Osteoarthritis
Conditions
Keywords
Autologous Protein Solution, APS, intra-articular injection, osteoarthritis
Brief summary
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.
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.
Interventions
DEVICEnSTRIDE APS
single intra-articular injection
DEVICESaline
single intra-articular injection
Sponsors
Zimmer Biomet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Likert (LK) 3.1 Pain Subscale Change From Baseline to 12 Months | Baseline and 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale (VAS) Pain Change From Baseline to 12 Months | Baseline and 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. |
| Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Responders | 12 months | 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). |
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) LK 3.1 Stiffness Subscale Change From Baseline to 12 Months | Baseline and 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). |
| EQ-5D Change From Baseline to 12 Months | Baseline and 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). |
| Adverse Events | 12 months | Subjects experiencing at least one AE |
Countries
United States
Participant flow
Pre-assignment details
During the screening process, potential subjects provided informed consent and were then screened for eligibility. Screening consisted of meeting all inclusion and exclusion criteria, including a WOMAC LK 3.1 pain subscale score ≥ 9 and ≤ 19 and by providing objective physiological evidence of OA using the Kellgren-Lawrence scale (assessed from normal radiographs).
Participants by arm
| Arm | Count |
|---|---|
| nSTRIDE APS Autologous Protein Solution prepared using the nSTRIDE APS Kit
nSTRIDE APS: single intra-articular injection | 172 |
| Saline Saline control
Saline: single intra-articular injection | 160 |
| Total | 332 |
Baseline characteristics
| Characteristic | Saline | Total | nSTRIDE APS |
|---|---|---|---|
| Age, Continuous | 58.6 years STANDARD_DEVIATION 9.6 | 58.55 years STANDARD_DEVIATION 9.95 | 58.5 years STANDARD_DEVIATION 10.3 |
| Race/Ethnicity, Customized African-American | 13 Participants | 27 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian or Pacific Islander | 1 Participants | 6 Participants | 5 Participants |
| Race/Ethnicity, Customized Native American | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Specified | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 7 Participants | 5 Participants |
| Race/Ethnicity, Customized White (Hispanic) | 7 Participants | 28 Participants | 21 Participants |
| Race/Ethnicity, Customized White (Non-Hispanic) | 135 Participants | 260 Participants | 125 Participants |
| Region of Enrollment United States | 160 participants | 332 participants | 172 participants |
| Sex: Female, Male Female | 90 Participants | 170 Participants | 80 Participants |
| Sex: Female, Male Male | 70 Participants | 162 Participants | 92 Participants |
| WOMAC Pain | 11.37 points STANDARD_DEVIATION 2.11 | 11.32 points STANDARD_DEVIATION 2.17 | 11.27 points STANDARD_DEVIATION 2.23 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 172 | 1 / 160 |
| other Total, other adverse events | 0 / 172 | 0 / 160 |
| serious Total, serious adverse events | 8 / 172 | 8 / 160 |
Outcome results
Primary
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).
Time frame: Baseline and 12 Months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| nSTRIDE APS | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Likert (LK) 3.1 Pain Subscale Change From Baseline to 12 Months | -5.6 score on a scale |
| Saline | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Likert (LK) 3.1 Pain Subscale Change From Baseline to 12 Months | -5.4 score on a scale |
Secondary
Adverse Events
Subjects experiencing at least one AE
Time frame: 12 months
Population: Intent to Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| nSTRIDE APS | Adverse Events | 94 Participants |
| Saline | Adverse Events | 93 Participants |
Secondary
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).
Time frame: Baseline and 12 Months
Population: Number of subjects with a completed EQ-5D score at Baseline and at 12 Months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| nSTRIDE APS | EQ-5D Change From Baseline to 12 Months | 4.62 score on a scale |
| Saline | EQ-5D Change From Baseline to 12 Months | 4.06 score on a scale |
Secondary
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).
Time frame: 12 months
Population: Number of subjects with complete data at 12 Months to calculate responder status
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| nSTRIDE APS | Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Responders | Responder | 101 Participants |
| nSTRIDE APS | Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Responders | Non-Responder | 48 Participants |
| Saline | Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Responders | Responder | 92 Participants |
| Saline | Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Responders | Non-Responder | 42 Participants |
Secondary
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.
Time frame: Baseline and 12 Months
Population: Number of subjects with a completed VAS pain score at Baseline and at 12 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| nSTRIDE APS | Visual Analog Scale (VAS) Pain Change From Baseline to 12 Months | -25.8 score on a scale | Standard Deviation 27.09 |
| Saline | Visual Analog Scale (VAS) Pain Change From Baseline to 12 Months | -23.4 score on a scale | Standard Deviation 29.14 |
Secondary
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).
Time frame: Baseline and 12 Months
Population: Number of subjects with a completed WOMAC stiffness score at Baseline and at 12 Months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| nSTRIDE APS | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) LK 3.1 Stiffness Subscale Change From Baseline to 12 Months | -2.1 score on a scale |
| Saline | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) LK 3.1 Stiffness Subscale Change From Baseline to 12 Months | -2.2 score on a scale |
Post Hoc
Post-Hoc Pain/Medication Usage Responder Analysis
This criteria is based on the usage of rescue medication and restricted medication/therapy usage and the WOMAC pain subscale percent change from baseline. A patient is considered a non-responder if one or more of the following are true: 1. Early exit for Knee OA per IDMC determination 2. WOMAC Pain Percent improvement 27% 3. Rescue Medication not withheld within 48 hours of the 12 month study visit 4. Medication/therapy violation at the 12 month visit (New or Continuing) 5. Rescue medication taken most days or every day, as reported at the 12 month visit
Time frame: Baseline and 1 Year
Population: Per Protocol population at 12 Months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| nSTRIDE APS | Post-Hoc Pain/Medication Usage Responder Analysis | Responder | 97 Participants |
| nSTRIDE APS | Post-Hoc Pain/Medication Usage Responder Analysis | Non-Responder | 65 Participants |
| Saline | Post-Hoc Pain/Medication Usage Responder Analysis | Responder | 71 Participants |
| Saline | Post-Hoc Pain/Medication Usage Responder Analysis | Non-Responder | 80 Participants |