A Phase 1B Double Blinded Randomized Trial Evaluating Safety, Tolerability, and Immune Response of OSU-2131 a BZLF1 Peptide Vaccine With Stimulon™ QS-21 Solution Adjuvant in Healthy Volunteers and Patients Awaiting Solid Organ Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events
研究概览
简要总结
This phase 1B trial tests the safety, side effects and best dose of rh-Hsc70- BZLF1 peptide complex (OSU-2131) with Stimulon (Trademark) QS-21 and evaluates how well it works in preventing Epstein-Barr virus (EBV) infection and related cancers in healthy volunteers and patients awaiting a solid organ transplant. Currently, patients who receive an organ transplant receive immune suppression therapy which can make it harder for the body to fight infections. This treatment also increases the risk for cancers that are triggered by the EBV. Vaccines made from synthetic peptide (RAKFKQLL) derived from the BZLF1 protein, may help the body build an effective immune response against EBV infections. QS-21, a saponin adjuvant, is a substance from plants that, when given with vaccine therapy, may improve the way the immune system responds to disease. Giving OSU-2131 with QS-21 may help the immune system fight EBV and protect against EBV infection and the cancers that it can cause in patients awaiting solid organ transplants.
详细描述
PRIMARY OBJECTIVE:
I. Determine the overall safety profile of three different dose levels of OSU-2131 vaccination each with 50 mcg Stimulon (Trademark) Quillaja saponin (QS)-21 Solution adjuvant (QS-21), wherein the OSU-2131 doses are 80, 240 and 480 mcg in healthy volunteers and similar safety profile of the identified maximum tolerated dose (MTD) in patients awaiting solid organ transplantation.
SECONDARY OBJECTIVES:
I. Determine the optimal immunologic dose (OID) to OSU-2131 vaccination (with QS-21) in all dose cohorts of 80, 240, and 480 mcg OSU-2131 (healthy volunteers) and, upon completing safety assessment, patients awaiting solid organ transplant (PASOT).
II. To perform laboratory correlative studies to examine immune responses to the OSU-2131 vaccine with the intent to communicate the research results and to generate a de-identified data set that can then be used for future comparisons with immune response data generated in future vaccine trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Healthy volunteers, patients, and site staff evaluating the patients will be blinded to treatment assignment.
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 volunteers and patients awaiting solid organ transplantation (SOT) must have at least one allele for HLA-B*08:01
- •Subjects can be Epstein-Barr virus (EBV) seronegative or seropositive
- •Subjects must be seronegative for HIV
- •Subjects must be seronegative for hepatitis B and C
- •Have baseline chemistry and hematology (hemoglobin, white blood cells, absolute neutrophil count, eosinophils) within normal limits
- •Prothrombin time (PT) and partial thromboplastin time (PTT) below the upper limit of normal
- •Platelets above the lower limit of normal (LLN)
- •Basophils, lymphocytes, and monocytes must be within 1.2 x upper limit of normal (ULN) or 0.8 x LLN and considered not clinically significant by the investigator
- •Total creatine kinase (CK) laboratory values < 1.25 x the upper limit of normal (according to the normal reference ranges of the Ohio State University [OSU] laboratory) at baseline (screening & pre-study visit) and considered not clinically significant by the investigator
- •Subjects must not be taking antiviral therapy
- •Must be ≥ 18 years of age and ≤ 65 years of age and willing to either use an effective method of contraception or abstain from sexual activity for at least 3 months following the last dose of vaccination
- •Female of childbearing potential must have a negative serum pregnancy test prior to the first study drug/placebo (PBS) administration
- •Agree not to receive any other investigational drug while enrolled in this study
- •Provide written informed consent according to International Conference on Harmonization-Good Clinical Practice (ICH-GCP) and local regulations
- •Following successful completion of safety evaluation for the phase 1 dose escalation phase of this trial in healthy volunteers and review of this data by the Sponsor and Food and Drug Administration (FDA), we plan to enroll a second cohort of patients awaiting solid organ transplantation (SOT). We will recruit patients with end stage renal disease (ESRD) who are awaiting kidney transplantation. ESRD is defined according to 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for the Evaluation and Management of Chronic Kidney Disease (Acosta-Ochoa et al, J Clin Med, 8(9):1323, 2019). KDIGO defines ESRD as: stage 4: severe reduction in glomerular filtration rate (GFR) (15 to 29 mL/min); stage 5: renal failure (GFR less than 15 mL/min). Patients will qualify for ESRD / kidney transplantation per need for maintenance dialysis due to one or more of the criteria related to renal insufficiency: volume overload, metabolic acidosis, electrolyte disturbance, drug toxicity, etc. Patients will be regularly undergoing hemodialysis or peritoneal dialysis for metabolic support. Patients will be excluded from the study if they have any unstable medical conditions which the investigator believes would preclude participation in the study. These conditions include but are not limited to cardiorenal and hepatorenal syndromes
排除标准
- •Severe active infection, compromised cardiopulmonary function, or other serious medical illness that, in the opinion of the principal investigator, would prevent study completion
- •History of chronic active EBV infection, active infectious mononucleosis (or infectious mononucleosis within 6 months of enrollment), or other EBV-related disorder as determined by principal investigator (PI)
- •History of immune suppression or autoimmune disorder
- •Concomitant use of systemic corticosteroids or other immunosuppressive medications (including nasal and inhaled steroids). The use of nasal steroids for seasonal rhinitis is acceptable
- •Pregnant or breastfeeding subjects
- •For patient enrollment on the second cohort, "patients awaiting SOT", we will consider patients awaiting kidney transplantation who are receiving maintenance renal replacement therapy (dialysis). Most patients on routine renal replacement therapy (dialysis) will present with stable chemistry, acid base balance, volume status and clear mental status. For patients who are non-compliant with routine dialysis, laboratory abnormalities and acid base, volume status can become abnormal. Specific dose limiting toxicity (DLT) criteria that may relate to patients with ESRD include laboratory parameters that may altered due to missed dialysis session(s). Most laboratory abnormalities in such patients can be corrected by restarting dialysis or blood transfusions. Outside these specific variables, we do not expect to see specific DLT criteria for patients with ESRD on this study. Metabolic derangement such as acid base imbalance, hyperkalemia and volume overload as a result of missing dialysis session. Study stopping rule for subjects awaiting organ transplant: Occurrence of this event in two or more subjects should result in study pause. Patients who are unable to adhere to routine dialysis will be excluded from the study if they have any unstable medical conditions which the investigator believes would preclude participation in the study. These conditions include but are not limited to cardiorenal and hepatorenal syndromes
研究组 & 干预措施
Group I (OSU-2131, QS-21)
Healthy volunteers and patients receive OSU-2131 SC with QS-21 SC on day 0, and weeks 2 and 4 in the absence of unacceptable toxicity or patient proceeds to transplant. Healthy volunteers and patients additionally undergo blood sample collection throughout the study.
干预措施: QS21 (Biological)
Group I (OSU-2131, QS-21)
Healthy volunteers and patients receive OSU-2131 SC with QS-21 SC on day 0, and weeks 2 and 4 in the absence of unacceptable toxicity or patient proceeds to transplant. Healthy volunteers and patients additionally undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Group II (placebo)
Healthy volunteers receive PBS SC on day 0, and weeks 2 and 4 in the absence of unacceptable toxicity. Healthy volunteers additionally undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Group II (placebo)
Healthy volunteers receive PBS SC on day 0, and weeks 2 and 4 in the absence of unacceptable toxicity. Healthy volunteers additionally undergo blood sample collection throughout the study.
干预措施: Dulbecco''s Phosphate-Buffered Saline (Drug)
Group I (OSU-2131, QS-21)
Healthy volunteers and patients receive OSU-2131 SC with QS-21 SC on day 0, and weeks 2 and 4 in the absence of unacceptable toxicity or patient proceeds to transplant. Healthy volunteers and patients additionally undergo blood sample collection throughout the study.
干预措施: Peptide Vaccine (Biological)
结局指标
主要结局
Incidence of treatment-emergent adverse events
时间窗: From the first administration of treatment until the week 28 visit
Will be coded to body systems and preferred terms using the Medical Dictionary for Regulatory Activities. Descriptive statistics, per treatment arm, will contain the number and percentage of subjects who experience at least one adverse event (AE), AE related to study treatment, serious AE, serious AE related to study treatment, grade 3 or 4 AE, and grade 3 or 4 related to study treatment. The number and percentage of subjects who discontinue treatment due to an AE will be provided, together with the number and percentage of subjects who die due to an AE.
Changes in laboratory parameters and vital signs
时间窗: At baseline and up to week 56
Changes will be summarized for subjects in each treatment arm. Baseline laboratory values will be summarized. The number and percentage of subjects with values below, within, and above normal range for each lab parameter will be summarized. Clinically significant abnormalities noted by the clinician during laboratory evaluations will be summarized by treatment arm.
Pre- and post-injection vital signs
时间窗: Up to week 4
The number and percent of subjects who experience a clinically significant change in vitals from pre-injection to post-injection will be tabulated and summarized by treatment arm.
Injection site reactions
时间窗: At 10 and/or 60 minutes post injection on weeks 0, 2 and 4
The number and percent of subjects who experience induration at 10 minutes post injection and/or 60 minutes post injection will be tabulated and summarized by treatment arm. The number and percent of subjects who experience erythema at 10 minutes post injection and/or 60 minutes post injection will be tabulated and summarized by treatment arm.
次要结局
- Immune response(At baseline, day 0, and weeks 2, 4, 6, 12, 28, 40, and 56)
- Optimal immunologic dose (OID)(Up to week 12)
研究者
Timothy Voorhees
Principal Investigator
Ohio State University Comprehensive Cancer Center