A Phase 1 Trial to Evaluate the Safety, Immunogenicity, and Reactogenicity of a Self-Amplifying mRNA Prophylactic Vaccine Boost Against SARS-CoV-2 in Previously Vaccinated Healthy Adults 18 Years and Older
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 3
- 主要终点
- Change From Baseline in Hemoglobin at Day 8 in Cohorts 3, 4, and 6
研究概览
简要总结
The primary objective was to assess the safety and tolerability of 2 different doses (10 or 30 µg) of GRT-R910 when administered as a boost in healthy adults previously vaccinated with the AstraZeneca, Janssen/Johnson and Johnson, Moderna, or Pfizer/BioNTech Coronavirus disease 2019 (COVID-19) vaccines.
详细描述
This trial studied a self-amplifying messenger ribonucleic acid (samRNA) based vaccine (GRT-R910) in previously vaccinated adults (≥18 years). GRT-R910 uses a codon optimized, prefusion stabilized Spike (S) cassette with additional T cell epitopes (TCEs) covering multiple epitopes from non-spike proteins to safely drive strong, broad, and durable B and T cell immune responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Cohorts 1 and 2, have received AstraZeneca's AZD1222 COVID-19 prime and boost vaccine (Covishield®, Vaxzevria®), with the last dose received at least 2 months or more prior to Day
- •For Cohort 3, have received a primary series of an adenoviral (AstraZeneca AZD1222 [Covishield®, Vaxzevria®] or Janssen [Janssen COVID-19 Vaccine]) COVID-19 vaccine (under emergency supply procedures or upon full approval and may have received booster doses of an authorized vaccine), with the last dose received at least 2 months or more prior to Day
- •For Cohorts 4 and 6, have received a primary series of an mRNA (Pfizer/BioNTech [Comirnaty®] or Moderna [Spikevax®]) COVID-19 vaccine (under emergency supply procedures or upon full approval and may have received booster doses of an authorized vaccine), with the last dose received at least 2 months or more prior to Day
- •Agree to refrain from blood donation during the course of the study.
- •Women of childbearing potential (WOCBP)* must agree to avoid pregnancy and be willing to use a highly effective method of contraception** consistently for 30 days prior to the first study vaccine and for at least 60 days after the last study vaccine
- •Male subjects of childbearing potential must agree to the use of condoms to ensure effective contraception with a female partner from the time of study vaccination until 3 months after vaccination. Male subjects agree to refrain from sperm donation from the time of first vaccination until 3 months after the last vaccination. Male subjects of childbearing potential are biological males who are post-pubertal and considered fertile until permanently sterile by bilateral orchiectomy or vasectomy.
- •Plan to remain living in the area for the duration of the study.
排除标准
- •History of prior confirmed COVID-19 (cohorts 1 and 2).
- •History of prior confirmed (polymerase chain reaction [PCR] or antigen test positive) COVID-19 infection as confirmed by a diagnostic laboratory less than 16 weeks (112 days) prior to enrollment (Cohorts 3, 4, and 6).
- •Positive for SARS-CoV-2 (N-specific) antibody testing and had a history of upper respiratory illness consistent with COVID-19 within the 112 days prior to enrollment (Cohorts 3, 4, and 6).
- •Prior receipt of a SARS-CoV-2 vaccine other than AstraZeneca's AZD1222 (Covishield®, Vaxzevria®), JNJ-78436735, Pfizer/BioNTech (Comirnaty®), Moderna (Spikevax®), other approved or investigational adenovirus vectored vaccines, approved or investigational vaccines with a lipid nanoparticle (LNP) component, or any other approved or investigational vaccine likely to impact the interpretation of the trial data.
- •On current treatment or prevention agents with activity against SARS-CoV-
- •Participation in another research study involving receipt of an investigational product in the 60 days preceding enrollment or planned use during the study period.
- •Receipt or planned receipt of any live, attenuated vaccine within 28 days before or after study vaccination.
- •Receipt or planned receipt of any subunit or killed vaccine within 14 days before or after vaccination.
- •Administration of immunoglobulins and/or any blood products within the 3 months preceding the planned administration of first study vaccination or at any time during the study.
- •Breastfeeding, pregnant, or planning to become pregnant during the course of the study.
- •Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection with CD4+ T-cells < 400/mm3, asplenia, recurrent, severe infections and chronic (more than 14 continuous days) immunosuppressant medication within the past 6 months (inhaled, ophthalmic, and topical steroids are allowed).
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including urticaria, respiratory difficulty or abdominal pain (or any immediate allergic reaction of any severity to polysorbate due to potential cross-reactive hypersensitivity with the PEG component of the vaccine).
- •Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
- •Any history of anaphylaxis, including but not limited to reaction to vaccination.
- •History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
- •History of serious ongoing, unstable psychiatric condition that in the opinion of the investigator would interfere with study participation.
- •Bleeding disorder or prior history of significant bleeding or bruising following IM injections or venipuncture.
- •Suspected or known current alcohol abuse that in the opinion of the investigator would impede compliance with the protocol and schedules of assessments.
- •Suspected or known current alcohol abuse that in the opinion of the investigator would impede compliance with the protocol and schedules of assessments. Suspected or known drug abuse in the 5 years preceding enrollment.
- •Any other condition that in the opinion of the investigator would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results.
研究组 & 干预措施
Cohort 1: GRT-R910 10 µg, age ≥60 years (Receipt of AstraZeneca vaccine)
Healthy participants of age ≥60 years received prime dose (on Day 1) of GRT-R910 10 microgram (µg) intramuscularly at least 2 months after receiving a first-generation COVID-19 (AstraZeneca) vaccine primary series. A subset of participants elected to receive a booster vaccination of GRT-R910 10 µg which was administered 113 days after the prime vaccination. Participants not receiving booster dose were followed for 12 months, and participants receiving booster dose were followed for 16 months.
干预措施: GRT-R910 (Biological)
Cohort 2: GRT-R910 30 µg, age ≥60 years (Receipt of AstraZeneca vaccine)
Healthy participants of age ≥60 years received prime dose (on Day 1) of GRT-R910 30 µg intramuscularly at least 2 months after receiving a first-generation COVID-19 (AstraZeneca) vaccine primary series. A subset of participants elected to receive a booster vaccination of GRT-R910 10 µg, which was administered 113 days after the prime vaccination. Participants not receiving booster dose were followed for 12 months, and participants receiving booster dose were followed for 16 months.
干预措施: GRT-R910 (Biological)
Cohort 3: GRT-R910 10 µg, ≥60 years, (Receipt of AstraZeneca or Janssen COVID-19 vaccine)
Healthy participants of age ≥60 years received two doses (Day 1 and Day 29) of GRT-R910 10 µg (homologous prime-boost), at least 2 months after receiving an adenoviral COVID-19 (AstraZeneca, Janssen) primary series vaccine. Participants were followed for 13 months.
干预措施: GRT-R910 (Biological)
Cohort 4: GRT-R910 10 µg, ≥60 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine)
Healthy participants of age ≥60 years received two doses (Day 1 and Day 29) of GRT-R910 10 µg (homologous prime-boost), at least 2 months after receiving a messenger ribonucleic acid (mRNA)-based COVID-19 (Pfizer/BioNTech, Moderna) primary series vaccine. Participants were followed for 13 months.
干预措施: GRT-R910 (Biological)
Cohort 6: GRT-R910 10 µg, ≥18 to ≤59 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine)
Healthy participants of age ≥18 to ≤59 years received two doses (Day 1 and Day 29) of GRT-R910 10 µg (homologous prime-boost), at least 2 months after receiving mRNA-based COVID-19 (Pfizer/BioNTech, Moderna) primary series vaccine. Participants were followed for 13 months.
干预措施: GRT-R910 (Biological)
结局指标
主要结局
Change From Baseline in Hemoglobin at Day 8 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 8
Change From Baseline in Hemoglobin at Day 37 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 37
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 120
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 8
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 37 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 37
Change From Baseline in Bilirubin and Creatinine at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Change From Baseline in Bilirubin and Creatinine at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Change From Baseline in Bilirubin and Creatinine at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 120
Change From Baseline in Bilirubin and Creatinine at Day 8 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 8
Change From Baseline in Bilirubin and Creatinine at Day 37 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 37
Change From Baseline in Creatine Kinase at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Change From Baseline in Creatine Kinase at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Change From Baseline in Creatine Kinase at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 120
Change From Baseline in Creatine Kinase at Day 8 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 8
Change From Baseline in Creatine Kinase at Day 37 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 37
Number of Participants With Treatment-emergent Serious AEs (SAEs), AE of Special Interest (AESIs) Including Potentially Immune-mediated Medical Conditions (PIMMCs), Medically Attended AEs (MAAEs), and New Onset Chronic Medical Conditions (NOCMCs)
时间窗: Day 1 Up to 16 months
An AE or adverse experience was defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, with or without a causal relationship with the vaccine. A TEAE was defined as any event not observed before the first vaccination or any event observed before the first vaccination that worsens in intensity or frequency after exposure. A treatment-emergent SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. Adverse events of special interest were serologically or virologically confirmed SARS-CoV-2 infection or severe COVID-19, NOCMCs, MAAE (hospitalization, an emergency room visit or an otherwise unscheduled visit to or from medical personnel for any reason), and PIMMCs.
Number of Participants With at Least One Solicited Local Adverse Event (AE) Within 8 Days After the Injection of Prime Dose
时间窗: Within 8 Days After the Injection of Prime Dose on Day 1
An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. Solicited local AEs included injection site pain, injection site tenderness, injection site erythema, injection site edema/induration. Solicited AEs (reactogenicity) were collected using a memory aid.
Number of Participants With at Least One Solicited Local AE Within 8 Days After the Injection of Booster Dose
时间窗: Within 8 Days After the Injection of Booster Dose on Day 113 (Cohorts 1, 2); Within 8 Days After the Injection of Booster Dose on Day 29 (Cohorts 3, 4, 6)
An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. Solicited local AEs included injection site pain, injection site tenderness, injection site erythema, injection site edema/induration. Solicited AEs (reactogenicity) were collected using a memory aid.
Number of Participants With at Least One Solicited Systemic AE Within 8 Days After the Injection of Prime Dose
时间窗: Within 8 Days After the Injection of Prime Dose on Day 1
An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. Solicited systemic AEs included headache, fatigue, malaise, myalgia, arthralgia, nausea, fever, and chills. Solicited AEs (reactogenicity) were collected using a memory aid.
Number of Participants With at Least One Solicited Systemic AE Within 8 Days After the Injection of Booster Dose
时间窗: Within 8 Days After the Injection of Booster Dose on Day 113 (Cohorts 1, 2); Within 8 Days After the Injection of Booster Dose on Day 29 (Cohorts 3, 4, 6)
An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. Solicited systemic AEs included headache, fatigue, malaise, myalgia, arthralgia, nausea, fever, and chills. Solicited AEs (reactogenicity) were collected using a memory aid.
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Number of Participants With at Least One Unsolicited Treatment-emergent AEs (TEAEs) Within 28 Days After the Injection of Prime Dose
时间窗: Within 28 Days After the Injection of Prime Dose on Day 1
An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. A TEAE was defined as any event not observed before the first vaccination or any event observed before the first vaccination that worsens in intensity or frequency after exposure.
Number of Participants With at Least One Unsolicited TEAEs Within 28 Days After the Injection of Booster Dose
时间窗: Within 28 Days After the Injection of Booster Dose on Day 113 (Cohorts 1, 2); Within 8 Days After the Injection of Booster Dose on Day 29 (Cohorts 3, 4, 6)
An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. A TEAE was defined as any event not observed before the first vaccination or any event observed before the first vaccination that worsens in intensity or frequency after exposure.
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 120
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 8
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 37 in Cohorts 3, 4, and 6
时间窗: Baseline, Day 37
Change From Baseline in Hemoglobin at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Change From Baseline in Hemoglobin at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 8
Change From Baseline in Hemoglobin at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
时间窗: Baseline, Day 120
次要结局
- Change From Baseline in Immunoglobulin (Ig)G Level (Spike Wild Type [WT] Variant)(Baseline, Days 15, 29, 57, 58, 86, 113, 142, 180, 209, 293, 365, 394, 478)
- Change From Baseline in Neutralizing Antibody (nAb) Levels(For WT: Baseline, Days 15, 29, 57, 58, 86, 113, 142, 180, 209 293, 365, 394, 478; For Alpha, Beta, Delta, Gamma:Baseline, Days 15, 29, 57, 58, 86, 113, 142, 180, 209 293, 365, 394)
- Number of Participants With Immunogenicity Response by Spike IgG and nAb Variants(Baseline to 478 days)
- Change From Baseline in T Cell Response by Spike Pools (ex Vivo ELISpot)(Baseline, Days 8, 29, 58, 113, 142, 180, 209, 293, 365, 478)
- Change From Baseline in T Cell Response by T Cell Epitope (TCE) Pools (ex Vivo ELISpot)(Baseline, Days 8, 29, 58, 113, 142, 180, 209, 293, 365, 478)
- Change From Baseline in Immunogenicity Response by TCE Pools (in Vitro Stimulation)(Baseline, Days 8, 29, 58, 113, 142, 180, 209, 293)
- Number of Participants With Immunogenicity Response by Spike Pools and TCE Pools (ex Vivo ELISpot)(Baseline to 478 days)