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-19 Using Different Dosing Regimens in Healthy and Immunocompromised Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Infections, Respiratory
- Sponsor
- BioNTech SE
- Enrollment
- 512
- Locations
- 2
- Primary Endpoint
- The Percentage of Participants With at Least 1 Unsolicited Treatment Emergent Adverse Event (TEAE) Occurring After Dose 1 (Prime Immunization) up to Dose 2 (Boost Immunization) or 28 Days After Dose 1.
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
Originally, the study was planned to include two parts, i.e., Part A and Part B, however Part B was cancelled due to changes in the overall clinical development plan. 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).
The conducted Part A was a dose-finding part to investigate the optimal dose of four different vaccines (BNT162a1, BNT162b1, BNT162b2, and BNT162c2), allowing dose adjustments upwards and downwards in younger participants. Doses tested in older participants and expansion cohorts were chosen based on acceptability of dosing in younger participants.
The vaccines BNT162a1, BNT162b1, BNT162b2, and BNT162c2 were administered using a Prime/Boost (P/B) regimen with two doses given ~21 days apart. The vaccine BNT162c2 was also administered using a Single dose (SD) regimen. Four additional expansion cohorts (cohorts 11, 12, 13, and 14) aged from 18 to 85 years received BNT162b2 using a P/B regimen only. In cohort 11, participants received BNT162b2 using one 3 μg prime dose (Dose 1) and one 30 μg boost dose (Dose 2) of BNT162b2. Participants in cohorts 12, 13, and 14 received two doses of BNT162b2 30 µg, each.
Detailed Description
This study was a multi-site, Phase I/II, open-label, dose-escalation study. The study included the first-in-human (FIH) dose and dose ranging groups for all four vaccines in healthy younger participants (aged 18 to 55 years \[years\]) and older participants (aged 56 to 85 years). The conducted Part A followed a dose escalation design. Discretionary dose de-escalation and refinement was also planned. Study participants with the FIH immunization and any subsequent dose escalation cohorts were immunized using a sentinel dosing/subject staggering. For any dose de-escalation or dose-refinement cohorts in younger adults, i.e., cohorts with doses lower than previously tested, participants were dosed using a subject staggering process. Cohorts in older participants were optional and dependent on acceptability of dosing in younger participants. Part A consisted of a treatment phase and a follow-up phase. For the BNT162a1 3 µg arm, the Safety Review Committee (SRC) decided to stop dosing after 6 treated participants and to not administer the boost immunization (Dose 2). For the BNT162b1 60 µg arm, the SRC decided to not administer the boost immunization (Dose 2) for the 12 participants.
Investigators
Eligibility Criteria
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
- •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
- •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
- •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
- •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
- •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
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
- •Had administration of any immunoglobulins and/or any blood products within the 3 months prior to Visit
- •Had administration of another investigational medicinal product including vaccines within 60 days or 5 half-lives (whichever is longer), prior to Visit
- •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
Outcomes
Primary Outcomes
The Percentage of Participants With at Least 1 Unsolicited Treatment Emergent Adverse Event (TEAE) Occurring After Dose 1 (Prime Immunization) up to Dose 2 (Boost Immunization) or 28 Days After Dose 1.
Time Frame: 28 days following Dose 1 or up to Dose 2 (whichever was first)
TEAEs without AEs based on solicited reporting via diaries, were analyzed by vaccine, age group, dose level, and for each IMP dose. The percentage of participants reporting at least one TEAE was summarized by adverse event types (any TEAE and any grade \>=3 TEAE) using the Safety Set.
Number of Participants With Solicited Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling) Recorded up to 7 Days After Each IMP Dose.
Time Frame: From Day 1 to Day 8 for Dose 1 (Prime Immunization) and from Day 22 to Day 29 for Dose 2 (Boost Immunization)
Solicited local reactions at the injection site (pain, tenderness, erythema/redness, and induration/swelling) were monitored and graded using criteria based on the guidance given in US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials". The reporting of local reactions was based on the participant's assessments via daily solicited reports in the participant diaries.
The Percentage of Participants With at Least 1 Unsolicited TEAE Occurring After Dose 1 up to 28 Days After Dose 2 (Boost Immunization) or After Dose 1 (Prime Immunization) (if no Dose 2)
Time Frame: 28 days following Dose 2 or Dose 1 (if no Dose 2 was given)
TEAEs, without AEs based on solicited reporting via diaries, were analyzed by vaccine, age group, dose level, and for each IMP dose. The percentage of participants reporting at least one TEAE was summarized by adverse event types (any TEAE and any grade \>=3 TEAE) using the Safety Set.
Number of Participants With Solicited Systemic Reactions (Nausea, Vomiting, Diarrhea, Headache, Fatigue, Myalgia, Arthralgia, Chills, Loss of Appetite, Malaise, and Fever) Recorded up to 7 Days After Each IMP Dose.
Time Frame: From Day 1 to Day 8 for Dose 1 (Prime Immunization) and from Day 22 to Day 29 for Dose 2 (Boost Immunization)
Solicited systemic reactions (nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever) were monitored and graded using criteria based on the guidance given in US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials". The reporting of systemic reactions was based on the participant's assessments via daily solicited reports in the participant diaries.
Secondary Outcomes
- Fold Increase in Functional Antibody Titers as Compared to Baseline for BNT162a1, BNT162b1, BNT162b2 (Younger and Older Dose Ranging Cohorts), and BNT162c2 (P/B)(up to 183 days following Dose 1)
- Functional Antibody Responses (Titers) for BNT162c2 (SD)(up to 183 days following Dose 1)
- Fold Increase in Functional Antibody Titers as Compared to Baseline for BNT162c2 (SD)(up to 183 days following Dose 1)
- Number of Participants With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline for BNT162c2 (SD)(up to 183 days following Dose 1)
- Fold Increase in Functional Antibody Titers as Compared to Baseline for BNT162b2 (Expansion Cohorts 11, 12, 13, and 14; P/B)(up to 1 year following Dose 1)
- Number of Participants With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline for BNT162b2 (Expansion Cohorts 11, 12, 13, and 14; P/B)(up to 1 year following Dose 1)
- Number of Participants With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline for BNT162a1, BNT162b1, BNT162b2 (Younger and Older Dose Ranging Cohorts), and BNT162c2 (P/B)(up to 183 days following Dose 1)
- Functional Antibody Responses (Titers) for BNT162b2 (Expansion Cohorts 11, 12, 13, and 14; P/B)(up to 1 year following Dose 1)
- Functional Antibody Responses (Titers) for BNT162a1, BNT162b1, BNT162b2 (Younger and Older Dose Ranging Cohorts), and BNT162c2 (P/B)(up to 183 days following Dose 1)