A Randomized, Open-label Study to Evaluate the Immunogenicity of Anthrax Vaccine Adsorbed Alone or Concomitantly With Raxibacumab (GSK3068483)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 573
- 试验地点
- 1
- 主要终点
- Ratio of Geometric Mean Concentrations (GMC) of Anti-protective Antigen (PA) Antibody (Ab) at 4 Weeks (Day 29) After the First AVA Dose (Prior to the Third AVA Dose), Between the AVA Alone and the AVA With Raxibacumab Treatment Groups
研究概览
简要总结
This study, as a post-marketing commitment to the Food and Drug Administration, is designed to detect the effect of raxibacumab on anthrax vaccine adsorbed (AVA) immunogenicity in a healthy volunteer population. This is a randomized, open-label, parallel group, two arm study to compare the immunogenicity of AVA at 4 weeks after the first AVA dose, when AVA is administered alone or concomitantly with raxibacumab. The study is planned to enroll approximately 30 to 534 subjects in up to 3 cohorts. The total duration of the study will be approximately 26 weeks. The dates reflect cohort 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination and laboratory tests
- •Men and women between 18 to 65 years of age
- •Willing and able to adhere to the procedures stated in the protocol.
- •Female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:
- •Non-reproductive potential defined as:
- •Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
- •Reproductive potential and agrees to follow one of the options listed in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP), from 30 days prior to the first dose of study medication and until after the last dose of study medication and completion of the follow-up visit at Day 183 (at least five terminal half-lives for raxibacumab).
排除标准
- •Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or non-investigational study vaccine/product (pharmaceutical product or device).
- •Be a member of the military, a laboratory worker, first responder, health care worker, or otherwise be at higher risk of exposure to anthrax.
- •History of regular alcohol consumption within 1 month of the study defined as:
- •An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- •Female planning to become pregnant or planning to discontinue contraceptive precautions before the Day 183 study visit.
- •Pregnant (confirmed by a serum or urine hCG test) or lactating female.
- •Alanine aminotransferase (ALT) and bilirubin >1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders).
- •Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test results at screening or within 3 months prior to first dose of study treatment.
- •A positive pre-study drug/alcohol screen.
- •A positive test for HIV antibody.
- •History of sensitivity to any of the study medications, or components thereof (especially latex and aluminium) or a history of other known drug allergies that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation.
- •Have previously been vaccinated against PA.
- •Have an anti-PA Ab concentration >2 times the lower limit of quantitation at screening.
- •Administration of immunoglobulins not included in this trial and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
- •Administration of long-acting immune-modifying drugs (e.g. infliximab) within six months prior to the first vaccine dose or expected administration at any time during the study period.
- •Chronic administration (defined as more than 14 consecutive days) of systemic immunosupressants or other immune-modifying drugs within six months prior to the first vaccine dose. Inhaled, topical and intra-articular corticosteroids are allowed.
- •Administration or planned administration of a vaccine not foreseen by the study protocol within the period starting 35 days before the first dose of study vaccine(s) and ending 30 days after the last dose of study vaccine. This includes any type of vaccine such as (but not limited to) live, inactivated, and subunit vaccines. Influenza vaccines are permitted after Week
- •Subjects must abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study.
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- •Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.
研究组 & 干预措施
Anthrax Vaccine Adsorbed
Subjects will be administered subcutaneous (SC) 0.5 mL AVA doses on Days 1, 15, and 29 (0, 2, and 4 weeks).
干预措施: AVA (Biological)
AVA + Raxibacumab
Subjects will be administered SC 0.5 mL AVA doses on Days 1, 15, and 29 (0, 2, and 4 weeks), with the first AVA dose administered immediately after completion of a single intravenous (IV) infusion 40 milligram (mg)/kilogram (kg) raxibacumab dose. Subjects will be premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions.
干预措施: AVA (Biological)
AVA + Raxibacumab
Subjects will be administered SC 0.5 mL AVA doses on Days 1, 15, and 29 (0, 2, and 4 weeks), with the first AVA dose administered immediately after completion of a single intravenous (IV) infusion 40 milligram (mg)/kilogram (kg) raxibacumab dose. Subjects will be premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions.
干预措施: Raxibacumab (Biological)
AVA + Raxibacumab
Subjects will be administered SC 0.5 mL AVA doses on Days 1, 15, and 29 (0, 2, and 4 weeks), with the first AVA dose administered immediately after completion of a single intravenous (IV) infusion 40 milligram (mg)/kilogram (kg) raxibacumab dose. Subjects will be premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions.
干预措施: Diphenhydramine (Drug)
结局指标
主要结局
Ratio of Geometric Mean Concentrations (GMC) of Anti-protective Antigen (PA) Antibody (Ab) at 4 Weeks (Day 29) After the First AVA Dose (Prior to the Third AVA Dose), Between the AVA Alone and the AVA With Raxibacumab Treatment Groups
时间窗: Day 29
Ratio of the GMC of anti-PA Ab between AVA alone and the AVA with raxibacumab treatment group was assessed to compare the immunogenicity of AVA at 4 weeks after the first AVA dose (prior to the third AVA dose). Serum AVA derived anti-PA Ab concentrations were determined using an approved immunoassay. Per Protocol (PP) population was used in analysis which comprised of all analyzable participants (those who received at least the Week 0 \[Day 1\] and Week 2 \[Day 15\] AVA doses within the protocol specified visit window; receive the raxibacumab dose, if randomized to Treatment Group 2 and; completed the primary study endpoint assessment \[anti-PA Ab concentration at Week 4\]).
次要结局
- Change From Baseline in Heart Rate at Indicated Time Points(Baseline and up to Day 183)
- Number of Participants With Hematology Parameters Outside Normal Range(Up to Day 57)
- Ratio of GMC of Anti-PA Ab at Weeks 8 and 26 (Days 57 and 183) After the First AVA Dose, Between the AVA Alone and AVA With Raxibacumab Treatment Groups(Days 57 and 183)
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points(Baseline and up to Day 183)
- Change From Baseline in Respiratory Rate at Indicated Time Points(Baseline and up to Day 183)
- Number of Participants With Clinical Chemistry Parameters Outside Normal Range(Up to Day 57)
- Number of Participants With Urinalysis Parameters(Day 57)
- Percentage of Participants Who Seroconvert, at Weeks 4, 8, and 26 (Days 29, 57 and 183) After the First AVA Dose, Between the AVA Alone and the AVA With Raxibacumab Treatment Groups(Days 29, 57 and 183)
- Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (AE)(Up to Day 183)
- Change From Baseline in Temperature at Indicated Time Points(Baseline and up to Day 183)