A Study to Evaluate Different Dose Levels of Ad26.COV2.S in Healthy Adolescents From 12 to 17 Years Inclusive

Phase 2

Completed

Conditions: Coronavirus Disease-2019 (COVID-19) Prevention

Interventions: Biological: Ad26.COV2.S

Registration Number: NCT05007080

Lead Sponsor: Janssen Vaccines & Prevention B.V.

Brief Summary: The primary purpose of this study is to assess the safety, reactogenicity, and humoral immune response of Ad26.COV2.S administered intramuscularly (IM) as a 1-dose schedule or as a 2-dose schedule (56-day interval) in adolescents.

Detailed Description: Available safety, immunogenicity and efficacy data from the Ad26.COV2.S vaccine development program supports initiating evaluation of Ad26.COV2.S in the pediatric population. Ad26.COV2.S will be evaluated in the pediatric population through a dose-confirmation approach. Ad26.COV2.S (also known as Ad26COVS1, VAC31518, JNJ-78436735) is a monovalent vaccine composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector, constructed to encode the severe acute respiratory syndrome coronavirus(-2) (SARS-CoV-2) spike (S) protein, stabilized in its prefusion conformation. The study duration from screening until the last follow-up visit will be, excluding the 28-day screening phase, 8 months (Groups 4-6) to 12 months (Groups 1-3), consisting of 12-month study duration comprising a study period (6-months) including vaccination with a 1 active dose and a placebo vaccination (56-day interval), followed by a booster vaccination at 6 months and follow-up (safety and immunogenicity) until at least 6 months after booster vaccination (Groups 1-3) and 8 month study duration comprising 2 active doses (56-day interval) and follow-up (safety and immunogenicity) until at least 6 months after second vaccination (Groups 4-6). Assessments like immunogenicity (such as humoral and cellular immune responses), safety and reactogenicity (such as adverse events \[AEs\] monitoring) will be performed in this study. Other safety assessments include vital signs measurements (heart rate, supine systolic and diastolic blood pressure, respiratory rate, and body temperature) and physical examinations. The overall study duration from enrolment of the first participant until study completion is expected to be up to 1 year 11 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 304

Inclusion Criteria

Participant's age is 12 to 17 years of age at the time of first vaccination
Participant must be healthy, in the investigator's clinical judgement, 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)
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 and/or parent(s)/legal guardian(s) are available and willing to participate for the duration of the study visits and follow-up
Each participant or participant's parent(s)/legal guardian(s) must have access to a consistent means of contact either by telephone contact or email/computer

Exclusion Criteria

Participant has a history of malignancy, bone marrow transplant, or solid organ transplant within 5 years before screening
Participant has a known or suspected allergy, history of anaphylaxis, or other serious adverse reactions, related to vaccines or their excipients (including specifically the excipients of the study vaccine)
Use of systemic corticosteroids at an immunosuppressive dose (treatment duration more than 14 days for one course or recurrent use) within 6 months before administration of study vaccine and during the study
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
Any serious, chronic, or progressive disease (example: diabetes, cardiac disease, hepatic disease, progressive neurological disease or seizure disorder; autoimmune disease, acquired immunodeficiency syndrome [AIDS] infection, blood dyscrasias, bleeding diathesis, signs of cardiac or renal failure, or severe malnutrition)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 4: Ad26.COV2.S Dose Level 1: 2-Dose Regimen	Ad26.COV2.S	Participants will receive 2-dose of Ad26.COV2.S at dose level 1 on Day 1 and 57. Participants will be unblinded to the primary vaccination regimen at 6 months after the first vaccination.
Group 5: Ad26.COV2.S Dose Level 2: 2-Dose Regimen	Ad26.COV2.S	Participants will receive 2-doses of Ad26.COV2.S at dose level 2 on Day 1 and Day 57. Participants will be unblinded to the primary vaccination regimen at 6 months after the first vaccination.
Group 3: Ad26.COV2.S Dose Level 3: 1-Dose Regimen	Ad26.COV2.S	Participants will receive 1-dose of Ad26.COV2.S at dose level 3 on Day 1 and placebo on Day 57. Participants will be unblinded to the primary vaccination regimen at 6 months after the first vaccination. Participants will receive booster vaccination at dose level 1 on Day 184.
Group 1: Ad26.COV2.S Dose Level 1 (Lower Volume): 1-Dose Regimen	Ad26.COV2.S	Participants will receive 1-dose of Ad26.COV2.S at dose level 1 on Day 1 and placebo on Day 57. Participants will be unblinded to the primary vaccination regimen at 6 months after the first vaccination. Participants will receive booster vaccination at dose level 1 on Day 184.
Group 2: Ad26.COV2.S Dose Level 2: 1-Dose Regimen	Ad26.COV2.S	Participants will receive 1-dose of Ad26.COV2.S at dose level 2 on Day 1 and placebo on Day 57. Participants will be unblinded to the primary vaccination regimen at 6 months after the first vaccination. Participants will receive booster vaccination at dose level 1 on Day 184.
Group 6: Ad26.COV2.S Dose Level 3: 2-Dose Regimen	Ad26.COV2.S	Participants will receive 2-doses of Ad26.COV2.S at dose level 3 on Day 1 and Day 57. Participants will be unblinded to the primary vaccination regimen at 6 months after the first vaccination.

Primary Outcome Measures

Name	Time	Method
Groups 1, 2, 3, 4, 5 and 6: Number of Participants With Solicited Local Adverse Events (AEs) at 7 Days Post-dose 1	7 days post-dose 1 on Day 1 (Day 8)	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. Solicited AEs were used to assess the reactogenicity of the study vaccine and were pre-defined as local (at the injection site) AEs for which participants were specifically asked and which were noted by participants in their reactogenicity diary for 7 days post each vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, swelling at the vaccination site.
Groups 1, 2, 3, 4, 5 and 6: Number of Participants With Solicited Systemic AEs at 7 Days Post-dose 1	7 days post-dose 1 on Day 1 (Day 8)	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. Solicited AEs were used to assess the reactogenicity of the study vaccine and were predefined as systemic AES for which participants were specifically asked and which were noted by participants in their reactogenicity diary for 7 days post each vaccination. Participants were 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) for the following solicited systemic AEs: fatigue, headache, nausea, myalgia and pyrexia.
Groups 1, 2, 3, 4, 5 and 6: Number of Participants With Solicited Systemic AEs at 7 Days Post-dose 2	7 days post-dose 2 on Day 57 (Day 64)	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. Solicited AEs were used to assess the reactogenicity of the study vaccine and were predefined as systemic AES for which participants were specifically asked and which were noted by participants in their reactogenicity diary for 7 days post each vaccination. Participants were 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) for the following solicited systemic AEs: fatigue, headache, nausea, myalgia and pyrexia.
Groups 1, 2, 3, 4, 5 and 6: Number of Participants With Unsolicited AEs at 28 Days Post-dose 2	28 days post-dose 2 on Day 57 (Day 85)	Description: 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. Solicited AEs that started within 7 days after vaccination but were ongoing after this 7-day window after each vaccination are also considered unsolicited AEs. Unsolicited AEs were defined as AEs for which the participants were not specifically questioned in the participant's reactogenicity diary.
Groups 1, 2, 3, 4, 5 and 6: Number of Participants With MAAEs 6 Months Post-Dose 2	From the first vaccination (Day 1) until 6 months post-dose 2 on Day 57 (Up to Day 240)	MAAEs were 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 were not be considered medically-attended visits. New onset of chronic diseases were collected as part of the MAAEs.
Groups 1, 2, 3, 4, 5 and 6: Number of Participants With Solicited Local Adverse Events (AEs) at 7 Days Post-dose 2	7 days post-dose 2 on Day 57 (Day 64)	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. Solicited AEs were used to assess the reactogenicity of the study vaccine and were pre-defined as local (at the injection site) AEs for which participants were specifically asked and which were noted by participants in their reactogenicity diary for 7 days post each vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, swelling at the vaccination site.
Groups 1, 2, 3, 4, 5 and 6: Number of Participants With Unsolicited AEs at 28 Days Post-dose 1	28 days post-dose 1 on Day 1 (Day 29)	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. Solicited AEs that started within 7 days after vaccination but were ongoing after this 7-day window after each vaccination are also considered unsolicited AEs. Unsolicited AEs were defined as AEs for which the participants were not specifically questioned in the participant's reactogenicity diary.
Groups 1, 2, 3, 4, 5 and 6: Serological Response to Vaccination Measured by Virus Neutralization Assay (VNA) Titers 28 Days Post-dose 1	28 days post-dose 1 on Day 1 (Day 29)	Serological response to vaccination measured by VNA titers at 28 days post-dose 1 were reported. For Vaccine-specific responses, a participant was defined as a responder if: 1. a baseline sample value of \<=LLOQ and a postbaseline sample strictly greater than the LLOQ; or 2. a baseline sample value strictly \>LLOQ and a postbaseline sample value representing an at least 4-fold increase from the baseline sample value, was reported. Data were expressed as 50 percent (%) inhibitory concentration (IC50) units.
Serological Response to Vaccination Measured by VNA Titers 14 Days Post-dose 2	14 days post-dose 2 on Day 57 (Day 71)	Serological response to vaccination measured by VNA titers 14 days post-dose 2 were reported. For Vaccine-specific responses, a participant was defined as a responder if: 1. a baseline sample value of \<=LLOQ and a postbaseline sample strictly greater than the LLOQ; or 2. a baseline sample value strictly \>LLOQ and a postbaseline sample value representing an at least 4-fold increase from the baseline sample value, was reported. Data were expressed as IC50 units.
Groups 1, 2, 3, 4, and 5: Number of Participants With Medically-attended Adverse Events (MAAEs) 6 Months Post-Dose 1	From the first vaccination (Day 1) until 6 months post-dose 1 on Day 1 (Up to Day 184)	MAAEs were 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 were not be considered medically-attended visits. New onset of chronic diseases were collected as part of the MAAEs.
Groups 1, 2, and 3: Number of Participants With MAAEs Leading to Discontinuation	From first vaccination on Day 1 up to Day 366 (6 months after booster vaccination on Day 184)	Number of participants with MAAEs leading to discontinuation were reported. MAAEs were 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 were not be considered medically-attended visits. New onset of chronic diseases were collected as part of the MAAEs.
Groups 4, 5 and 6: Number of Participants With MAAEs Leading to Discontinuation	From first vaccination on Day 1 up to Day 240 (6 months after second vaccination on Day 57)	Number of participants with MAAEs leading to discontinuation were reported. MAAEs were 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 were not be considered medically-attended visits. New onset of chronic diseases were collected as part of the MAAEs.
Groups 1, 2, and 3: Number of Participants With Serious Adverse Events (SAEs)	From first vaccination on Day 1 up to Day 366 (6 months after booster vaccination on Day 184)	SAE were defined as 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.
Groups 4, 5 and 6: Number of Participants With Serious Adverse Events (SAEs)	From first vaccination on Day 1 up to Day 240 (6 months after second vaccination on Day 57)	SAE were defined as 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.
Groups 1, 2, 3, 4, 5 and 6: Serological Response to Vaccination Measured by Spike-enzyme-linked Immunosorbent Assay (S-ELISA) at 28 Days Post-dose 1	28 days post-dose 1 on Day 1 (Day 29)	Serological response to vaccination measured by S-ELISA (ELISA Unit/milliliter (EU/mL)) at 28 days post-dose 1 were reported. For Vaccine-specific responses, a participant was defined as a responder if: 1. a baseline sample value of less than or equal to the lower limit of quantification (\<=LLOQ) and a postbaseline sample strictly greater than the LLOQ; or 2. a baseline sample value strictly \>LLOQ and a postbaseline sample value representing an at least 4-fold increase from the baseline sample value, was reported.
Groups 1, 2, and 3: Number of Participants With Adverse Events of Special Interest (AESI) (Including Multisystem Inflammatory Syndrome in Children [MIS-C])	From first vaccination on Day 1 up to Day 366 (6 months after booster vaccination on Day 184)	Number of participants with AESI (including MIS-C) were reported. Thrombotic events (suspected deep vessel venous or arterial thrombotic events); Thrombocytopenia (platelet count below 150,000/μL) and MIS-C (a subject \<21 years with fever, evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement \[cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological\]; \& No alternative diagnoses; \& Positive for ositive for current or recent (SARS-CoV-2) coronavirus disease 2019 \[COVID-19\] infection by Real-time reverse transcriptase-polymerase chain reaction \[RT-PCR\], serology, or antigen test; Or COVID-19 exposure within the 4 weeks prior to the onset of symptoms) were considered AESIs in this study.
Groups 4, 5 and 6: Number of Participants With AESI (Including MIS-C)	From first vaccination on Day 1 up to Day 240 (6 months after second vaccination on Day 57)	Number of participants with AESI (including MIS-C) were reported. Thrombotic events: suspected deep vessel venous or arterial thrombotic events and Thrombocytopenia, defined as platelet count below 150,000/μL and MIS-C were considered as AESIs in this study. MIS-C, defined as: An individual aged \<21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic,or neurological); AND No alternative plausible diagnoses; AND Positive for current or recent SARS-CoV-2 (COVID-19) infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms.
Groups 1, 2, 3, 4, 5 and 6: Serological Response to Vaccination Measured by S-ELISA at 14 Days Post-dose 2	14 days post-dose 2 on Day 57 (Day 71)	Serological response to vaccination measured by S-ELISA (EU/mL) at 14 days post-dose 2 were reported. For Vaccine-specific responses, a participant was defined as a responder if: 1. a baseline sample value of \<=LLOQ and a postbaseline sample strictly greater than the LLOQ; or 2. a baseline sample value strictly \>LLOQ and a postbaseline sample value representing an at least 4-fold increase from the baseline sample value, was reported.

Secondary Outcome Measures

Name	Time	Method
Groups 1, 2 and 3: Number of Participants With Solicited Local AEs for 7 Days Post-booster Vaccination	From first vaccination on Day 1 up to Day 191 (7 days after booster vaccination on Day 184)	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. Solicited AEs were used to assess the reactogenicity of the study vaccine and were pre-defined as local (at the injection site) AEs for which participants were specifically asked and which were noted by participants in their reactogenicity diary for 7 days post each vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, swelling at the vaccination site. Data for this outcome measure was not planned to be collected and analyzed for groups 4, 5 and 6 as pre-specified in the study protocol.
Groups 1, 2 and 3: Number of Participants With MAAEs Until 6 Months Post-booster Vaccination	From first vaccination on Day 1 up to Day 366 (6 months after booster vaccination on Day 184)	MAAEs were 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 were not be considered medically-attended visits. New onset of chronic diseases were collected as part of the MAAEs. Data for this outcome measure was not planned to be collected and analyzed for groups 4, 5 and 6 as pre-specified in the study protocol.
Groups 1, 2 and 3: Number of Participants With Unsolicited AEs for 28 Days Post-booster Vaccination	From first vaccination on Day 1 up to Day 212 (28 days after booster Vaccination on Day 184)	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. Solicited AEs that started within 7 days after vaccination but were ongoing after this 7-day window after each vaccination are also considered unsolicited AEs. Unsolicited AEs were defined as AEs for which the participants were not specifically questioned in the participant's reactogenicity diary. Data for this outcome measure was not planned to be collected and analyzed for groups 4, 5 and 6 as pre-specified in the study protocol.
Groups 1, 2 and 3: Number of Participants With Solicited Systemic AEs for 7 Days Post-booster Vaccination	From first vaccination on Day 1 up to Day 191 (7 days after booster vaccination on Day 184)	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. Solicited AEs were used to assess the reactogenicity of the study vaccine and were predefined as systemic AES for which participants were specifically asked and which were noted by participants in their reactogenicity diary for 7 days post each vaccination. Participants were 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) for the following solicited systemic AEs: fatigue, headache, nausea, myalgia and pyrexia. Data for this outcome measure was not planned to be collected and analyzed for groups 4, 5 and 6 as pre-specified in the study protocol.
Groups 1, 2 and 3: Serological Response to Post-booster Vaccination Measured by Binding (S-ELISA) Antibody Titers	Days 184, 198 and 366	Serological response to post-booster vaccination measured by binding (S-ELISA) antibody titers were reported. For Vaccine-specific responses, a participant was defined as a responder if: 1. a baseline sample value of \<=LLOQ and a postbaseline sample strictly greater than the LLOQ; or 2. a baseline sample value strictly \>LLOQ and a postbaseline sample value representing an at least 4-fold increase from the baseline sample value, was reported. Data for this outcome measure was not planned to be collected and analyzed for groups 4, 5 and 6 as pre-specified in protocol.
Groups 1, 2, 3, 4, 5 and 6: Serological Response to Vaccination Measured by Binding Antibody Titers to Severe Acute Respiratory Syndrome Coronavirus(-2) (SARS-CoV-2) or Individual SARS-CoV-2 S Proteins as Assessed by ELISA	Groups 1-3: Days 1, 29, 57, 71, 184, 198, and 366; Groups 4-6: Days 1, 29, 57, 71 and 240	Serological response to vaccination measured by binding antibody titers to SARS-CoV-2 or individual SARS-CoV-2 S proteins as assessed by ELISA were reported. For Vaccine-specific responses, a participant was defined as a responder if: 1. a baseline sample value of \<=LLOQ and a postbaseline sample strictly greater than the LLOQ; or 2. a baseline sample value strictly \>LLOQ and a postbaseline sample value representing an at least 4-fold increase from the baseline sample value, was reported.
Groups 1, 2, 3, 4, 5 and 6: Serological Response to Vaccination Measured by Neutralizing Antibody Titers to SARS-CoV-2	Groups 1-3: Days 1, 29, 57, 71, 184, 198 and 366; Groups 4-6: Days 1, 29, 57, 71 and 240	Serological response to vaccination measured by neutralizing antibody titers to SARS-CoV-2 (VNA) were reported. For Vaccine-specific responses, a participant was defined as a responder if: 1. a baseline sample value of \<=LLOQ and a postbaseline sample strictly greater than the LLOQ; or 2. a baseline sample value strictly \>LLOQ and a postbaseline sample value representing an at least 4-fold increase from the baseline sample value, was reported. Data were expressed as IC50 units.
Groups 1, 2 and 3: Serological Response to Post-booster Vaccination Measured by Neutralizing (VNA) Antibody Titers	Days 184, 198 and 366	Serological response to post-booster vaccination measured by neutralizing (VNA) antibody titers were reported. For Vaccine-specific responses, a participant was defined as a responder if: 1. a baseline sample value of \<=LLOQ and a postbaseline sample strictly greater than the LLOQ; or 2. a baseline sample value strictly \>LLOQ and a postbaseline sample value representing an at least 4-fold increase from the baseline sample value, was reported. Data were expressed as IC50 units. Data for this outcome measure was not planned to be collected and analyzed for groups 4, 5 and 6 as pre-specified in protocol.

Trial Locations

Locations (18): Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP
🇧🇷
Ribeirão Preto, Brazil
Setshaba Research Centre
🇿🇦
Soshanguve, South Africa
CIPREC
🇦🇷
Buenos Aires, Argentina
Supe Heart And Diabetes Hospital and Research Center
🇮🇳
Nashik, India
JSS Hospital
🇮🇳
Mysore, India
Hospital Universitario Dr Jose Eleuterio Gonzalez
🇲🇽
Monterrey, Mexico
BAPS Pramukhswami Hospital
🇮🇳
Surat, India
CAIMED Investigacion en salud S.A de C.V.
🇲🇽
Ciudad de Mexico, Mexico
Sri ramchandra Medical College & Research Institute
🇮🇳
Chennai, India
Hospital de Ninos de Cordoba
🇦🇷
Córdoba, Argentina
Universidade Federal De Minas Gerais - Hospital das Clínicas
🇧🇷
Belo Horizonte, Brazil
Hospital del Niño Jesús
🇦🇷
San Miguel de Tucumán, Argentina
Santa Casa de Misericordia de Belo Horizonte
🇧🇷
Belo Horizonte, Brazil
CPQuali Pesquisa Clinica LTDA ME
🇧🇷
São Paulo, Brazil
Shandukani Research Centre
🇿🇦
Johannesburg, South Africa
Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital
🇿🇦
Soweto, South Africa
Ndlovu Elandsdoorn Site
🇿🇦
Dennilton, South Africa
University of Witwatersrand - Helen Joseph Hospital - Themba Lethu Hiv Research Centre
🇿🇦
Westdene Johannesburg Gauteng, South Africa