 7 Days After Vaccination 1
timeFrame: 7 Days After Vaccination 1 (Day 8)
measure: Adolescents: Number of Participants With Unsolicited AEs at 28 Days After Vaccination 1
timeFrame: 28 Days After Vaccination 1 (Day 29)
measure: Adolescents: Number of Participants With SAEs (Inclusive Multisystem Inflammatory Syndrome in Children [MIS-C])
timeFrame: Up to unblinding date / receipt of a new Covid vaccine (Up to 1.5 years)
measure: Adolescents: Number of Participants With AESIs
timeFrame: Up to unblinding date / receipt of a new Covid vaccine (Up to 1.5 years)
Secondary outcomes:
measure: Adults of Groups 1 to 5, Groups 7 and 9: Percentage of Participants With Serological Response to Vaccination as Measured by VNA Titers 7 Days After Antigen Presentation
timeFrame: 7 days after antigen presentation (Day 176 for Groups 1-5; Day 148 for Group 7; Day 204 for Group 9)
measure: Adults of Groups 1 to 5, Groups 7 and 9: GMTs as Measured by VNA 7 Days After Antigen Presentation
timeFrame: 7 days after antigen presentation (Day 176 for Groups 1-5; Day 148 for Group 7; Day 204 for Group 9)
measure: Adults of Groups 1 to 5 and Group 9: Percentage of Participants With Serological Response to Vaccination as Measured by S-ELISA 7 Days After Antigen Presentation
timeFrame: 7 Days After Antigen Presentation (Day 176 for Groups 1-5 ; Day 204 for Group 9)
measure: Adults of Group 7: Percentage of Participants With Serological Response to Vaccination as Measured by S-ELISA 7 Days After Antigen Presentation
timeFrame: Day 148
measure: Adults of Groups 1 to 5 and Group 9: Antibody GMCs as Measured by S-ELISA 7 Days After Antigen Presentation
timeFrame: 7 Days after Antigen Presentation (Day 176 for Groups 1-5; Day 204 for Group 9)
measure: Adults of Group 7: Antibody GMCs as Measured by S-ELISA 7 Days After Antigen Presentation
timeFrame: Day 148
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Solicited Local AEs at 7 Days After Antigen Presentation
timeFrame: 7 Days After Antigen Presentation (Day 176 for Groups 2-5, Groups 1 and 7 combined, Groups 6 and 8 combined; Day 204 for Group 9 and 10)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Solicited Systemic AEs at 7 Days After Antigen Presentation
timeFrame: 7 Days After Antigen Presentation (Day 176 for Groups 2-5, Groups 1 and 7 combined, Groups 6 and 8 combined; Day 204 for Group 9 and 10)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With Unsolicited AEs at 28 Days After Antigen Presentation
timeFrame: 28 Days After Antigen Presentation (Day 197 for Groups 2-5, Groups 1 and 7 combined, Groups 6 and 8 combined; Day 225 for Group 9 and 10)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With SAEs After Antigen Presentation
timeFrame: After antigen presentation until end of study (Day 170 up to 1.5 years for Groups 2-5, Groups 1 and 7 combined, Groups 6 and 8 combined; Day 198 up to 1.5 years for Group 9 and 10)
measure: Adults of Groups 2 to 5, Group 9-10, 1 and 7 Combined, 6 and 8 Combined: Number of Participants With AESIs After Antigen Presentation
timeFrame: After antigen presentation until end of study (Day 170 up to 1.5 years for Groups 2-5, Groups 1 and 7 combined, Groups 6 and 8 combined; Day 198 up to 1.5 years for Group 9 and 10)
measure: Adults Groups 1 to 6: Percentage of Participants With Neutralizing Antibody Titers to the Wild-type SARS-CoV-2 Virus Expressing S-protein as Measured by VNA
timeFrame: Days 197 and 393
measure: Adults Group 9 and 10: Percentage of Participants With Neutralizing Antibody Titers to the Wild-type SARS-CoV-2 Virus Expressing S-protein as Measured by VNA
timeFrame: Days 225 and 421
measure: Adults Groups 1 to 6: Percentage of Participants With Binding Antibody Titers to SARS-CoV-2 or Individual SARS-CoV-2 Proteins
timeFrame: Days 197 and 393
measure: Adults of Groups 9 and 10: Percentage of Participants With Binding Antibody Titers to SARS-CoV-2 or Individual SARS-CoV-2 Proteins
timeFrame: Days 225 and 421
measure: Adolescents: Percentage of Participants With Serological Response to Vaccination as Measured by VNA Titers 28 Days After Vaccination 1 (Day 29)
timeFrame: 28 Days After Vaccination 1 (Day 29)
measure: Adolescents: Percentage of Participants With Serological Response to Vaccination as Measured by S-ELISA 28 Days After Vaccination 1 (Day 29)
timeFrame: 28 Days After Vaccination 1 (Day 29)
measure: Adolescents: Antibody GMTs as Measured by VNA at 28 Days After Vaccination 1
timeFrame: 28 days After Vaccination 1 (Day 29)
measure: Adolescents: Antibody GMCs as Measured by S-ELISA 28 Days After Vaccination 1
timeFrame: 28 days After Vaccination 1 (Day 29)
measure: Adolescents: Neutralizing Antibody Titers to the Wild-type SARS-CoV-2 Virus Expressing S Protein as Measured by VNA
timeFrame: Days 57, 85 and 169
measure: Adolescents: Binding Antibody Titers to SARS-CoV-2 or Individual SARS-CoV-2 Proteins as Measured by ELISA
timeFrame: Days 57, 85, 169
measure: Adults: Percentage of Participants With Serological Response to Vaccination as Measured by S-ELISA 7 Days After Antigen Presentation
timeFrame: 7 Days After Antigen Presentation (Day 176 for Groups 1-5 ; Day 204 for Group 9)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH
city: Hamburg
country: Germany
facility: CTC North GmbH & Co. KG, Am Universitätsklinikum Hamburg-Eppendorf
city: Rostock
country: Germany
facility: Universitaetsmedizin Rostock
city: Groningen
country: Netherlands
facility: PRA Health Sciences
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
city: Utrecht
country: Netherlands
facility: UMCU
city: Madrid
country: Spain
facility: Hosp. Univ. de La Princesa
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Liverpool
country: United Kingdom
facility: Alder Hey Hospital
city: London
country: United Kingdom
facility: St George's, University of London
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Sadoff J, Le Gars M, Brandenburg B, Cardenas V, Shukarev G, Vaissiere N, Heerwegh D, Truyers C, de Groot AM, Jongeneelen M, Kaszas K, Tolboom J, Scheper G, Hendriks J, Ruiz-Guinazu J, Struyf F, Van Hoof J, Douoguih M, Schuitemaker H. Durable antibody responses elicited by 1 dose of Ad26.COV2.S and substantial increase after boosting: 2 randomized clinical trials. Vaccine. 2022 Jul 30;40(32):4403-4411. doi: 10.1016/j.vaccine.2022.05.047. Epub 2022 Jun 3.