A Randomized, Placebo-Controlled, Double-Blind Pilot Study to Evaluate the Effect of GRF6021 on Intracellular Signaling Cascades in Blood Leukocytes and Postoperative Recovery Following Primary Hip or Knee Arthroplasty
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 2
- 主要终点
- Effect of GRF6021 on Immune Responses to Surgery as Determined by Cytometry by Time of Flight (CyTOF) on Day 2
研究概览
简要总结
This study will evaluate the safety, tolerability and effect of GRF6021 on clinical recovery parameters in participants undergoing primary hip or knee arthroplasty.
详细描述
This is a randomized, placebo-controlled, double-blind pilot study to investigate the effects of GRF6021, a 5% human plasma protein fraction administered by intravenous (IV) infusion, on intracellular signaling cascades in blood leukocytes in participants undergoing primary hip or knee arthroplasty.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women 50-85 years of age scheduled to undergo primary total hip or knee replacement surgery.
- •Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 .
排除标准
- •Blood coagulation disorders.
- •Participants who started chronic anticoagulant therapy (warfarin, heparin, low-molecular weight heparin, or Factor Xa inhibitors) in the last 6 months
- •Hypercoagulable state.
- •Prior hypersensitivity to any human blood product including plasma.
- •Treatment with any human blood product, including transfusions and IV immunoglobulin, during the 6 months prior to screening.
- •History of immunoglobulin A or haptoglobin deficiency.
- •Major surgery, trauma or injury in the last 3 months or minor surgery in the last 1 month.
- •Heart disease or congestive heart failure in the 6 months prior to dosing.
- •Poorly controlled hypertension.
- •Severe anemia.
- •Functional impairment of major joint or lower extremity other than joint undergoing surgery.
结局指标
主要结局
Effect of GRF6021 on Immune Responses to Surgery as Determined by Cytometry by Time of Flight (CyTOF) on Day 2
时间窗: Day 2 (before start of surgery and post surgery)
CyTOF=multiplexed, high-content immune profiling technology, providing high-resolution surveillance of circulating immune cells \& response to GRF6021 infusions on surgical recovery. Blood samples were collected for CyTOF analysis \& were stimulated with a series of extracellular ligands to analyze evoked intracellular signaling responses. High-dimensional data results were obtained from CytOF, and analyzed using the immunological elastic net (iEN) algorithm, a penalized regression method particularly adapted for the analysis of highly correlated data, as it eliminates redundant parameters while retaining interrelated parameters. Raw data obtained from each sample was entered into the classification model (iEN algorithm) that generated prediction values (presented below) showing the effect of study treatment on immune response post-surgery. A prediction value of 0 \& 1 indicated perfect results (i.e., positive response to treatment) for the placebo \& GRF6021 arms, respectively.
Effect of GRF6021 on Immune Responses to Surgery as Determined by Cytometry by Time of Flight (CyTOF) on Day 3
时间窗: Day 3
CyTOF=multiplexed, high-content immune profiling technology, providing high-resolution surveillance of circulating immune cells \& response to GRF6021 infusions on surgical recovery. Blood samples were collected for CyTOF analysis \& were stimulated with a series of extracellular ligands to analyze evoked intracellular signaling responses. High-dimensional data results were obtained from CytOF, and analyzed using the immunological elastic net (iEN) algorithm, a penalized regression method particularly adapted for the analysis of highly correlated data, as it eliminates redundant parameters while retaining interrelated parameters. Raw data obtained from each sample was entered into the classification model (iEN algorithm) that generated prediction values (presented below) showing the effect of study treatment on immune response post-surgery. A prediction value of 0 \& 1 indicated perfect results (i.e., positive response to treatment) for the placebo \& GRF6021 arms, respectively.
次要结局
- End of Study (EOS) Treatment Comparison of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)(At end of study (approximately Day 46))
- Change in Functional Status Using the ActiGraph Wearable Device Providing Measurements for Physical Activity/Function and Sleep(Baseline; Day 1, Day 3 up to approximately Day 46)
- Effects of GRF6021 on Plasma Proteomics(Pre-infusion on Day 1 (baseline), 2 (before start of surgery and post surgery), and Day 3)
- Number of Participants With Change From Baseline in Delirium as Assessed Using 3-Minute Diagnostic Interview for Confusion Assessment Method (3-Minute Diagnostic Interview for Confusion [3D-CAM])(Baseline (Day 1 pre-infusion); Days 2 (post-infusion), and 3 (pre-infusion))
- Time to 50% Recovery of Baseline Value on the Surgery Recovery Scale (SRS)(Baseline; Days 1 and 3 (pre-infusion) and thereafter up to the end of the study (approximately Day 46))
- Number of Participants in Whom Intraoperative Fluids Were Administered(Day 2)
- Number of Participants in Whom Intraoperative Blood Products Were Administered(Day 2)
- Number of Participants Who Received Intraoperative Opioids(Day 2)
- Time to a Score of < 12/40 on a Subset of Questions From the WOMAC, Pain Subscale(Days 1 and 3 (pre-infusion) and thereafter up to Day 39)
- Time to a Score of < 18/60 on a Subset of Questions From the WOMAC, Physical Function Subscale(Days 1 and 3 (pre-infusion) and thereafter up to Day 39)
- Change From Baseline in the Beck Depression Inventory-II (BDI-II)(At Baseline and end of study (approximately Day 46))
- Time to Discharge(Day 1 up to end of study (approximately Day 46))
- Perioperative Outcome: Surgery Duration(Day 2)
- Number of Participants With Abnormal Laboratory Blood Chemistry Values(At Screening and Day 3)
- Change From Baseline in Mental Health Score in the Short Form-36 (SF-36)(At Baseline and end of study (approximately Day 46))
- Change From Baseline in Physical Health Score in the SF-36(At Baseline and end of study (approximately Day 46))
- Number of Participants With Opioid Analgesic Consumption During Hospital Stay and After Discharge to End of Study(From Day 2 (post-surgery) up to end of study (approximately Day 46))
- Perioperative Outcome: Duration for Which Participants Were Under Anesthesia(Day 2)
- Perioperative Outcome: Estimated Blood Loss(Day 2)
- Number of Participants With Abnormal Laboratory Coagulation Values(At Screening and Day 3)
- Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate(Baseline (Day 1 pre-infusion); Day 3 pre and post-infusion)
- Perioperative Outcome: Duration of Stay in the Post-Anesthesia Care Unit (PACU)(Day 2)
- Perioperative Outcome: Number of Participants in Each 5 American Society of Anesthesiologists (ASA) Class(Day 2)
- Number of Participants Who Received Intraoperative Anesthesia(Day 2)
- Number of Participants With Abnormal Laboratory Hematology Values(Day 3)
- Number of Participants With Abnormal Laboratory Urinalysis Values(At Screening and Day 3)
- Number of Participants With Abnormal Vital Signs: Blood Pressure Measurements(Pre-infusion at Days 1, 2 (Pre and Postoperative) and 3; At Post infusion on Day 1 (15, 30, 45, 60 mins); Day 2 Preoperative (15, 30, 45 mins); Postoperative (30 mins); Day 3 (15 and 30 mins); and 30 mins after end of each infusion)
- Change From Baseline in ECG Parameters: QT Interval and QT Interval Corrected by the Fridericia Formula (QTcF)(Baseline (Day 1 pre-infusion); Day 3 pre and post-infusion)