A Trial Investigating the Safety and Effects of Four BNT162 Vaccines Against COVID-2019 in Healthy and Immunocompromised Adults

January 12, 2022 updated by: BioNTech SE

A Multi-site, Phase I/II, 2-Part, Dose-Escalation Trial Investigating the Safety and Immunogenicity of Four Prophylactic SARS-CoV-2 RNA Vaccines Against COVID-2019 Using Different Dosing Regimens in Healthy and Immunocompromised Adults

This trial has two parts. Part A and Part B. Due to changes in the overall clinical development plan, Part B will no longer be conducted. The objectives originally described for Part B have been implemented in the ongoing development via a pivotal Phase I/II/III trial BNT162-02/C4591001 (ClinicalTrials.gov NCT: 04368728).

Part A is for dose ranging of four different vaccines (BNT162a1, BNT162b1, BNT162b2, and BNT162c2) which will be undertaken with dose escalation and de-escalation plus the evaluation of interim dose levels. It also includes dose ranging in older participants.

The vaccines BNT162a1, BNT162b1, BNT162b2, and BNT162c2 will be administered using a Prime/Boost (P/B) regimen. The vaccine BNT162c2 will also be administered using a Single dose (SD) regimen. Three additional cohorts aged from 18 to 85 years receiving BNT162b2 only.

BNT162b2 has entered a Phase II/III evaluation of efficacy, with the intent to support an application for marketing authorization. The dosing regimen under investigation is two BNT162b2 doses given ~21 d apart.

Study Overview

Study Type

Interventional

Enrollment (Actual)

512

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Berlin, Germany
        • Contract Research Organization
      • Frankfurt am Main, Germany
        • Universitäts Klinikum
      • Heidelberg, Germany
        • Universitäts Klinikum
      • Kiel, Germany
        • Contract Research Organization
      • Mannheim, Germany
        • Contract Research Organization

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Have given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
  • They must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions (e.g., to practice social distancing and to follow good practices to reduce their chances of being infected or spreading COVID-19), and other requirements of the trial.
  • They must be able to understand and follow trial-related instructions.
  • For younger adult cohorts, volunteers must be aged 18 to 55 years, have a body mass index (BMI) over 19 kg/m^2 and under 30 kg/m^2, and weigh at least 50 kg at Visit 0. OR For older adult cohorts, volunteers must be aged 56 to 85 years, have a BMI over 19 kg/m^2 and under 30 kg/m^2, and weigh at least 50 kg at Visit 0. OR For the immunocompromised adult cohort (Cohort 13), volunteers must be aged 18 to 85 years, have a BMI over 19 kg/m^2 and under 30 kg/m^2, and weigh at least 50 kg at Visit 0.
  • They must be healthy, in the clinical judgment of the investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs (systolic/diastolic blood pressure, pulse rate, body temperature, respiratory rate), and clinical laboratory tests (blood chemistry, hematology, and urine chemistry) at Visit 0. 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. OR For the immunocompromised cohort (Cohort 13); volunteers who have previously received solid organ transplant, or peripheral blood stem cell transplantation ≥6 months after transplantation, or individuals with human immunodeficiency virus (HIV) infection with a CD4+ T-cell count of ≥200 x 10^6 /L at Visit 0. Individuals with lower T-cell counts will be excluded from the trial on the basis that this represents a significant medical complication. In the clinical judgment of the investigator, volunteers must be immunocompromised but otherwise healthy. After consultation with the Medical Monitor, this may include individuals receiving immunosuppressant therapy due to another confounding disease at least 2 weeks prior to enrollment and/or at least 6 weeks following immunization with BNT162b2, and/or individuals with immunosuppressive treatment of an autoimmune disease if the disease is stable.
  • Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin urine test at Visit 0 and Visit 1. Women that are postmenopausal or permanently sterilized will be considered as not having reproductive potential.
  • WOCBP must agree to practice a highly effective form of contraception during the trial, starting after Visit 0 and continuously until 60 days after receiving the last immunization. WOCBP must agree to require their male partners to use condoms during sexual contact (unless male partners are sterilized or infertile).
  • WOCBP must confirm that they practice at least one highly effective form of contraception for the 14 days prior to Visit 0.
  • WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial, starting after Visit 0 and continuously until 60 days after receiving the last immunization.
  • Men who are sexually active with a WOCBP and have not had a vasectomy must agree to practice a highly effective form of contraception with their female partner of childbearing potential during the trial, starting after Visit 0 and continuously until 60 days after receiving the last immunization.
  • Men must be willing to refrain from sperm donation, starting after Visit 0 and continuously until 60 days after receiving the last immunization.
  • They must have confirmation of their health insurance coverage prior to Visit 0.
  • They must agree to not be vaccinated during the trial, starting after Visit 0 and continuously until 28 days after receiving the last immunization.

Exclusion Criteria:

  • Have had any acute illness, as determined by the investigator, with or without fever, within 72 hours prior to the first immunization. An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the investigator, the residual symptoms will not compromise their well-being if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments.
  • Are breastfeeding on the day of Visit 0 or who plan to breastfeed during the trial, starting after Visit 0 and continuously until at least 90 days after receiving the last immunization.
  • Have a known allergy, hypersensitivity, or intolerance to the planned investigational medicinal product (IMP) including any excipients of the IMP.
  • Had any medical condition or any major surgery (e.g., requiring general anesthesia) within the past 5 years which, in the opinion of the investigator, could compromise their well-being if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments.
  • Have any surgery planned during the trial, starting after Visit 0 and continuously until at least 90 days after receiving the last immunization.
  • Had any chronic use (more than 21 continuous days) of any systemic medications, including immunosuppressant's or other immune-modifying drugs (except for Cohort 13), within the 6 months prior to Visit 0 unless in the opinion of the investigator, the medication would not prevent, limit, or confound the protocol-specified assessments or could compromise subject safety. 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.
  • Had any vaccination within the 28 days prior to Visit 0.
  • Had administration of any immunoglobulins and/or any blood products within the 3 months prior to Visit 0.
  • Had administration of another investigational medicinal product including vaccines within 60 days or 5 half-lives (whichever is longer), prior to Visit 0.
  • Have a known history of active or ongoing hepatitis B or hepatitis C infection; or except for Cohort 13: HIV-1 or HIV-2 infection within the 30 days prior to Visit 0.
  • Have a positive polymerase chain reaction (PCR)-based test for SARS-CoV-2 within the 30 days prior to Visit 1.
  • Have a positive drugs of abuse (for amphetamines, benzodiazepines, barbiturates, cocaine, cannabinoids, opiates, methadone, methamphetamines, phencyclidine, and tricyclic antidepressants) result at Visit 0 or Visit 1.
  • Have a positive breath alcohol test at Visit 0 or Visit 1.
  • Previously participated in an investigational trial involving lipid nanoparticles.
  • Are subject to exclusion periods from other investigational trials or simultaneous participation in another clinical trial. When entering the follow-up phase, i.e., after completing the end of treatment (EoT) visit, subjects are allowed to participate in other clinical trials not investigating COVID-19 vaccines or treatments; subjects immunized with BNT162 vaccines in this clinical trial are allowed to participate in other clinical trials involving immunization with BNT162b2.
  • Have any affiliation with the trial site (e.g., are close relative of the investigator or dependent person, such as an employee or student of the trial site).
  • Have a history (within the past 5 years) of substance abuse or known medical, psychological, or social conditions which, in the opinion of the investigator, could compromise their well-being if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments.
  • Have a history of hypersensitivity or serious reactions to previous vaccinations.
  • Have a history of Guillain-Barré Syndrome within 6 weeks following a previous vaccination.
  • Have a history of narcolepsy.
  • Have history of alcohol abuse or drug addiction within 1 year before Visit 0.
  • (Except for Cohort 13) Have a history of or suspected immunosuppressive condition, acquired or congenital, as determined by medical history and/or physical examination at Visit 0.
  • Have any abnormality or permanent body art (e.g., tattoo) that, in the opinion of the investigator, would obstruct the ability to observe local reactions at the injection site.
  • Have had any blood loss >450 mL, e.g., due to donation of blood or blood products or injury, within the 7 days prior to Visit 0 or plan to donate blood during the trial, starting after Visit 0 and continuously until at least 7 days after receiving the last immunization.
  • Have symptoms of COVID-19, e.g., respiratory symptoms, fever, cough, shortness of breath and breathing difficulties.
  • Have had contact with persons diagnosed with COVID-19 or who tested positive for SARS-CoV-2 by any diagnostic test within the 30 days prior to Visit 1.
  • Are soldiers, volunteers in detention, contract research organization (CRO) or sponsor staff or their family members.
  • Regular receipt of inhaled/nebulized corticosteroids (except for Cohort 13).
  • For older volunteers and for Cohort 13 only: Have a condition known to put them at high risk for severe COVID-19, including those with any of the following risk factors:
  • Uncontrolled hypertension.
  • Diabetes mellitus (HbA1c >8.5% ≥3 months, according to the medical history reported by the subject).
  • Chronic obstructive pulmonary disease.
  • Asthma.
  • Chronic liver disease.
  • Known Stage 3 or worse chronic kidney disease (glomerular filtration rate <60 mL/min/1.73 m^2); Except for post-renal transplant patients who should have (estimated) GFR ≥40 mL/min/1.73 m^2.
  • Serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies.
  • Sickle cell disease.
  • Cancer (except for Cohort 13).
  • Are immune compromised due to stem cell or organ-transplantation with significant medical complications such as acute or chronic graft rejection or graft versus host disease requiring intensive immunosuppressive treatment, transplant failure or infectious complications or other conditions that would be considered a contraindication for vaccination.
  • Are immune compromised due to HIV infection with a CD4+ count of < 200 x 10^6 /L at screening or significant medical complications such as opportunistic infections, malignant complications (e.g., lymphoma, Kaposi sarcoma), other organ manifestations consistent with advanced AIDS or other conditions that would be considered a contraindication for vaccination.
  • Resident in a long term facility.
  • Current vaping or smoking (occasional smoking is acceptable).
  • History of chronic smoking within the prior year.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BNT162a1 (P/B) - Part A 18-55 years of age
Escalating dose levels
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Experimental: BNT162b1 (P/B) - Part A 18-55 years of age
Escalating dose levels
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Experimental: BNT162b2 (P/B) - Part A 18-55 years of age
Escalating dose levels
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Experimental: BNT162c2 (P/B) - Part A 18-55 years of age
Escalating dose levels
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Experimental: BNT162c2 (prime only) - Part A 18-55 years of age
Single dose
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Experimental: BNT162b1 (P/B) - Part A 56-85 years of age
Escalating dose levels
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Experimental: BNT162b2 (P/B) - Part A 56-85 years of age
Escalating dose levels
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Experimental: BNT162b2 (P/B) - Part A 18-85 years of age (Expansion cohorts 11 to 13)
Escalating dose levels
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Experimental: BNT162b2 (P/B) - Part A 18-85 years of age (Expansion cohort 14)
Biomarker (B cell and plasma cell immunity)
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Solicited local reactions at the injection site (pain, tenderness, erythema/redness, induration/swelling) recorded up to 7 days after each immunization.
Time Frame: up to 7 days following each dose administration
up to 7 days following each dose administration
Solicited systemic reactions (nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever) recorded up to 7 days after each immunization.
Time Frame: up to 7 days following each dose administration
up to 7 days following each dose administration
The proportion of subjects with at least 1 unsolicited treatment emergent adverse event (TEAE):
Time Frame: 21 days following dose administration
For BNT162a1, BNT162b1, BNT162b2, and BNT162c2 (P/B): occurring up to 21 days after the prime immunization.
21 days following dose administration
The proportion of subjects with at least 1 unsolicited treatment emergent adverse event (TEAE):
Time Frame: 28 days following dose administration

For BNT162a1, BNT162b1, BNT162b2, and BNT162c2 (P/B): occurring up to 28 days after the boost immunization.

For BNT162c2 (SD): The proportion of subjects with at least 1 unsolicited TEAE occurring up to 28 days after the immunization.

28 days following dose administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
For BNT162a1, BNT162b1, BNT162b2, and BNT162c2 (P/B):
Time Frame: up to 162 days following dose administration
Functional antibody responses (titers) as compared to baseline at 7 and 21 days after primary immunization and at 7, 14, 21, 28, 63, and 162 days after the boost immunization.
up to 162 days following dose administration
For BNT162a1, BNT162b1, BNT162b2, and BNT162c2 (P/B):
Time Frame: up to 162 days following dose administration
Fold increase in functional antibody titers as compared to baseline at 7 and 21 days after primary immunization and at 7, 14, 21, 28, 63, and 162 days after the boost immunization.
up to 162 days following dose administration
For BNT162a1, BNT162b1, BNT162b2, and BNT162c2 (P/B):
Time Frame: up to 162 days following dose administration
Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline at 7 and 21 days after primary immunization and at 7, 14, 21, 28, 63, and 162 days after the boost immunization.
up to 162 days following dose administration
For BNT162c2 (SD):
Time Frame: up to 183 days following dose administration
Functional antibody responses (titers) as compared to baseline at 7, 21, 28, 42, 84, and 183 days after the primary immunization.
up to 183 days following dose administration
For BNT162c2 (SD):
Time Frame: up to 183 days following dose administration
Fold increase in functional antibody titers as compared to baseline at 7, 21, 28, 42, 84, and 183 days after the primary immunization.
up to 183 days following dose administration
For BNT162c2 (SD):
Time Frame: up to 183 days following dose administration
Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline at 7, 21, 28, 42, 84, and 183 days after the primary immunization.
up to 183 days following dose administration
For BNT162b2 (P/B):
Time Frame: up to 162 days following dose administration
Functional antibody responses (titers) as compared to baseline at 7, 14, and 21 days after the primary immunization and at 7, 28, and 162 days after the boost immunization.
up to 162 days following dose administration
For BNT162b2 (P/B):
Time Frame: up to 162 days following dose administration
Fold increase in functional antibody titers as compared to baseline at 7, 14, and 21 days after primary immunization and at 7, 28, and 162 days after the boost immunization.
up to 162 days following dose administration
For BNT162b2 (P/B):
Time Frame: up to 162 days following dose administration
Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline at 7, 14, and 21 days after primary immunization and at 7, 28, and 162 days after the boost immunization.
up to 162 days following dose administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 23, 2020

Primary Completion (Anticipated)

April 1, 2023

Study Completion (Anticipated)

April 1, 2023

Study Registration Dates

First Submitted

May 6, 2020

First Submitted That Met QC Criteria

May 7, 2020

First Posted (Actual)

May 8, 2020

Study Record Updates

Last Update Posted (Actual)

January 13, 2022

Last Update Submitted That Met QC Criteria

January 12, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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