| Protocol No: | ECCT/23/03/03 | Date of Protocol: | 11-10-2022 |
| Study Title: | A Phase 2/3, Randomized, Observer-Blind, Placebo‑Controlled Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA‑1273 SARS‑CoV‑2 Vaccine in Healthy Adolescents 12 to <18 Years of Age |
| Study Objectives: | Primary Objectives - To evaluate the safety and reactogenicity of 100 mg mRNA‑1273 vaccine administered in 2 doses 28 days apart - To infer efficacy of mRNA-1273 (100 µg, 2 doses 28 days apart), serum Ab responses obtained 28 days after the second injection of mRNA‑1273 (Day 57) will be either: * Evaluated against an accepted Ab threshold of protection against COVID‑19 (if established in Study P301) * Compared in primary vaccine response as measured by GM values of serum Ab and SRR in Study P203 with those obtained from young adult recipients (18 to 25 years of age) of mRNA‑1273 in the clinical endpoint efficacy trial (Study P301) Secondary Objectives - To evaluate the persistence of the immune response of mRNA‑1273 vaccine (100 mg) administered in 2 doses 28 days apart, as assessed by the level of SARS‑CoV‑2 S2P‑specific bAb through 1 year after Dose 2 - To evaluate the persistence of the immune response of mRNA‑1273 vaccine (100 mg) administered in 2 doses 28 days apart, as assessed by the level of nAb through 1 year after Dose 2 - To evaluate the effect of mRNA‑1273 on the incidence of SARS‑CoV-2 infection compared with the incidence among placebo recipients To evaluate the incidence of asymptomatic SARS-CoV-2 infection after vaccination with mRNA-1273 or placebo - To evaluate the incidence of COVID‑19 after vaccination with mRNA‑1273 or placebo. COVID‑19 is defined as clinical symptoms consistent with SARS‑CoV‑2 infection AND positive RT‑PCR for SARS‑CoV-2 Exploratory Objectives - To evaluate the genetic and/or phenotypic relationships of isolated SARS‑CoV‑2 strains to the vaccine sequence - To describe the ratio or profile of specific bAb relative to nAb in serum - To characterize the clinical profile and immune responses of participants with COVID‑19 or with SARS‑CoV‑2 infection - To evaluate the incidence of asymptomatic SARS-CoV-2 infection after vaccination with mRNA-1273 or placebo in participants with serologic evidence of infection at baseline |
| Laymans Summary: | Part 1B, the Open-label Observational Phase of this study, is designed to offer participants who received placebo in Part 1A of this study and who meet the EUA eligibility criteria an option to receive mRNA-1273 in an open-label fashion (Figure 3). Participants who received mRNA-1273 (100 μg) in Part 1A of this study will proceed to Part 1B after they are unblinded and will continue to follow the Part 1A SoA (Table 10). Part 1C-1, the Homologous Booster Dose Phase, is designed to offer participants in Part 1A and Part 1B, and who are at least 5 months from the last dose, the option to request a BD of 50 μg mRNA-1273. Part 1C-2, the Heterologous Booster Phase, is designed to provide participants who completed non Moderna primary COVID-19 vaccination series under EUA (ie, Pfizer) a 50 μg BD of mRNA-1273 at least 3 months from the last dose. Part 2 is an open-label design. The study will evaluate the safety, reactogenicity, and effectiveness of a 50 μg primary series of mRNA-1273 SARS-CoV-2 vaccine in 2 doses 4 weeks apart, in healthy adolescents 12 to < 18 years of age. The enrolment for this study is open only for Part 3. The goal of the Part 3 of this study is to seek an indication for use of bivalent mRNA-1273.222 (100 μg IM, given as 2 injections, 6 months apart) in the 12 to < 18 years age group, COVID-19 vaccine naïve participants. Addition in a part 3 of the study is testing the safety and effectiveness of a bivalent mRNA vaccine against original strain and Omicron in the young adolescent population. This study in adolescents will monitor all participants for a total of 6 months following the second dose of vaccine. Safety assessments will include solicited ARs (7 days after each injection), unsolicited AEs (28 days after each injection), MAAEs, SAEs, and AESIs (including MIS-C) throughout the study period. Blood samples will be collected from all participants at baseline (Day 1), Day 29 (28 days after Dose 1), Day 85 (3 months after Dose 1), Day 181 (Dose 2), Day 209 (1 month after Dose 2), and Day 361 (6 months after Dose 2) for measurement of SARS-CoV-2 specific bAb and nAb responses. Blood samples will also be tested for the development of Ab directed against nonvaccine antigen, which will signify infection with SARS-CoV-2. Blood samples will be collected 3 days after Dose 1 and 3 days after Dose 2 (Day 184), for future biomarker analysis (ie, inflammatory and/or cardiac biomarkers). |
| Abstract of Study: | This is a three-part, Phase 2/3 study: Part 1A, Part 1B, and Part 1C. Participants in Part 1A, the Blinded Phase, are blinded to their treatment assignment. Part 1B, the Open-label Observational Phase of this study, is designed to offer participants who received placebo in Part 1A of this study and who meet the EUA eligibility criteria an option to receive mRNA‑1273 in an open-label fashion (Figure 3). Participants who received mRNA‑1273 (100 µg) in Part 1A of this study will proceed to Part 1B after they are unblinded and will continue to follow the Part 1A SoA (Table 10). Part 1C-1, the Homologous Booster Dose Phase, is designed to offer participants in Part 1A and Part 1B, and who are at least 5 months from the last dose, the option to request a BD of 50 µg mRNA-1273. Part 1C-2, the Heterologous Booster Phase, is designed to provide participants who completed non Moderna primary COVID-19 vaccination series under EUA (ie, Pfizer) a 50 µg BD of mRNA-1273 at least 3 months from the last dose. Participants who received mRNA-1273 in Part 1A will be in the study approximately 25 months if a BD is received in Part 1C-1, which includes 1 month for screening (Day ˗28 to Day 1), up to 12 months for dosing (on Day 1, Day 29, and Day 209 for BD), and 12 months for follow-up. Participants who received placebo in Part 1A will be in the study for approximately 25 months total if a BD is received in Part 1C-1, which includes approximately 9 months in Part 1A and approximately 4 months of follow‑up following their second dose of mRNA-1273 in Part 1B before entering Part 1C-1 or before BD is received; or approximately 12 months of follow-up. Participants that decline unblinding or decline to receive a BD will be in the study approximately 14 months total, which includes 1 month for screening (Day -28 to Day 1), 1 month for dosing (on Day 1 and Day 29), and 12 months for follow-up. Participants in Part 1C-2 will be in the study for approximately 12 months total, which includes 7 days for screening (Day -7 to Day 1), 1 day of dosing (BD-Day 1), and 12 months of follow-up. This study will be conducted in compliance with the protocol, GCP, and all applicable regulatory requirements.
The blinded phase of this study is a randomized, observer-blind, placebo-controlled study intended to infer the effectiveness of mRNA-1273 in an adolescent population aged 12 to < 18 years. The study includes 2 arms: (i) 100 µg of mRNA-1273, and (ii) placebo. Approximately, 3000 participants between 12 to < 18 years of age will be randomly assigned in a 2:1 ratio to receive mRNA-1273 (n=2000) or placebo (n=1000). The schematic of study arms and major study events for Part 1A is illustrated in Figure 2and the SoA for Part 1A is located in Table 10. The goal of the study is to seek an indication for use of mRNA‑1273 (100 µg IM, given as 2 injections, 28 days apart) in the 12 to < 18 years age group. The basis for demonstrating vaccine effectiveness is proposed to be met by serum Ab response measured in this adolescent age group. The approach to inferring vaccine effectiveness will depend on whether an accepted serum Ab threshold conferring protection against COVID-19 has been established. If an Ab threshold of protection has been established, effectiveness will be inferred based on the proportion of adolescent study participants with serum Ab levels (on Day 57) that meet or exceed the Ab threshold. If an Ab threshold of protection has not been established, effectiveness will be inferred by demonstrating noninferiority of both (i) the GM value of serum nAb and (ii) the SRR from adolescent participants compared with those from young adults (18 to 25 years of age) enrolled in the ongoing clinical endpoint efficacy trial (Study P301). The statistical parameters to infer effectiveness are described in Section 2. This study in adolescents will monitor all participants for a total of 12 months following the second dose of vaccine or placebo. Safety assessments will include solicited ARs (7 days after each injection), unsolicited AEs (28 days after each injection), MAAEs, SAEs, and AESIs (including MIS‑C) throughout the study period.
Blood samples will be collected from all participants at baseline (Day 1), Day 57 (28 days after Dose 2), Day 209 (6 months after Dose 2), and Day 394 for measurement of
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