Chimpanzee Adenovirus and Self-Amplifying mRNA Prime-Boost Prophylactic Vaccines Against SARS-CoV-2 in Healthy Adults

Summary

This is a multicenter, US-only, phase 1, open-label, dose escalation, non-randomized study of the safety, tolerability, and immunogenicity of investigational ChAd and SAM SARS-CoV-2 vaccines in healthy adult subjects. Homologous and heterologous prime-boost vaccination schedules (Stage 1), as well as boost(s) after receipt of COVID-19 EUA/licensed vaccines (Stage 2) will be examined. Subjects' willingness to receive ChAd vaccines will be assessed and documented at the time of informed consent and considered to determine group assignments. This phase 1 study will enroll 17 Stage 1 and up to 118 Stage 2 subjects. Eligible subjects will be enrolled in different groups based on their age (18-60 years old and \>60 years old) and their EUA/licensed COVID-19 vaccination status. A sentinel approach with 72-hour (Stage 1, and Stage 2, Groups 5, 6, 8-10, 12, 13-15) or 7-day observation times (Groups 7 and 11) will be used, before recruiting the remainder of each dose escalation group. Decisions about dose escalation will be determined by the SSC with consultation with the DSMB as needed after all subjects in each group have been observed through Day 8 post first study vaccination. All subjects will be followed through 12 months after their last study vaccination. Vaccinated subjects will be carefully monitored for exposure and infection to SARS-CoV-2 throughout the study. Escalation to the highest dose (10 µg) of SAM-S-TCE in younger subjects will proceed only following safety assessments of the 10 µg dose in older subjects for a period of 28 days post-vaccination. In addition, the dosage of SAM-S-TCE given as a double boost to subjects previously vaccinated with the Johnson \& Johnson/Janssen Ad26 COVID-19 EUA/licensed vaccine in Groups 8A, 8B, and 12A, 12B will be determined based on the dose escalation reactogenicity and immunogenicity results in Groups 5-7 and 9-11, respectively. After protocol version 9.0 was implemented, it was decided not to enroll subjects into Groups 7 and 8 because of competing priorities and predicted difficulties enrolling into these two groups.

The primary objectives of this study are 1) To assess the safety and tolerability of different doses of ChAd-S or ChAd-S-TCE, and SAM-S or SAM-S-TCE when administered as prime-boost in healthy naïve adult subjects, 2) To assess the safety and tolerability of different doses of ChAd-S or ChAd-S-TCE, and SAM-S or SAM-S-TCE when administered as first or second boost in healthy adult subjects previously vaccinated with an mRNA or adenoviral-vectored COVID-19 EUA/licensed vaccine.

Conditions

• COVID-19

Interventions

BIOLOGICAL

ChAdV68-S

Chimpanzee Adenovirus serotype 68 - Spike (ChAdV68-S) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

BIOLOGICAL

ChAdV68-S-TCE

Chimpanzee Adenovirus 68 - Spike plus additional SARS-CoV-2 T cell epitopes (ChAdV68-S-TCE) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5- or 1.0-mL (depending on dose level) intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

BIOLOGICAL

SAM-LNP-S

Self-Amplifying mRNA - Lipid Nanoparticles - Spike (SAM-LNP-S) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.25 mL or 0.5 mL (depending on dose level) intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

BIOLOGICAL

SAM-LNP-S-TCE

Self-Amplifying mRNA - Lipid Nanoparticles -Spike plus additional SARS-CoV-2 T cell epitopes (SAM-S-TCE) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.25 or 0.5 mL (depending on dose level) intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

OTHER

Sodium Chloride, 0.9%

The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Sponsors & Collaborators

• Gritstone bio, Inc.

  collaborator INDUSTRY

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Study Design

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-03-25

Primary Completion

2023-09-15

Completion

2023-09-15

FDA Drug

Yes

Countries

• United States

Study Locations