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

NCT03981419 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AKST6021-211
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Recovery

Keywords

Total hip replacement; Total knee replacement

Outcome Measures

Primary Outcomes (2)

• Effect of GRF6021 on Immune Responses to Surgery as Determined by Cytometry by Time of Flight (CyTOF) on Day 2

  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.

  Day 2 (before start of surgery and post surgery)

• Effect of GRF6021 on Immune Responses to Surgery as Determined by Cytometry by Time of Flight (CyTOF) on 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.

  Day 3

Secondary Outcomes (28)

• 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)

• End of Study (EOS) Treatment Comparison of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)

  At end of study (approximately Day 46)

Study Arms (2)

GRF6021

EXPERIMENTAL

Participants received 4 doses of GRF6021, 250 milliliters (mL), intravenous (IV) infusion. The first dose was administered on day before surgery, the next two doses on the day of surgery i.e., within 4 hours before start of surgery (first incision), and then upon arrival in the postoperative care unit (within 5 hours after the first incision) and the last dose was administered on the day after the surgery.

Biological: GRF6021

Placebo

PLACEBO COMPARATOR

Participants received 4 doses of GRF6021 matching placebo, 250 mL, IV infusion. The first dose was administered on day before surgery, the next two doses on the day of surgery i.e., within 4 hours before start of surgery (first incision), and then upon arrival in the postoperative care unit (within 5 hours after the first incision) and the last dose was administered on the day after the surgery.

Other: Placebo

Interventions

GRF6021 BIOLOGICAL

for IV infusion

GRF6021

Placebo OTHER

for IV infusion

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 .

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alkahest, Inc.: lead

Study Sites (1)

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

Related Publications (1)

• Gaudilliere B, Xue L, Tsai AS, Gao X, McAllister TN, Tingle M, Porras G, Feinstein I, Feyaerts D, Verdonk F, Sabayev M, Hedou J, Ganio EA, Berson E, Becker M, Espinosa C, Kim Y, Lehallier B, Rawner E, Feng C, Amanatullah DF, Huddleston JI, Goodman SB, Aghaeepour N, Angst MS. Infusion of young donor plasma components in older patients modifies the immune and inflammatory response to surgical tissue injury: a randomized clinical trial. J Transl Med. 2025 Feb 14;23(1):183. doi: 10.1186/s12967-025-06215-w.

  PMID: 39953524 DERIVED

Results Point of Contact

• Title: Head of Communications
• Organization: Alkahest, Inc.

info@alkahest.com

(650) 801-0474

Study Officials

• Alkahest Medical Monitor

  Alkahest, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: June 10, 2019
• Study Start: July 12, 2019
• Primary Completion: January 23, 2021
• Study Completion: March 4, 2021
• Last Updated: March 13, 2024
• Results First Posted: March 13, 2024

Record last verified: 2024-02

Locations

US (1)