Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines

COVID-19 Clinical Trial

Official title:

A Phase 1/2 Study of Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04889209
• Other study ID #: 21-0012
• Secondary ID: 5UM1AI148684-05
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 28, 2021
• Est. completion date: June 16, 2023

Study information

• Verified date: June 13, 2023
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase 1/2, open-label clinical trial in individuals, 18 years of age and older, who are in good health, have no known history of Coronavirus Disease 2019 (COVID-19) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and meet all other eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of a delayed (>/=12 weeks) vaccine boost on a range of Emergency Use Authorization (EUA)-dosed COVID-19 vaccines (mRNA-1273, and mRNA-1273.211 manufactured by ModernaTX, Inc.; BNT162b2 manufactured by Pfizer/BioNTech; or Ad26.COV2.S manufactured by Janssen Pharmaceuticals/Johnson & Johnson). This is an adaptive design and may add arms (and increase sample size) as vaccines are awarded EUA and/or variant lineage spike vaccines are manufactured or become available. Enrollment will occur at up to twelve domestic clinical research sites.

This study includes two cohorts. Cohort 1 will include approximately 880 individuals (50 subjects/group; Groups 1E-11E) greater than 18 years of age and older, stratified into two age strata (18-55 years and >/=56 years) who previously received COVID-19 vaccine at Emergency Use Authorization dosing (EUA) (two vaccinations of mRNA-1273 at the 100 mcg dose, two vaccinations of BNT162b2 at the 30 mcg dose, or one vaccination of Ad26.COV2.S at the 5x10^10 vp dose). Groups 15E-17E will enroll 60 subjects, split (approximately evenly) between age strata as able. Those subjects will be offered enrollment into this study >/=12 weeks after they received the last dose of their EUA vaccine. Subjects will receive a single open-label intramuscular (IM) injection of the designated delayed booster vaccine and will be followed through 12 months after vaccination: 1) Group 1E - previously EUA-dosed vaccination with Janssen - Ad26.COV.2.S at 5x10^10 vp followed by a 100-mcg dose of mRNA-1273, Group 4E - previously EUA-dosed vaccination with Janssen - Ad26.COV.2.S at 5x10^10 vp followed by a 5x10^10 vp dose of Ad26.COV2.S, Group 7E - previously EUA-dosed vaccination with Janssen - Ad26.COV.2.S 5x10^10 vp followed by a 30-mcg dose of BNT162b2, Group 10E - previously EUA-dosed vaccination with Janssen - Ad26.COV2-S 5x10^10 vp followed by a 100-mcg dose of mRNA-1273.211; Group 12E - previously EUA-dosed vaccination with Janssen - Ad26.COV2-S 5x10^10 vp followed by a 50-mcg dose of mRNA-1273; Group 15E - previously EUA-dosed vaccination with Janssen (two doses for Group 15E) - Ad26.COV2.S at 5x1010 vp followed by a dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV-2 rS vaccine with 50 mcg Matrix-M); 2) Group 2E

• previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed by a 100-mcg dose of mRNA-1273, Group 5E - previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed by a 5x10^10 vp dose of Ad26.COV2.S, Group 8E - previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed by a 30-mcg dose of BNT162b2, Group 13E - previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed by a 50-mcg dose of mRNA-1273; Group 16E - previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed by a dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV2 rS vaccine with 50 mcg Matrix-M); 3) Group 3E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 100-mcg dose of mRNA-1273. Group 6E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 5x10^10 vp dose of Ad26.COV2.S, Group 9E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 30-mcg dose of BNT162b2, Group 11E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 100-mcg dose of mRNA-1273.211. Group 14E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 50-mcg dose of mRNA-1273, Group 17E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV2 rS vaccine with 50 mcg Matrix-M).

A telephone visit will occur one week after each primary EUA vaccination and one week after the booster dose. In person follow-up visits will occur on 14 days following completion of EUA vaccinations and on days 14, and 28 days after the booster dose, as well as 3, 6, and 12 months post the booster vaccination. Additional pools of subjects can be included if needed as additional COVID-19 vaccines are awarded EUA.

The primary objectives of this study are 1) to evaluate the safety and reactogenicity of delayed heterologous or homologous vaccine doses after EUA dosed vaccines, and 2) to evaluate the breadth of the humoral immune responses of heterologous and homologous delayed boost regimens following EUA dosing.

Description:

A phase 1/2, open-label clinical trial in individuals, 18 years of age and older, who are in good health, have no known history of Coronavirus Disease 2019 (COVID-19) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and meet all other eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of a delayed (>/=12 weeks) vaccine boost on a range of Emergency Use Authorization (EUA)-dosed COVID-19 vaccines (mRNA-1273, and mRNA-1273.211 manufactured by ModernaTX, Inc.; BNT162b2 manufactured by Pfizer/BioNTech; or Ad26.COV2.S manufactured by Janssen Pharmaceuticals/Johnson & Johnson). This is an adaptive design and may add arms (and increase sample size) as vaccines are awarded EUA and/or variant lineage spike vaccines are manufactured or become available. Enrollment will occur at up to twelve domestic clinical research sites.

This study includes two cohorts. Cohort 1 will include approximately 880 individuals (50 subjects/group; Groups 1E-14E, and 60 subjects/group; Groups 15E-17E) greater than 18 years of age and older, stratified into two age strata (18-55 years and >/=56 years) who previously received COVID-19 vaccine at Emergency Use Authorization dosing (EUA) (two vaccinations of mRNA-1273 at the 100 mcg dose, two vaccinations of BNT162b2 at the 30 mcg dose, or one vaccination of Ad26.COV2.S at the 5x10^10 vp dose). Groups 15E-17E will enroll 60 subjects, split (approximately evenly) between age strata as able. Those subjects will be offered enrollment into this study >/=12 weeks after they received the last dose of their EUA vaccine. Subjects will receive a single open-label intramuscular (IM) injection of the designated delayed booster vaccine and will be followed through 12 months after vaccination: 1) Group 1E - previously EUA-dosed vaccination with Janssen - Ad26.COV.2.S at 5x10^10 vp followed by a 100-mcg dose of mRNA-1273, Group 4E - previously EUA-dosed vaccination with Janssen - Ad26.COV.2.S at 5x10^10 vp followed by a 5x10^10 vp dose of Ad26.COV2.S, Group 7E - previously EUA-dosed vaccination with Janssen - Ad26.COV.2.S 5x10^10 vp followed by a 30-mcg dose of BNT162b2, Group 10E - previously EUA-dosed vaccination with Janssen - Ad26.COV2-S 5x10^10 vp followed by a 100-mcg dose of mRNA-1273.211; Group 12E - previously EUA-dosed vaccination with Janssen - Ad26.COV2-S 5x10^10 vp followed by a 50-mcg dose of mRNA-1273; Group 15E - previously EUA-dosed vaccination with Janssen (two doses for Group 15E) - Ad26.COV2.S at 5x1010 vp followed by a dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV-2 rS vaccine with 50 mcg Matrix-M); 2) Group 2E - previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed by a 100-mcg dose of mRNA-1273, Group 5E - previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed by a 5x10^10 vp dose of Ad26.COV2.S, Group 8E - previously EUA-dosed vaccination with Moderna

• mRNA-1273 at 100 mcg for two doses followed by a 30-mcg dose of BNT162b2, Group 13E - previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed by a 50-mcg dose of mRNA-1273; Group 16E - previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed by a dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV2 rS vaccine with 50 mcg Matrix-M); 3) Group 3E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 100-mcg dose of mRNA-1273. Group 6E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 5x10^10 vp dose of Ad26.COV2.S, Group 9E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 30-mcg dose of BNT162b2, Group 11E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 100-mcg dose of mRNA-1273.211. Group 14E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 50-mcg dose of mRNA-1273, Group 17E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV2 rS vaccine with 50 mcg Matrix-M).

A telephone visit will occur at Day 8 and in-person follow-up visits will occur on Days 15 and 29, as well as 3, 6, and 12 months after the vaccination. Cohort 2 will include approximately 250 participants per group aged >/=18 years of age who have not received a Coronavirus Disease 2019 (COVID-19) vaccine and have no known history of Coronavirus Disease 2019 (COVID-19) or SARS Coronavirus 2 (SARS-CoV-2) infection. They will be assigned to receive COVID-19 vaccine under Emergency Use Authorization dosing (EUA) (two vaccinations of mRNA-1273 at the 100mcg dose at a 28 days of interval). These pools of participants will be assigned 50 mcg mRNA-1273 at a minimum of 12 weeks following receipt of EUA dosing and followed through 12 months after the last vaccination. A telephone visit will occur one week after each primary EUA vaccination and one week after the booster dose. In person follow-up visits will occur on 14 days following completion of EUA vaccinations and on days 14, and 28 days after the booster dose, as well as 3, 6, and 12 months post the booster vaccination. Additional pools of subjects can be included if needed as additional COVID-19 vaccines are awarded EUA.

New groups may be added to Cohort 1 or 2 dependent upon manufacture of variant lineage spike protein-based vaccine constructs or vaccines newly awarded EUA. The primary objectives of this study are 1) to evaluate the safety and reactogenicity of delayed heterologous or homologous vaccine doses after EUA dosed vaccines, and 2) to evaluate the breadth of the humoral immune responses of heterologous and homologous delayed boost regimens following EUA dosing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 867
• Est. completion date: June 16, 2023
• Est. primary completion date: June 16, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible to participate in this study:

1. Individuals >/= 18 years of age at the time of consent.

2. Received and completed primary mRNA COVID-19 vaccine under EUA dosing guidelines and one or two doses of Ad26.COV2.S at least 12 weeks prior to enrollment (Cohort 1 only).

3. Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures.

4. Determined by medical history, targeted physical examination and clinical judgement of the investigator to be in good health.*

• Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included.

5. Female participants of childbearing potential may be enrolled in the study, if all of the following apply:

• Practiced adequate contraception for 28 days prior to the first dose of vaccine (Day 1),

• Has agreed to continue adequate contraception through 3 months following the booster dose,

• Has a negative pregnancy test at screening and on the day of the first study vaccine dose (Day 1),

• Is not currently breastfeeding.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from the study:

1. Known history of SARS-CoV-2 infection. (for Cohort 1 and the primary series of Cohort 2).

2. Prior administration of an investigational coronavirus (SARS Coronavirus (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV)) vaccine or SARS Coronavirus 2 (SARS-CoV-2) monoclonal antibody in the preceding 90 days or current/planned simultaneous participation in another interventional study.

3. Receipt of SARS Coronavirus 2 (SARS-CoV-2) vaccine prior to study entry (Cohort 2 only).

4. A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine or nanolipid particles.

5. Receipt of any investigational study product within 28 days prior to enrollment.

6. Received or plans to receive a vaccine within 28 days prior to the first dose (Day 1) or plans to receive a non-study vaccine within 28 days prior to or after any dose of study vaccine (with exception for seasonal influenza vaccine within 14 days of study vaccine).

7. Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular injections or blood draws, or previously experienced thrombosis with thrombocytopenia (TTS) or heparin-induced thrombocytopenia.

8. Current or previous diagnosis of immunocompromising condition, immune-mediated disease, or other immunosuppressive condition.

9. Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids >/= 20 milligram per day of prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to Day 1.

10. Received immunoglobulin, blood-derived products, within 90 days prior to first study vaccination.

11. An immediate family member or household member of this study's personnel.

12. Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as >/= 38.0 degrees Celsius or 100.4 degrees 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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• Ad26.COV2.S
Formulated to contain 5x10 virus particles of the Ad26 vector encoding the S glycoprotein of SARS-CoV-2. Each dose of the Ad26.COV2.S vaccine also includes sodium chloride, citric acid monohydrate, trisodium citrate dihydrate, polysorbate-80, 2-hydroxypropyl-ß-cyclodextrin, and ethanol. Ad26.COV2.S will be used undiluted to obtain the specified vp content in 0.5 mL doses. Each dose is 0.5 mL.
• BNT162b2
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2. Each vial contains up to six doses. BNT162b2 (250 mcg/0.5 mL) will be administered in diluted 0.3 mL doses (30 mcg/0.3 mL).
• mRNA-1273
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV).
• mRNA-1273.211
Lipid nanoparticle (LNP) dispersion containing 1:1 mix of mRNAs that encodes for the prefusion stabilized S protein of the B.1.351 variant SARS-CoV-2 strain and the prefusion stabilized S protein of the Wuhan-Hu-1 strain used in mRNA-1273. mRNA-1273.211 (0.2 mg/mL) will be administered in 0.5 mL doses (100 mcg/0.5 mL).
• mRNA-1273.222
Formulated in the same way as the mRNA-1273 vaccine but contains 1:1 mix of mRNAs that encodes for the prefusion stabilized S protein of the Omicron BA.4/BA.5 variant SARS-CoV-2 strain and the prefusion stabilized S protein of the Wuhan-Hu-1 strain used in mRNA-1273.
• SARS-CoV-2 rS/M1
SARS-CoV-2 rS Drug Substance containing the prototype Wuhan is formulated with saponin-based Matrix-M adjuvant in a buffer of 25 mM sodium phosphate (pH 7.2), 300 mM sodium chloride, and 0.01% (weight per volume [w/v]) polysorbate 80. NVX-Co-V2373 will be administered in 0.5 mL dose (5 mcg Prototype SARS-CoV-2 rS with 50 mcg Matrix-M adjuvant)

Locations

Country	Name	City	State
United States	University of Maryland Baltimore - Institute of Human Virology	Baltimore	Maryland
United States	Cincinnati Children's Hospital Medical Center Vaccine Research Center	Cincinnati	Ohio
United States	The Hope Clinic of Emory University	Decatur	Georgia
United States	University of Texas Medical Branch	Galveston	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	NYU Grossman Long Island School of Medicine - Vaccine Center	New York	New York
United States	University of Pittsburgh - Medicine - Infectious Diseases	Pittsburgh	Pennsylvania
United States	University of Rochester Medical Center - Vaccine Research Unit	Rochester	New York
United States	Kaiser Permanente Washington Health Research Institute	Seattle	Washington
United States	The University of Washington - Virology Research Clinic	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Magnitude of SARS-CoV-2 specific antibody binding and neutralization titers	Estimated by 95% confidence intervals (CI) for the geometric mean titer (GMT) at each timepoint when samples are collected.	Day 1 through 12 months post-boost dose
Primary	Occurrence of adverse events (AEs)	Post any vaccination/boost	Day 1 through 28 days post dose
Primary	Occurrence of Adverse Events of Special Interest (AESIs).		Day 1 through study completion (approximately 12 months for cohort 1 and for those cohort 2 individuals not receiving a second boost and approximately 6 months after second boost for individuals in cohort 2).
Primary	Occurrence of New-Onset Chronic Medical Condition (NOCMCs).		Day 1 through study completion (approximately 12 months for cohort 1 and for those cohort 2 individuals not receiving a second boost and approximately 6 months after second boost for individuals in cohort 2).
Primary	Occurrence of Related Medically attended adverse events (MAAEs).		Day 1 through study completion (approximately 12 months for cohort 1 and for those cohort 2 individuals not receiving a second boost and approximately 6 months after second boost for individuals in cohort 2).
Primary	Occurrence of Serious Adverse Events (SAEs).		Day 1 through study completion (approximately 12 months for cohort 1 and for those cohort 2 individuals not receiving a second boost and approximately 6 months after second boost for individuals in cohort 2).
Primary	Occurrence of solicited reactogenicity adverse events (AEs)	Systemic solicited reactogenicity adverse events (AEs) will be assessed.	Through 7 days post boose dose
Primary	Occurrence of solicited reactogenicity adverse events (AEs)	Local solicited reactogenicity adverse events (AEs) will be assessed.	Through 7 days post-boost dose
Primary	Response rate of SARS-CoV-2 specific antibody binding and neutralization titers	Estimated by 95% confidence intervals (CI) for the geometric mean titer (GMT) at each timepoint when samples are collected.	Day 1 through 12 months post-boost dose