A Randomized, Placebo-Controlled, Phase 2 Study of HB-101, a Bivalent Cytomegalovirus (CMV) Vaccine, in CMV-Seronegative Recipient (R-) Patients Awaiting Kidney Transplantation From Living CMV-Seropositive Donors (D+).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 50
- 主要终点
- Number of Participants With Adverse Events and Serious Adverse Events
研究概览
简要总结
HB-101 is a bivalent recombinant vaccine against human CMV infection. This is a randomized, placebo-controlled, phase 2 study to assess the safety, reactogenicity, immunogenicity, and efficacy of HB-101 in CMV-Seronegative patients receiving a kidney transplant from a CMV-Seropositive living donor and CMV-Seropositive patients.Patients enrolled should have a living donor kidney transplantation ideally planned between two to four months after the first injection of study drug (HB-101 or placebo).
详细描述
This is a randomized, placebo-controlled, phase 2 study to assess the safety, reactogenicity, immunogenicity, and efficacy of HB-101 in adult patients awaiting kidney transplantation. For Groups 1 and 2, adult CMV-seronegative (-) patients awaiting kidney transplant from a CMV-seropositive (+) living donor will be enrolled according to treatment intent with regard to the method of CMV prevention after transplant (either preemptive or prophylactic). This will be defined at study enrollment by the investigator and institutional standards. Patients enrolled in Group 1 and 2 will be randomized to receive HB-101 or placebo. For Group 3, adult CMV-seropositive (+) patients awaiting kidney transplant from either CMV-seropositive(+) or CMV-seronegative(-) living donors will be enrolled. Group 3 will be open label where all patients will receive HB-101. The post transplant management for Group 3 patients will also follow either preemptive or prophylactic method per the institution standards. The intent of the study is to administer three doses of the study drug (HB-101 or placebo) prior to transplantation and within proximity to the time of transplantation. However, two doses of study drug will be sufficient for the patients to be included in the efficacy analyses if a third dose of study drug is not feasible due to transplantation timelines. Patients will not receive study drug after transplantation. Patients will be recruited globally from transplant centers. The total duration of the study of each patient participating in the study will be approximately 15 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The participants, investigators and care providers (study site personnel) will be blinded.
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who meet all of the following key inclusion criteria will be eligible to participate in the study:
- •Male or female patients 18 years of age or older.
- •Patients must be eligible to undergo kidney transplantation from a living donor as per institutional standards.
- •For Groups 1 and 2 only: Patients must be CMV immunoglobulin G (IgG) seronegative (-) and receiving kidney for transplantation from donors who are CMV IgG seropositive (+).
- •For Group 3 only: Patients must be CMV immunoglobulin G (IgG) seropositive (+) and receiving kidney for transplantation from donors who are either CMV IgG seronegative (-) or seropositive (+).
- •Patients who would comply with the requirements of this protocol (e.g., return for follow up visits), as judged by the investigator.
排除标准
- •Patients who meet any of the following key criteria will be excluded from the study:
- •Patients planning to undergo multi-organ transplantation.
- •Patients participating in another interventional clinical study.
- •Previous vaccination with an investigational CMV vaccine.
- •Any confirmed or suspected immunodeficiency disorder (based on medical history and physical examination) that could interfere with the immune response or that presents a risk for the patient to receive a vaccine candidate in development.
- •Treatment with any chronic immunosuppressive medication or other immuno modifying drugs within 6 months prior to study entry. However, inhaled and topical steroids and low-dose oral corticosteroids (<10 milligrams a day of prednisone or equivalent) are allowed.
- •Prior history of CMV disease or CMV infection requiring anti-viral therapy
- •Patients with a rash, dermatological condition, or tattoo in the area of the injection site(s) that could interfere with administration site reaction rating. (Note: The injection site(s) can be the non-dominant arm [most preferred injection site], dominant arm, or either thigh [least preferred injection site], as judged by the investigator).
- •It is anticipated that the patient will be unavailable to complete the study follow-up.
- •Patients who are highly sensitized or who are likely to undergo desensitization at time of transplant (e.g., donor-specific antibody titers at the local laboratory >2000).
结局指标
主要结局
Number of Participants With Adverse Events and Serious Adverse Events
时间窗: 15 Months
Assess the number and severity of participants with adverse events and serious adverse events
Assessment of Humoral Immunogenicity Analyses
时间窗: 15 Months
Assessment of CMV neutralizing antibody titers (NTAs) at day of Transplant defined by log10 virus neutralising unit(s)
Change of Oral Body Temperature.
时间窗: Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months
Oral body temperature was measured in degrees Celsius prior to study drug administrations and seven days after. The results express the change from baseline (defined as the last measurement prior to the first dose of study drug) to Dose 3.
Assessment of Cellular Immunogenicity Analyses
时间窗: 15 months
Assessment of positive CMV IFNγ ELISPOT results for pp65 and gB defined by Spot forming cells / mio PBMC per CMV Management Strategy and Doses Before Transplant
Number of Patients With Injection Site Events.
时间窗: 15 Months
Number of patients experiencing a local or generalized injection site reaction
Change of Respiration Rate.
时间窗: Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months.
Respiration rate in breaths per minute was measured prior to study drug administration and seven days after. The results express the change from baseline (defined as the last measurement prior to the first dose of study drug) to Dose 3.
Change of Blood Pressure.
时间窗: Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months
Diastolic and Systolic Blood Pressure was measured in millimeters of mercury (mmHg) prior to study drug administration and seven days after. The results express the change from baseline (defined as the last measurement prior to the first dose of study drug) to Dose 3.
次要结局
- Time to Clinically Significant CMV Infection.(12 months)
- Number of Participants With CMV Viremia Requiring Anti Viral Therapy(12 months)
- Time to Organ Rejection(Up to 12 months post transplantation)
- The Duration of Anti-CMV Therapy Courses Required.(12 months)
- The Time to CMV Viremia Requiring Anti Viral Therapy.(12 months)
- Number of Participants Requiring Anti-CMV Therapy(12 months)
- Number of Participants With Organ Rejection(Up to 12 months post transplantation)