Clinical trial NCT03981419: A Study to Evaluate the Effect of GRF6021 on Postoperative Recovery Following Primary Hip or Knee Arthroplasty
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postoperative Recovery
Keywords: Total hip replacement
Total knee replacement
Lead sponsor: Alkahest, Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-10
Enrollment: 38
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability and effect of GRF6021 on clinical recovery parameters in participants undergoing primary hip or knee arthroplasty.

Detailed description: 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.

Eligibility criteria: 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.
* 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.

Primary outcomes:
measure: Effect of GRF6021 on Immune Responses to Surgery as Determined by Cytometry by Time of Flight (CyTOF) on Day 2
timeFrame: Day 2 (before start of surgery and post surgery)
measure: Effect of GRF6021 on Immune Responses to Surgery as Determined by Cytometry by Time of Flight (CyTOF) on Day 3
timeFrame: Day 3
Secondary outcomes:
measure: Change in Functional Status Using the ActiGraph Wearable Device Providing Measurements for Physical Activity/Function and Sleep
timeFrame: Baseline; Day 1, Day 3 up to approximately Day 46
measure: Effects of GRF6021 on Plasma Proteomics
timeFrame: Pre-infusion on Day 1 (baseline), 2 (before start of surgery and post surgery), and Day 3
measure: 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])
timeFrame: Baseline (Day 1 pre-infusion); Days 2 (post-infusion), and 3 (pre-infusion)
measure: Time to 50% Recovery of Baseline Value on the Surgery Recovery Scale (SRS)
timeFrame: Baseline; Days 1 and 3 (pre-infusion) and thereafter up to the end of the study (approximately Day 46)
measure: End of Study (EOS) Treatment Comparison of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
timeFrame: At end of study (approximately Day 46)
measure: Time to a Score of < 12/40 on a Subset of Questions From the WOMAC, Pain Subscale
timeFrame: Days 1 and 3 (pre-infusion) and thereafter up to Day 39
measure: Time to a Score of < 18/60 on a Subset of Questions From the WOMAC, Physical Function Subscale
timeFrame: Days 1 and 3 (pre-infusion) and thereafter up to Day 39
measure: Change From Baseline in Mental Health Score in the Short Form-36 (SF-36)
timeFrame: At Baseline and end of study (approximately Day 46)
measure: Change From Baseline in Physical Health Score in the SF-36
timeFrame: At Baseline and end of study (approximately Day 46)
measure: Change From Baseline in the Beck Depression Inventory-II (BDI-II)
timeFrame: At Baseline and end of study (approximately Day 46)
measure: Number of Participants With Opioid Analgesic Consumption During Hospital Stay and After Discharge to End of Study
timeFrame: From Day 2 (post-surgery) up to end of study (approximately Day 46)
measure: Time to Discharge
timeFrame: Day 1 up to end of study (approximately Day 46)
measure: Perioperative Outcome: Surgery Duration
timeFrame: Day 2
measure: Perioperative Outcome: Duration for Which Participants Were Under Anesthesia
timeFrame: Day 2
measure: Perioperative Outcome: Duration of Stay in the Post-Anesthesia Care Unit (PACU)
timeFrame: Day 2
measure: Perioperative Outcome: Number of Participants in Each 5 American Society of Anesthesiologists (ASA) Class
timeFrame: Day 2
measure: Perioperative Outcome: Estimated Blood Loss
timeFrame: Day 2
measure: Number of Participants in Whom Intraoperative Fluids Were Administered
timeFrame: Day 2
measure: Number of Participants in Whom Intraoperative Blood Products Were Administered
timeFrame: Day 2
measure: Number of Participants Who Received Intraoperative Anesthesia
timeFrame: Day 2
measure: Number of Participants Who Received Intraoperative Opioids
timeFrame: Day 2
measure: Number of Participants With Abnormal Laboratory Blood Chemistry Values
timeFrame: At Screening and Day 3
measure: Number of Participants With Abnormal Laboratory Hematology Values
timeFrame: Day 3
measure: Number of Participants With Abnormal Laboratory Coagulation Values
timeFrame: At Screening and Day 3
measure: Number of Participants With Abnormal Laboratory Urinalysis Values
timeFrame: At Screening and Day 3
measure: Number of Participants With Abnormal Vital Signs: Blood Pressure Measurements
timeFrame: 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
measure: Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate
timeFrame: Baseline (Day 1 pre-infusion); Day 3 pre and post-infusion
measure: Change From Baseline in ECG Parameters: QT Interval and QT Interval Corrected by the Fridericia Formula (QTcF)
timeFrame: Baseline (Day 1 pre-infusion); Day 3 pre and post-infusion
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
Study officials:
affiliation: Alkahest, Inc.
name: Alkahest Medical Monitor
role: STUDY_DIRECTOR
References: