A Study to Evaluate the Effect of GRF6021 on Postoperative Recovery Following Primary Hip or Knee Arthroplasty

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability and effect of GRF6021 on clinical recovery parameters in patients undergoing primary hip or knee arthroplasty.

Detailed Description
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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 subjects undergoing primary hip or knee arthroplasty.

Official Title
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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

Conditions
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Postoperative Recovery

Intervention / Treatment
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* Biological: GRF6021
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 . Exclusion Criteria: Blood coagulation disorders. Subjects 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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GRF6021<br>Subjects will receive GRF6021 per the following schedule: On the day before surgery On the day of surgery within 4 hours before surgery start (first incision) On the day of surgery upon arrival in the postoperative care unit (within 5 hours after the first incision) On the day after surgery | Biological: GRF6021<br>* for IV infusion<br>|
| Placebo Comparator: Placebo<br>Subjects will receive Placebo per the following schedule: On the day before surgery On the day of surgery within 4 hours before surgery start (first incision) On the day of surgery upon arrival in the postoperative care unit (within 5 hours after the first incision) On the day after surgery | Other: Placebo<br>* for IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracellular signaling cascades in blood leukocytes | Effect of GRF6021 on intracellular signaling cascades in blood leukocytes as determined by CyTOF. | Baseline to Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) | Change from baseline in 3D-CAM. The 3D-CAM is a verbal assessment tool used to test patients for delirium. Each item in the instrument directly informs acute onset of mental status change or fluctuating course of cognition, inattention, disorganized thinking, and altered level of consciousness. | Baseline to Day 3 | 
| Surgery Recovery Scale (SRS) | Time to 50% recovery of the baseline value in the SRS. The SRS tool assesses functional recovery following major surgery. Impacts on daily activities are scored from 1 to 5 or 6 (1= not at all). | Baseline to 6 weeks | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Pain] | Time to a score of < 12/40 on a subset of questions from the WOMAC, Pain Subscale. The WOMAC assesses pain, stiffness, and physical function in patients with knee and/or hip osteoarthritis. This is an 11-point scale (0-10). The range for the Pain subscale is 0-40 . The subscales are used independently and not summed. Higher scores = worse (Higher pain score = more pain; higher function score = more impairment) | Baseline to 6 weeks | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Function] | Time to a score of < 18/60 on a subset of questions from the WOMAC, Physical Function Subscale. The WOMAC assesses pain, stiffness, and physical function in patients with knee and/or hip osteoarthritis. This is an 11-point scale (0-10). The range for the Function subscale is 0-60 . The subscales are used independently and not summed. Higher scores = worse (Higher pain score = more pain; higher function score = more impairment) | Baseline to 6 weeks | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Total] | The WOMAC total is a sum of scores from the Pain, Stiffness and Function Subscales. The WOMAC assesses pain, stiffness, and physical function in patients with knee and/or hip osteoarthritis. This is an 11-point scale (0-10). The range for the combined subscales is 0-240. (Higher total score = more pain, stiffness, and impairment) | Baseline to 6 weeks | 
| Short Form Health Survey 36 (SF-36) | Change from baseline in the SF-36. The SF-36 is a health-related quality-of-life measure, using 8 sub-scale scores and 2 summary scores for mental and physical health. Range: 0-100 Lower = worse Eight subscales vitality physical functioning bodily pain general health perceptions physical role functioning emotional role functioning social role functioning mental health Subscales scores are converted to a z score and given equal weight; max total score is 100 | Baseline to 6 weeks | 
| Beck Depression Inventory-II (BDI-II) | Change from baseline in the BDI-II. The BDI-II assesses mood in a 21-item self-administered survey. It is scored on a scale of 0-63 in a list of four statements arranged in increasing severity about a particular symptom of depression. Range 0-63 Higher = worse Subscales N/A | Baseline to 6 weeks | 
| Opioid Analgesic Consumption | Opioid analgesic consumption during hospital stay and after discharge to end of study. | Baseline to 6 weeks | 
| Discharge | Time to discharge. | Baseline to 6 weeks | 
| Perioperative outcomes [Blood] | Intraoperative blood products (mL) | Baseline to Day 2 | 
| Perioperative outcomes [Fluids] | Intraoperative fluids (mL) | Baseline to Day 2 | 
| Functional status using the ActiGraph | Change in functional status using the ActiGraph wearable device providing measurements for physical activity, mobility, and sleep. | Baseline to 6 weeks | 
| Vital sign measurements [BP] | Change from baseline in vital sign measurements: Blood pressure (mm Hg) | Baseline to Day 3 | 
| Vital sign measurements [Heart] | Change from baseline in vital sign measurements: Heart rate (bpm) | Baseline to Day 3 | 
| Electrocardiogram (ECG) [Rate] | Change from baseline in ECG: Rate (bpm) | Baseline to Day 3 | 
| Electrocardiogram (ECG) [Rhythm] | Change from baseline in ECG: Rhythm (sinus or non-sinus) | Baseline to Day 3 | 
| Electrocardiogram (ECG) [QT] | Change from baseline in ECG: QT interval (ms) | Baseline to Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Total hip replacement, Total knee replacement