Study to Describe the Safety, Tolerability, Immunogenicity, and Potential Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Adults

• ClinicalTrials.gov Identifier: NCT04368728
• Recruitment Status: Recruiting
• First Posted: April 30, 2020
• Last Update Posted: May 14, 2020
• Sponsor: Biontech SE
• Collaborator: Pfizer
• Information provided by (Responsible Party): Biontech SE

Study Description

Brief Summary:

This is a Phase 1/2, randomized, placebo-controlled, observer-blind, dose-finding, and vaccine candidate-selection study in healthy adults.

The study will evaluate the safety, tolerability, immunogenicity, and potential efficacy of up to 4 different SARS-CoV-2 RNA vaccine candidates against COVID-19:

• As a 2-dose or single-dose schedule
• At up to 3 different dose levels
• In 3 age groups (18 to 55 years of age, 65 to 85 years of age, and 18 to 85 years of age

The study consists of 3 stages. Stage 1: to identify preferred vaccine candidate(s), dose level(s), number of doses, and schedule of administration (with the first 15 participants at each dose level of each vaccine candidate comprising a sentinel cohort); Stage 2: an expanded-cohort stage; and Stage 3; a final candidate/dose large-scale stage.

Condition or disease	Intervention/treatment	Phase
SARS-CoV-2 Infection; COVID-19	Biological: BNT162a1; Biological: BNT162b1; Biological: BNT162b2; Biological: BNT162c2; Other: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 7600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A PHASE 1/2, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING STUDY TO DESCRIBE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND POTENTIAL EFFICACY OF SARS-COV-2 RNA VACCINE CANDIDATES AGAINST COVID-19 IN HEALTHY ADULTS
• Actual Study Start Date: April 29, 2020
• Estimated Primary Completion Date: August 11, 2021
• Estimated Study Completion Date: March 8, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low-dose, 18-55 years of age (Single dose)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Mid-dose, 18-55 years of age (Single dose)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: High-dose, 18-55 years of age (Single dose)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Low-dose, 65-85 years of age (Single dose)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Mid-dose, 65-85 years of age (Single dose)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: High-dose, 65-85 years of age (Single dose)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Low-dose, 18-55 years of age (2 doses)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Mid-dose, 18-55 years of age (2 doses)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: High-dose, 18-55 years of age (2 doses)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Low-dose, 65-85 years of age (2 doses)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Mid-dose, 65-85 years of age (2 doses)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: High-dose, 65-85 years of age (2 doses)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Low-dose, 18-85 years of age (Single dose)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Mid-dose, 18-85 years of age (Single dose)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: High-dose, 18-85 years of age (Single dose)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Low-dose, 18-85 years of age (2 doses)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: Mid-dose, 18-85 years of age (2 doses)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Experimental: High-dose, 18-85 years of age (2 doses)	Biological: BNT162a1; 0.5 mL intramuscular injection; Biological: BNT162b1; 0.5 mL intramuscular injection; Biological: BNT162b2; 0.5 mL intramuscular injection; Biological: BNT162c2; 0.5 mL intramuscular injection
Placebo Comparator: Placebo, 18-55 years of age	Other: Placebo; 0.5 mL Intramuscular injection
Placebo Comparator: Placebo, 65-85 years of age	Other: Placebo; 0.5 mL Intramuscular injection
Placebo Comparator: Placebo, 18-85 years of age	Other: Placebo; 0.5 mL Intramuscular injection

Outcome Measures

Primary Outcome Measures :

1. Percentage of participants reporting local reactions [ Time Frame: For 7 days after dose 1 and dose 2 ]
   Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
2. Percentage of participants reporting systemic events [ Time Frame: For 7 days after dose 1 and dose 2 ]
   Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
3. Percentage of participants reporting adverse events [ Time Frame: From dose 1 through 1 month after the last dose ]
   As elicited by investigational site staff
4. Percentage of participants reporting serious adverse events [ Time Frame: From dose 1 through 6 months after the last dose ]
   As elicited by investigational site staff
5. Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values [ Time Frame: 1 day after dose 1 ]
   As measured at the central laboratory
6. Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values [ Time Frame: 7 days after dose 1 ]
   As measured at the central laboratory
7. Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values [ Time Frame: 7 days after dose 2 ]
   As measured at the central laboratory
8. Percentage of sentinel cohort participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between baseline and 1 day after dose 1 ]
   As measured at the central laboratory
9. Percentage of sentinel cohort participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between baseline and 7 days after dose 1 ]
   As measured at the central laboratory
10. Percentage of sentinel cohort participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between before dose 2 and 7 days after dose 2 ]
    As measured at the central laboratory

Secondary Outcome Measures :

1. SARS-CoV-2-specific WT serum neutralizing antibody levels, expressed as GMTs [ Time Frame: Through 2 years after the final dose ]
   As measured at the central laboratory
2. GMFR in SARS-CoV-2-specific WT serum neutralizing titers from before vaccination to each subsequent time point [ Time Frame: Through 2 years after the final dose ]
   As measured at the central laboratory
3. Proportion of participants achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2-specific WT serum neutralizing antibody levels [ Time Frame: Through 2 years after the final dose ]
   As measured at the central laboratory
4. SARS-CoV-2--spike protein-specific binding antibody levels and RBD-specific binding antibody levels, expressed as GMCs [ Time Frame: Through 2 years after the final dose ]
   As measured at the central laboratory
5. Proportion of participants achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2--spike protein-specific binding antibody levels and RBD-specific binding antibody levels [ Time Frame: Through 2 years after the final dose ]
   As measured at the central laboratory
6. GMFR in SARS-CoV-2-spike protein-specific binding antibody levels and RBD-specific binding antibody levels from before vaccination to each subsequent time point [ Time Frame: Through 2 years after the final dose ]
   As measured at the central laboratory
7. GMR of the geometric mean of SARS-CoV-2-specific WT serum neutralizing titers to the geometric mean of SARS CoV 2 (spike protein and RBD) specific binding antibody levels [ Time Frame: Through 2 years after the final dose ]
   As measured at the central laboratory
8. Confirmed COVID-19 incidence [ Time Frame: From the last dose of study intervention to the end of the study, up to 2 years ]
   Per 1000 person-years of follow-up

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male or female participants between the ages of 18 and 55 years, inclusive, 65 and 85 years, inclusive, or 18 and 85 years, inclusive, at randomization (dependent upon study stage).
• Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
• Healthy participants who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study.
• Capable of giving personal signed informed consent

Exclusion Criteria:

• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
• Receipt of medications intended to prevent COVID 19.
• Stages 1 and 2 only: Previous clinical or microbiological diagnosis of COVID 19.

• Sentinel participants in Stage 1 only: Individuals at high risk for severe COVID-19, including those with any of the following risk factors:

  • Hypertension
  • Diabetes mellitus
  • Chronic pulmonary disease
  • Asthma
  • Current vaping or smoking
  • History of chronic smoking within the prior year
  • BMI >30 kg/m2
  • Anticipating the need for immunosuppressive treatment within the next 6 months
• Sentinel participants in Stage 1 only: Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention.
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• Women who are pregnant or breastfeeding.
• Previous vaccination with any coronavirus vaccine.
• Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
• Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
• Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
• Previous participation in other studies involving study intervention containing lipid nanoparticles.
• Sentinel participants in Stage 1 only: Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at the screening visit.
• Sentinel participants in Stage 1 only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality.
• Sentinel participants in Stage 1 only: Positive test for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBc Abs), or hepatitis C virus antibodies (HCV Abs) at the screening visit.
• Sentinel participants in Stage 1 only: SARS-CoV-2 NAAT-positive nasal swab within 24 hours before receipt of study intervention.
• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Contacts and Locations

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

Locations

United States, Maryland

University of Maryland General Clinical Research Center; Recruiting

Baltimore, Maryland, United States, 21201

University of Maryland Medical Center Investigational Drug Service Pharmacy; Recruiting

Baltimore, Maryland, United States, 21201

University of Maryland, Center for Vaccine Development and Global Health; Recruiting

Baltimore, Maryland, United States, 21201

United States, New York

NYU Langone Health; Recruiting

New York, New York, United States, 10016

Rochester Regional Health/Rochester General Hospital; Recruiting

Rochester, New York, United States, 14621

United States, Ohio

Cincinnati Children's Hospital Medical Center; Recruiting

Cincinnati, Ohio, United States, 45206

Cincinnati Children's Hospital Medical Center; Recruiting

Cincinnati, Ohio, United States, 45229-3039

Sponsors and Collaborators

Biontech SE

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Biontech SE
• ClinicalTrials.gov Identifier: NCT04368728
• Other Study ID Numbers: C4591001
• First Posted: April 30, 2020
• Last Update Posted: May 14, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Biontech SE:

COVID-19; Coronavirus; Vaccine; SARS-CoV-2; RNA Vaccine