A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19

ModernaTX, Inc.4,328 enrolled

Overview

The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the safety, reactogenicity, and effectiveness of mRNA-1273 vaccine administered as primary series and a booster dose (BD) to an adolescent population. The study will also evaluate the safety and immunogenicity of an mRNA-1273.222 vaccine against the SARS-CoV- 2 omicron variant as a primary series.

This is a Phase 2/3 study, with Part 1A (Blinded Phase), Part 1B (Open-label Observational Phase), Part 1C (Booster Dose \[BD\] Phase), which consists of Part 1C-1 and Part 1C-2, Part 2 (Open-Label), and Part 3 (Open-label). Participants in Part 1A are blinded to their treatment assignment, with participants receiving either 2 active mRNA-1273 vaccine doses or placebo. Part 1B of the study is designed to offer participants whose age group becomes Emergency Use Authorization (EUA) eligible to be unblinded so that participants who received placebo in Part 1A can request 2 doses of open-label mRNA-1273 vaccine. Part 1C-1 of the study will offer participants in Part 1A and Part 1B who are at least 5 months from the last dose, the option to request a homologous BD of mRNA-1273. Part 1C-2 is designed to provide a heterologous BD of mRNA-1273 to eligible participants who completed primary COVID-19 vaccination series with a non-Moderna vaccine under EUA and are at least 3 months from the last dose. Part 2 is an open-label design. Participants will receive 2 doses and may receive a booster dose of mRNA-1273 SARS-CoV-2 vaccine. Part 3 is an open-label design. Participants will receive up to 2 doses of mRNA-1273.222 vaccine. Please access http://TeenCoveStudy.com for additional information, such as Study Overview, Participation, Site Locations along with contact numbers for each location for the study.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Eligibility

Sex: ALLMin age: 12 YearsMax age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: For Part 1A, Part 2 and Part 3: * Participants 12 to \<18 years of age at the time of consent (Screening Visit, Day 0) who, in the opinion of the Investigator, are in good general health based on review of medical history and screening physical examination. * Investigator assessment that the participant, in the case of an emancipated minor, or parent(s)/legally acceptable representative(s) (LAR\[s\]) understand and is willing and physically able to comply with protocol-mandated follow up, including all procedures and provides written informed consent/assent. * Body mass index (BMI) at or above the third percentile according to World Health Organization (WHO) Child Growth Standards at the Screening Visit (Day 0) * Female participants of nonchildbearing potential may be enrolled in the study. Nonchildbearing potential is defined as premenarche or surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy). * Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test at Screening (Day 0), on the day of the first injection (Day 1), on the day of the second injection (Day 29 in Parts 1A and Part 2, and Day 181 in Part 3); has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (Day 1); and has agreed to continue adequate contraception or abstinence through 3 months following the second injection (Day 29 in Part 1A and Part 2, and Day 181 in Part 3). For Part 1B: * Participants must have been previously enrolled in mRNA-1273-P203 study. * Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test on the day of the first injection (Open-Label-Day 1) and on the day of the second injection (Open-Label-Day 29). For Part 1C-1 Homologous Booster Dose: * Participants must have been previously enrolled in the mRNA-1273-P203 study, are actively participating in Part 1A or Part 1B and are least 5 months from the last dose. * Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test on the day of the first injection (BD-Day 1). Part 1C-2 Heterologous Booster Dose: * Male or female, 12 to \< 18 years of age at the time of consent who, in the opinion of the investigator, is in good general health based on review of medical history and screening physical examination AND has completed non-Moderna primary COVID-19 vaccination series under EUA (for example, Pfizer) at least 3 months from consent. Exclusion Criteria: For Part 1A, Part 2, and Part 3: * Has a known history of SARS-CoV-2 infection within 2 weeks prior to administration of investigational product (IP) or known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection of COVID-19 within 2 weeks prior to administration of IP (Part 2 participants only). For Part 3 participants, known history of SARS-CoV-2 infection within 90 days prior to administration of IP or known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection or COVID-19 within 90 days prior to administration of IP. * Travel outside of the United States or home country (Part 2 and Part 3 only) in the 28 days prior to the Screening Visit (Day 0). * Pregnant or breastfeeding * Is acutely ill or febrile 24 hours prior to or at the Screening Visit (Day 0). Fever is defined as a body temperature ≥38.0°Celsius (C)/≥100.4°Farenheit (F). Participants who meet this criterion may have visits rescheduled within the relevant study visit windows. Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator. * Prior administration of an investigational coronavirus (for example, SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome \[MERS-CoV\]) vaccine * Current treatment with investigational agents for prophylaxis against COVID-19 * Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment * Current use of any inhaled substance (for example, tobacco or cannabis smoke, nicotine vapors) * History of chronic smoking (≥1 cigarette a day) within 1 year of the Screening Visit (Day 0) * History of illegal substance use or alcohol abuse within the past 2 years. This exclusion does not apply to historical cannabis use that was formerly illegal in the participant's state but is legal at the time of screening. * History of a diagnosis or condition that, in the judgment of the Investigator, may affect study endpoint assessment or compromise participant safety, specifically: * Congenital or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection * Suspected active hepatitis * Has a bleeding disorder that is considered a contraindication to IM injection or phlebotomy * Dermatologic conditions that could affect local solicited AR assessments * History of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine * Diagnosis of malignancy within the previous 10 years (excluding nonmelanoma skin cancer) * Febrile seizures * Receipt of: * Any licensed vaccine within 28 days before the first dose of IP or plans for receipt of any licensed vaccine within 28 days before and/or after each dose of IP. * Systemic immunosuppressants or immune-modifying drugs for \>14 days in total within 6 months prior to the day of enrollment (for corticosteroids, ≥20 mg/day prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to the day of enrollment. Participants may have visits rescheduled for enrollment if they no longer meet this criterion within the Screening Visit window. Inhaled, nasal, and topical steroids are allowed. * Intravenous blood products (red cells, platelets, immunoglobulins) within 3 months prior to enrollment * Has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit (Day 0) or plans to donate blood products during the study * Participated in an interventional clinical study within 28 days prior to the Screening Visit (Day 0) or plans to do so while participating in this study * Is an immediate family member or has a household contact who is an employee of the research center or otherwise involved with the conduct of the study For Part 1C-1 and Part 1C-2: * Pregnant or breastfeeding. * Is acutely ill or febrile 24 hours prior to or at the Screening Visit (Day 0). Fever is defined as a body temperature ≥ 38.0°C/≥ 100.4°F. Participants who meet this criterion may have visits rescheduled within the relevant study visit windows. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator. * Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the investigator's judgment. * History of a diagnosis or condition (after enrolment in Part 1A) that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety: * Suspected active hepatitis * Has a bleeding disorder that is considered a contraindication to IM injection or phlebotomy * Dermatologic conditions that could affect local solicited AR assessments * History of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine * Diagnosis of malignancy (excluding nonmelanoma skin cancer) * Receipt of: • Any authorized or licensed vaccine within 28 days before the first dose of IP or plans for receipt of any licensed vaccine through 28 days following the last dose of IP or any seasonal influenza vaccine within 14 days before the first dose of IP or plans for receipt of any seasonal influenza vaccine 14 days following the last dose of IP. * Participated in an interventional clinical study, other than mRNA-1273-P203 study, within 28 days prior to the Screening Visit (Day 0 \[for Part 1C-1\], BD-Day 0 \[for Part 1C-2\]) or plans to do so while participating in this study. Part 1C-2 Heterologous Booster Dose: * Has a known history of SARS-CoV-2 infection within 2 weeks prior to administration of IP or known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection or COVID 19 within 2 weeks prior to administration of IP.

Outcomes

Primary Outcomes

Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)

Solicited ARs (local and systemic) were collected in an electronic diary (eDiary). Local ARs included injection site pain, injection site erythema (redness), injection site swelling/induration (hardness), and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs included fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Solicited ARs considered causally related to injection were graded 1-4 (per Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials); lower score indicated lower severity, and higher score indicated greater severity. Investigator reviewed if the solicited AR was recorded as an adverse event (AE) as detailed in the AE section. A Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the AE section.

Time frame: 7 days post-vaccination

Number of Participants With Unsolicited AEs

An unsolicited AE was any AE reported by the participant that was not specified as a solicited AR in the protocol or was specified as a solicited AR but started outside the protocol-defined period for reporting solicited ARs (onset after Day 7 of dosing). An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result or other safety assessment, including one that worsened from baseline and was considered clinically significant by the Investigator was recorded as an AE. Non-serious SARs persisting beyond 7 days, leading to discontinuation, or medically attended were classified as AEs in Part 1/2 but not in Part 3. COVID-19/SARS-CoV-2 infections were AEs in Part1/2 but were considered clinical events for efficacy in Part 3 and not AEs. A Summary of SAEs and nonserious AEs ("Other"), regardless of causality, is located in the AE section.

Time frame: Up to 28 days post-vaccination

Part 1A Geometric Mean Value of Serum Pseudovirus Neutralizing Antibody (nAb) ID50 Titers From Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Pseudovirus nAb ID50 titers were measured using pseudovirus neutralization assay (PsVNA) assay. Antibody values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5\*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ if actual values were not available (LLOQ: 18.5 arbitrary units (AU)/milliliter (mL), ULOQ: 45118 AU/mL). Antibody levels were analyzed using an analysis of covariance (ANCOVA) model with the group variable (adolescents in P203 and young adults in P301) as fixed effect. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria were used for comparison assessments of immune response.

Time frame: Day 57 Study P203/Day 57 Study P301

Part 1A Seroresponse Rate (SRR) for Serum Pseudovirus nAb ID50 in Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Percentage of participants with seroresponse for pseudovirus nAb ID50 measured using PsVNA assay are reported. Seroresponse was defined as a change from below the LLOQ to equal above 4\*LLOQ, or at least a 4-fold rise if baseline is equal to or above the LLOQ (LLOQ: 18.5 AU/mL), ULOQ: 45118 AU/mL). PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria were used for comparison assessments of immune response.

Time frame: Day 57 Study P203/Day 57 Study P301

Part 1C-1 Geometric Mean Concentration (GMC) of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Pseudovirus nAb were measured using PsVNA assay. Antibody values reported as below the LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available (LLOQ: 10, ULOQ: 281600). PPIS P301: randomly selected participants from study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison assessments of immune response.

Time frame: BD Day 29 Study P203/Day 57 Study P301

Part 1C-1 SRR of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Percentage of participants with seroresponse for pseudovirus nAb measured using PsVNA assay are reported. Seroresponse relative to pre-Dose 1 (baseline) at a participant level was defined as a change from below the LLOQ to equal or above 4 \* LLOQ, or at least a 4-fold-rise if baseline was equal to or above LLOQ (LLOQ: 10 AU/mL, ULOQ: 281600 AU/mL). PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison assessments of immune response.

Time frame: BD Day 29 Study P203/Day 57 Study P301

Part 3 GMC of nAb Post Dose 1 mRNA 1273.222 Against Omicron BA.4/BA.5 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Antibody values reported as below the LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available (LLOQ: 103 AU/mL, ULOQ: 28571 AU/mL). ANCOVA model with the group variable (adolescents in P203 and young adults in P301) as fixed effect. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison of immune response.

Time frame: Day 29 Study P203/Day 57 Study P301

Part 1C-2 GMC of Post-booster Pseudovirus nAb Against Ancestral Strain at BD Day 29

Time frame: BD Day 29

Part 2 GMC of the Pseudovirus nAb Against Ancestral Strain at Day 57

Time frame: Day 57

Part 3 GMC of nAb Post Dose 1 mRNA 1273.222 Against SARS-CoV-2 Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Antibody values reported as below the LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available (LLOQ: 10 AU/mL, ULOQ: 111433 AU/mL). ANCOVA model with the group variable (adolescents in P203 and young adults in P301) as fixed effect. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison of immune response.

Time frame: Day 29 Study P203/Day 57 Study P301

Part 2 SRR of Pseudovirus nAb Against Ancestral Strain

Time frame: Day 57

Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation

SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. AESIs were identified based upon medical concepts that may be related to COVID-19 or were of interest in COVID-19 vaccine safety surveillance. MAAE was an AE that led to an unscheduled visit to a healthcare practitioner, included visits to a study site for unscheduled assessments (for example, abnormal laboratory follow-up, and visits to healthcare practitioners external to the study site \[for example, urgent care, primary care physician\]). Non-serious SARs persisting beyond 7 days, leading to discontinuation, or medically attended were defined as AEs in Part 1/2 but not in Part 3. COVID-19/SARS-CoV-2 infections were AEs in Part 1/2 but were considered clinical events for efficacy in Part 3 and not AEs.

Time frame: Day 1 up to Day 751

Secondary Outcomes

Part 1A Number of Participants With a SARS-CoV-2 Infection (Symptomatic or Asymptomatic)

SARS-CoV-2 infection was defined in participants with negative SARS-CoV-2 status at baseline: bAb level against SARS-CoV-2 nucleocapsid protein negative at Day 1, that became positive postbaseline; or positive postbaseline.

Time frame: Day 43 (14 days after second injection) up to a median follow up of 2.5 months after second injection

Part 1A Number of Participants With Asymptomatic SARS-CoV-2 Infection

Asymptomatic SARS-CoV-2 infection was defined as absence of symptoms and a positive RT-PCR or serology test (bAb levels against SARS-CoV-2 nucleocapsid protein) post dosing in participants who did not have an infection at baseline or pre-Dose 1.

Time frame: Day 43 (14 days after second injection) up to a median follow up of 2.5 months after second injection

Part 1A Number of Participants With a First Occurrence of Symptomatic COVID-19

COVID-19 was defined as symptomatic disease based on the following criteria: participants experienced at least 2 of the following systemic symptoms: fever (≥ 38ºC/≥ 100.4ºF), chills, myalgia, headache, sore throat, new olfactory and taste disorder(s); or experienced at least 1 of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia; and had at least 1 nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2.

Time frame: Day 43 (14 days after second injection) up to 2.5 months after second injection

Part 1A Number of Participants With Secondary Case Definition of COVID-19 (Center for Disease Control and Prevention [CDC] Case Definition)

Secondary case definition of COVID-19 was defined by the following criteria: 1 systemic or respiratory symptoms: fever (temperature \> 38ºC/≥ 100.4ºF), or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches, or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, or vomiting or diarrhea, and at least one positive test for SARS-CoV-2.

Time frame: Day 43 (14 days after second injection) up to a median follow up of 2.5 months after second injection

A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19

Overview

Conditions

Interventions

Eligibility

Locations (53)

Outcomes

Primary Outcomes

Secondary Outcomes