Saline-Controlled Study of nSTRIDE APS for Knee Osteoarthritis (PROGRESS IV)

A Multicenter, Double-Blind, Randomized, Saline-Controlled Study of a Single, Intra-articular Injection of Autologous Protein Solution in Patients With Knee Osteoarthritis

A double-blind, multicenter, randomized, controlled trial (RCT) that will evaluate the efficacy of a single dose of Autologous Protein Solution (APS) in patients with Osteoarthritis (OA) of the knee.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Device: nSTRIDE APS; Device: Saline

Detailed Description

A double-blind, multicenter, randomized, saline-controlled trial (RCT) that will evaluate the efficacy of a single dose of Autologous Protein Solution (APS) in patients with symptomatic osteoarthritis (OA) of the knee who have not been able to get satisfactory pain relief with prior treatment.

• Study Type: Interventional
• Enrollment (Actual): 332
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University Of Alabama
    • Guntersville, Alabama, United States, 35976
      • Avant Research Associates, LLC
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Tucson Orthopaedic Institute, PC
  • California
    • Encinitas, California, United States, 92024
      • CORE Orthopaedic Medical Center
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Andrews Research and Education Foundation (AREF)
    • Orlando, Florida, United States, 32804
      • Florida Hospital Orthopaedic Institute and Fracture Care Center
    • West Palm Beach, Florida, United States, 33409
      • Comprehensive Clinical Trials, Llc
  • Illinois
    • Rockford, Illinois, United States, 61114
      • Orthoillinois, Ltd.
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Orthopedic & Sports Medicine Center
    • Greenwood, Indiana, United States, 46143
      • OrthoIndy
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center Research Institute, Inc.
  • Massachusetts
    • Foxboro, Massachusetts, United States, 02035
      • Brigham and Women's Mass General Health Care Center
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health - Great Neck
    • New York, New York, United States, 10065
      • Northwell Health - Lenox Hill
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • University of Cincinnati College of Medicine
    • Columbus, Ohio, United States, 43221
      • Ohio State University
    • New Albany, Ohio, United States, 43054
      • Joint Implant Surgeons, Inc
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Campbell Foundation
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Plano, Texas, United States, 75093
      • Texas Center for Joint Replacement
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Richmond, Virginia, United States, 23294
      • OrthoVirginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female ≥ 21 and ≤ 80 years old at the time of screening
• Willingness and ability to comply with the study procedures and visit schedules and ability to follow oral and written instructions
• A standing radiograph of the knee showing a Kellgren-Lawrence grade of 2 to 4 and an absence of severe osteoarthritis
• Body Mass Index ≤ 40
• A qualifying WOMAC LK 3.1 pain subscale total score
• Has undergone at least one prior conservative osteoarthritis treatment
• Signed an institutional review board approved informed consent

Exclusion Criteria:

• Presence of clinically observed active infection in the index knee
• Presence of symptomatic osteoarthritis in the non-study knee
• Diagnosed with rheumatoid arthritis, Reiter's syndrome, psoriatic arthritis, gout, ankylosing spondylitis, or arthritis secondary to other inflammatory diseases; HIV, viral hepatitis; chondrocalcinosis, Paget's disease, or villonodular synovitis
• Diagnosed with leukemia, known presence of metastatic malignant cells, or ongoing or planned chemotherapeutic treatment
• Untreated symptomatic injury of the index knee
• Presence of surgical hardware or other foreign body intended to treat arthritis or cartilage-related pathology in the index knee
• Previous cartilage repair procedure on the injured cartilage surface of the index knee
• Arthroplasty or open surgery of the index knee within 6 months of screening
• Intra-articular steroid injection in the index knee within 3 months of screening
• Intra-articular hyaluronic acid injection in the index knee within 6 months of screening
• Other intra-articular therapy in the index knee within 6 months prior to screening
• Orally administered systemic steroid use within 2 weeks of screening
• Planned/anticipated surgery of the index knee during the study period
• Skin breakdown at the knee where the injection is planned to take place
• Pregnant or nursing mothers or women planning on getting pregnant during the time they will be participating in the study
• Participated in any investigational drug or device trial within 30 days prior to screening
• Participated in any investigational biologic trial within 60 days prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nSTRIDE APS; Autologous Protein Solution prepared using the nSTRIDE APS Kit	Device: nSTRIDE APS; single intra-articular injection; Other Names: Autologous Protein Solution
Other: Saline; Saline control	Device: Saline; single intra-articular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Likert (LK) 3.1 Pain Subscale Change From Baseline to 12 Months	The primary objective of this study was to determine whether nSTRIDE APS is superior to Saline with respect to the improvement in mean WOMAC Pain score (change from baseline to 12 Months post-injection raw score). The WOMAC pain subscale consisted of five questions scored from 0 to 4. The pain score has a range of 0 (no pain) to 20 (maximal pain).	Baseline and 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale (VAS) Pain Change From Baseline to 12 Months	The Visual Analogue Scale is a common tool for measuring general pain. A 100 mm line is marked from 0 to 10 in 10 mm increments. Knee pain severity is indicated by drawing a vertical mark at the point on the line that best represents the severity of pain. No pain is indicated by the 0 at the far left, and the worst possible pain is indicated by the 100 at the far right.	Baseline and 12 Months
Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Responders	The OMERACT-OARSI Responder Criteria were applied to both treatment groups, categorizing each patient into one of two categories: responder and non-responder. Responders were defined as subjects who achieved a high degree of improvement in pain or in function (improvement of ≥50% and absolute change ≥20), or a moderate degree of improvement in 2 of the 3 response domains (pain, function, global assessment).	12 months
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) LK 3.1 Stiffness Subscale Change From Baseline to 12 Months	The WOMAC stiffness subscale consisted of two questions scored from 0 to 4. The stiffness score has a range of 0 (no stiffness) to 8 (maximal stiffness).	Baseline and 12 Months
EQ-5D Change From Baseline to 12 Months	The EQ-5D is a validated instrument that assesses an individual's current health status and heath related quality of life. The EQ-5D-3L descriptive component assesses five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression over three levels of severity. The EQ visual analogue scale (EQ VAS) assesses the respondent's self-rated overall health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline and 12 Months
Adverse Events	Subjects experiencing at least one AE	12 months

Collaborators and Investigators

• Sponsor: Zimmer Biomet
• Investigators: Principal Investigator: Frederick M Azar, M.D., Campbell Clinic

Publications and helpful links

General Publications

• King W, van der Weegen W, Van Drumpt R, Soons H, Toler K, Woodell-May J. White blood cell concentration correlates with increased concentrations of IL-1ra and improvement in WOMAC pain scores in an open-label safety study of autologous protein solution. J Exp Orthop. 2016 Dec;3(1):9. doi: 10.1186/s40634-016-0043-7. Epub 2016 Feb 9.
• van Drumpt RA, van der Weegen W, King W, Toler K, Macenski MM. Safety and Treatment Effectiveness of a Single Autologous Protein Solution Injection in Patients with Knee Osteoarthritis. Biores Open Access. 2016 Aug 1;5(1):261-8. doi: 10.1089/biores.2016.0014. eCollection 2016.

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: September 14, 2016
• First Submitted That Met QC Criteria: September 14, 2016
• First Posted (Estimated): September 19, 2016

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: osteoarthritis; APS; intra-articular injection; Autologous Protein Solution
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: APSS-44-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: Yes