Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 COVID-19 Vaccine in Adults Aged 18 Years and Older

Sponsor

ModernaTX, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04405076

Collaborator

Biomedical Advanced Research and Development Authority (U.S. Fed)

660

Enrollment

Locations

Arms

16.9

Actual Duration (Months)

82.5

Patients Per Site

4.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical study will assess the safety, reactogenicity, and immunogenicity of 2 dose levels of mRNA-1273 Severe Acute Respiratory Syndrome coronavirus (SARS-COV-2) vaccine in adults 18 years of age or older.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2	Biological: Biological: mRNA-1273 Biological: Placebo Biological: mRNA-1273.351	Phase 2

Detailed Description

This is a 3-part Phase 2a study, with Part A (Blinded Phase), Part B (Open-label Interventional Phase), and Part C (Rollover Proof of Concept).

Participants in Part A are blinded to their treatment assignment, with participants receiving either 2 active mRNA-1273 vaccine doses or placebo. Part B of the study is designed to offer participants to be unblinded so that participants who received placebo in Part A can request 2 doses of open-label mRNA-1273 vaccine. Additionally, participants who originally received 1 or 2 doses of mRNA-1273 (50 microgram [μg] or 100 μg vaccine) during Part A, will have the opportunity to request to receive a single booster dose of mRNA-1273.

Part C will be a proof-of-concept rollover study to evaluate a vaccine to treat mutations of SARS-CoV2, such as the S-protein of the B.1.351 variant. Part C will include approximately 60 participants, who are currently enrolled in Moderna's Phase 3 mRNA-1273-P301 study (NCT04470427), have already been unblinded, and have previously received 2 doses of mRNA-1273 at least 6 months earlier. At enrollment into Part C of this study, their participation in mRNA-1273-P301 study will be terminated. Part C will evaluate the safety and immunogenicity of 2 dose levels (20 µg and 50 µg) of mRNA-1273.351 and mRNA-1273/mRNA-1273.351 mixture (50 µg total), given as a single booster dose.

Study Design

Study Type:

Interventional

Actual Enrollment :

660 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Part A is observer-blind. During Part B participants may request to be unblinded by scheduling a Participant Decision clinic visit. Part C is open-label.

Primary Purpose:

Prevention

Official Title:

A Phase 2a, Randomized, Observer-Blind, Placebo Controlled, Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 SARS-COV-2 Vaccine in Adults Aged 18 Years and Older

Actual Study Start Date :

May 29, 2020

Actual Primary Completion Date :

Oct 26, 2021

Actual Study Completion Date :

Oct 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mRNA-1273: Dose 50 microgram (ug) - Participants Aged 18-54 years Part A: Participants aged 18-54 years will receive 1 intramuscular (IM) injection of 50 ug mRNA-1273 on Day 1 and on Day 29. Part B: Participants aged 18-54 years who choose to be unblinded and received 50 ug mRNA-1273 during Part A, will receive 1 IM injection of mRNA-1273 (booster dose) on Day 1.	Biological: Biological: mRNA-1273 Sterile liquid for injection
Experimental: mRNA-1273: Dose 50 ug - Participants Aged 55+ years Part A: Participants aged 55+ years will receive 1 IM injection of 50 ug mRNA-1273 on Day 1 and on Day 29. Part B: Participants aged 55+ years who choose to be unblinded and received 50 ug mRNA-1273 during Part A, will receive 1 IM injection of mRNA-1273 (booster dose) on Day 1.	Biological: Biological: mRNA-1273 Sterile liquid for injection
Experimental: mRNA-1273: Dose 100 ug - Participants Aged 18-54 years Part A: Participants aged 18-54 years will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and on Day 29. Part B: Participants aged 18-54 years who choose to be unblinded and received 100 ug mRNA-1273 during Part A, will receive 1 IM injection of mRNA-1273 (booster dose) on Day 1.	Biological: Biological: mRNA-1273 Sterile liquid for injection
Experimental: mRNA-1273: Dose 100 ug - Participants Aged 55+ years Part A: Participants aged 55+ years will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and on Day 29. Part B: Participants aged 55+ years who choose to be unblinded and received 100 ug mRNA-1273 during Part A, will receive 1 IM injection of mRNA-1273 (booster dose) on Day 1.	Biological: Biological: mRNA-1273 Sterile liquid for injection
Placebo Comparator: Placebo (Part A) and mRNA-1273 100 ug (Part B) - Participants Aged 18-54 years Part A: Participants aged 18-54 years will receive 1 IM injection of mRNA-1273-matching placebo on Day 1 and on Day 29. Part B: Participants aged 18-54 who choose to be unblinded and received mRNA-1273-matching placebo during Part A, will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and Day 29.	Biological: Biological: mRNA-1273 Sterile liquid for injection Biological: Placebo 0.9% sodium chloride (normal saline) injection
Placebo Comparator: Placebo (Part A) and mRNA-1273 100 ug (Part B) - Participants Aged 55+ years Part A: Participants aged 55+ years will receive 1 IM injection of mRNA-1273-matching placebo on Day 1 and on Day 29. Part B: Participants aged 55+ years who choose to be unblinded and received mRNA-1273-matching placebo during Part A, will receive 1 IM injection of 100 ug mRNA-1273 on Day 1 and Day 29.	Biological: Biological: mRNA-1273 Sterile liquid for injection Biological: Placebo 0.9% sodium chloride (normal saline) injection
Experimental: mRNA 1273.351 20 ug (Part C) Part C: Participants will receive 1 IM booster dose of 20 ug of mRNA 1273.351 on Day 1.	Biological: mRNA-1273.351 Sterile liquid for injection
Experimental: mRNA 1273.351 50 ug (Part C) Part C: Participants will receive 1 IM booster dose of 50 ug of mRNA 1273.351 on Day 1.	Biological: mRNA-1273.351 Sterile liquid for injection
Experimental: mRNA-1273/mRNA-1273.351 mixture (Part C) Part C: Participants will receive 1 IM booster dose of 50 ug of mRNA-1273/mRNA-1273.351 mixture on Day 1.	Biological: Biological: mRNA-1273 Sterile liquid for injection Biological: mRNA-1273.351 Sterile liquid for injection

Outcome Measures

Primary Outcome Measures

Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [7 days post-vaccination]
Number of Participants with Unsolicited Adverse Events (AEs) [28 days post-vaccination]
Number of Participants with Medically-Attended Adverse Events (MAAEs) [Up to Month 15]
Number of Participants with Serious Adverse Events (SAEs) [Up to Month 15]
Change from Baseline in the Measure of Clinical Safety Laboratory Values in Cohort 2 [Part A: Baseline, 1 month after last vaccination]
Number of Participants with Abnormalities in Blood Pressure, Temperature, HR, or Respiratory Rate [Up to Month 15]
Number of Participants with Abnormalities in Physical Examinations [Up to Month 15]
Level of SARS-CoV-2-Specific Binding Antibody (bAb) as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) [Day 1 through 6 months after last vaccination]

Secondary Outcome Measures

Titer of SARS-CoV-2-Specific Neutralizing Antibody (nAb) [Day 1 through 6 months after last vaccination]
Seroconversion as Measured by an Increase of SARS-CoV-2-Specific Neutralizing Antibody (nAb) Titer [Day 1 through 6 months after last vaccination]
Seroconversion as measured by an increase of SARS-CoV-2-nAb titer either from below the limit of detection (LOD) or lower limit of quantification (LLOQ) to equal to or above LOD or LLOQ, or a 4-times higher titer in participants with pre-existing nAb titers.
Level of SARS CoV-2-Specific Serum Binding Antibody [Day 1 through 6 months after last vaccination]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Key Inclusion Criteria:

Each participant must meet all of the following criteria during the screening period and at

Day 1, unless noted otherwise, to be enrolled in this study:

Male or female, 18 years of age or older at the time of consent (Screening Visit, Day 0). For Part B, participants must have been previously enrolled in the mRNA-1273 P201 study.
Understands and agrees to comply with the study procedures and provides written informed consent.
According to the assessment of the investigator, is in good general health and can comply with study procedures.
Female participants of nonchildbearing potential may be enrolled in the study. Nonchildbearing potential is defined as surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy) or postmenopausal (defined as amenorrhea for ≥12 consecutive months prior to Screening (Day 0) without an alternative medical cause). A follicle-stimulating hormone (FSH) level may be measured at the discretion of the investigator to confirm postmenopausal status.
Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:

Has a negative pregnancy test at Screening (Day 0) and on the day of the first injection (Day 1).
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).
Has agreed to continue adequate contraception through 3 months following the second injection (Day 29).
Is not currently breastfeeding.

Adequate female contraception is defined as consistent and correct use of a Food and Drug Administration (FDA) approved contraceptive method in accordance with the product label. For example:

Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction with spermicide
Intrauterine device
Prescription hormonal contraceptive taken or administered via oral (pill), transdermal (patch), subdermal, or IM route
Sterilization of a female participant's monogamous male partner prior to entry into the study Note: periodic abstinence (for example, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Male participants engaging in activity that could result in pregnancy of sexual partners must agree to practice adequate contraception from the time of the first injection and through 3 months after the last injection.

Adequate contraception for male participants is defined as:

Monogamous relationship with a female partner using an intrauterine device or hormonal contraception (described above)
Use of barrier methods and spermicide
History of surgical sterilization
Male participants with partners who have become pregnant prior to Screening are eligible to participate in the study.

Additional Key Inclusion Criteria for Part C

Participants must have been previously enrolled in the mRNA-1273-P301 study and must have received 2 doses of mRNA-1273 in Part A, has been unblinded and aware of their actual treatment in Study mRNA-1273-P301, must have been compliant in Study mRNA-1273-P301 (was not withdrawn or discontinued early), and has been at least 6 months since their second dose in Study mRNA-1273-P301 prior to enrollment in this part.

Key Exclusion Criteria:

Participants meeting any of the following criteria at the Screening Visit (Day 0) or at Day 1, unless noted otherwise, will be excluded from the study:

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/100.4°Fahrenheit. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
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.
Is a healthcare worker or a member of an emergency response team.
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.
Known history of hypertension, or systolic blood pressure >150 millimeter of mercury (mmHg) in participants in Cohort 1 (≥18 to <55 years old) or systolic blood pressure

160 mmHg in participants in Cohort 2 (≥55 years old) at the Screening Visit (Day 0).

Known history of hypotension or systolic blood pressure <85 mmHg at the Screening Visit (Day 0).
Diabetes mellitus
Diagnosis of chronic pulmonary disease (for example, chronic obstructive pulmonary disease, asthma)
Chronic cardiovascular disease
Resides in a nursing home
Grade 1 or higher toxicity on clinical safety laboratory testing at the Screening Visit (Day 0)
Current or previous diagnosis of immunocompromising condition, immune-mediated disease, or other immunosuppressive condition.
Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to the Screening Visit (Day 0) (for corticosteroids ≥20 milligrams (mg)/day of prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to the Screening Visit (Day 0).
Anticipating the need for immunosuppressive treatment at any time during participation in the study.
Positive serology for hepatitis B virus surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) type 1 or 2 antibodies identified at the Screening Visit (Day 0).
History of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine.
Bleeding disorder considered a contraindication to IM injection or phlebotomy.
Diagnosis of malignancy within previous 10 years (excluding non-melanoma skin cancer).
Has received or plans to receive a licensed vaccine ≤28 days prior to the first injection (Day 1) or plans to receive a licensed vaccine within 28 days before or after any study injection. Licensed influenza vaccines may be received more than 14 days before or after any study injection.
Receipt of systemic immunoglobulins or blood products within 3 months prior to the Screening Visit (Day 0) or plans for receipt during the study.
Has donated ≥450 mL of blood products within 28 days prior to the Screening Visit (Day

or plans to donate blood products during the study.

Participated in an interventional clinical study (other than mRNA-1273 P301) 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 household member of study personnel

Additional Key Exclusion Criteria for Part C

Is SARS-CoV-2 positive by Reverse transcription polymerase chain reaction (RT-PCR) (central or local testing) at baseline or at any time during the mRNA-1273-P301 study regardless of the presence or absence of symptoms consistent with COVID-19.
Had any SAE in the mRNA-1273-P301 study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Meridian Clinical Research	Savannah	Georgia	United States	31406
2	Alliance for Multispecialty Research	Newton	Kansas	United States	67114
3	Alliance for Multispecialty Research	Kansas City	Missouri	United States	64114
4	Meridian Clinical Research	Norfolk	Nebraska	United States	68701
5	Trial Management Associates	Wilmington	North Carolina	United States	28403
6	Meridian Clinical Research	Dakota Dunes	South Dakota	United States	57049
7	Benchmark Research	Austin	Texas	United States	78705
8	Benchmark Research	San Angelo	Texas	United States	76904