Gonarthrosis, Knee Osteoarthritis, Osteoarthritis
Conditions
Keywords
Autologous Protein Solution, APS, Osteoarthritis, Injection
Brief summary
This prospective single-center study will evaluate the safety and tolerability of a single dose of APS(TM) treated patients with OA of the knee who have failed conservative OA therapy. The study will also evaluate efficacy by assessing patient pain and functionality.
Interventions
DEVICEAutologous Protein Solution APS(TM)
A therapy prepared at the point-of-care from a small sample of the patient's own blood containing high concentrations of anti-inflammatory and anabolic proteins
Sponsors
Zimmer Biomet
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligibility Criteria: * Male or female ≥40 years. * Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions. * A standing radiograph of the knee showing a Kellgren grade of 2 or 3 * Frequency of knee pain on most days over the last month. * Diagnosis of unilateral knee OA * Body mass index (BMI) ≤40 kg/m2. * Failed conservative OA therapy. * Signed an independent ethics committee (IEC)-approved informed consent form (ICF). * Willingness to abstain from the use of topical pain therapies, intra-articular corticosteroids, and viscosupplementation during the study. * Willingness to abstain from systemic pain medications except rescue medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | Up to 6 months post-injection | Safety and tolerability will be assessed from AEs and injection-site reactions, physical examinations, knee examinations, vital signs, ECGs, and clinical laboratory tests (hematology, coagulation, blood chemistry, and urinalysis) evaluated at baseline (pre-injection) and post-injection up to 6 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physical Function Score | Baseline, Week 1, Week 2, and at Months 1, 3, and 6. | Changed Outcome Measure Description to: The Western Ontario and McMaster Universities osteoarthritis index questionnaire using the Likert scale (WOMAC LK), Version 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item was to be answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). The scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. A higher score indicates worse pain, stiffness, or functional limitation. |
| Number of Patients Using Rescue Medication | Up to 6 months post-injection | Explore the potential for an analgesic effect of a single dose of APS in patients with OA of the knee. |
| Pain Score | Baseline, Week 1, Week 2, and at Months 1, 3, and 6. | The Western Ontario and McMaster Universities osteoarthritis index questionnaire using the Likert scale (WOMAC LK), Version 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item was to be answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). The scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. A higher score indicates worse pain, stiffness, or functional limitation. |
| Stiffness Score | Baseline, Week 1, Week 2, and at Months 1, 3, and 6. | Changed Outcome Measure Description to: The Western Ontario and McMaster Universities osteoarthritis index questionnaire using the Likert scale (WOMAC LK), Version 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item was to be answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). The scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. A higher score indicates worse pain, stiffness, or functional limitation. |
Countries
Netherlands
Participant flow
Recruitment details
Single-centre study in the Netherlands. FPI April 2013.
Pre-assignment details
All patients treated with APS who had at least 1 post-injection assessment of clinical outcomes were to be included in the clinical outcomes population, which was used for the clinical outcomes summaries and listings
Participants by arm
| Arm | Count |
|---|---|
| Autologous Protein Solution APS(TM) Patients who have been treated with a single, intra-articular injection.
Autologous Protein Solution APS(TM): A therapy prepared at the point-of-care from a small sample of the patient's own blood containing high concentrations of anti-inflammatory and anabolic proteins | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Autologous Protein Solution APS(TM) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 57 Years STANDARD_DEVIATION 9.5 |
| Region of Enrollment Netherlands | 11 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Number of Adverse Events
Safety and tolerability will be assessed from AEs and injection-site reactions, physical examinations, knee examinations, vital signs, ECGs, and clinical laboratory tests (hematology, coagulation, blood chemistry, and urinalysis) evaluated at baseline (pre-injection) and post-injection up to 6 months.
Time frame: Up to 6 months post-injection
Population: In cases where a patient reported multiple occurrences of an AE, the first occurrence of the worst reported case of the event was to be used for the purpose of analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autologous Protein Solution APS(TM) | Number of Adverse Events | 22 Adverse Events (AEs) |
Secondary
Number of Patients Using Rescue Medication
Explore the potential for an analgesic effect of a single dose of APS in patients with OA of the knee.
Time frame: Up to 6 months post-injection
Population: The incidence of patients using rescue medication for OA pain.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Autologous Protein Solution APS(TM) | Number of Patients Using Rescue Medication | Injection visit | 2 Frequency of Patients using Rescue medic |
| Autologous Protein Solution APS(TM) | Number of Patients Using Rescue Medication | Month 6 | 2 Frequency of Patients using Rescue medic |
Secondary
Pain Score
The Western Ontario and McMaster Universities osteoarthritis index questionnaire using the Likert scale (WOMAC LK), Version 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item was to be answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). The scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. A higher score indicates worse pain, stiffness, or functional limitation.
Time frame: Baseline, Week 1, Week 2, and at Months 1, 3, and 6.
Population: Results of the WOMAC LK 3.1 questionnaire (pain, stiffness, and functionality subscores) were summarized by timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Protein Solution APS(TM) | Pain Score | Baseline | 12 Scores on a WOMAC pain scale | Standard Deviation 1.6 |
| Autologous Protein Solution APS(TM) | Pain Score | Week 1 | 8.2 Scores on a WOMAC pain scale | Standard Deviation 5.1 |
| Autologous Protein Solution APS(TM) | Pain Score | Week 2 | 6.5 Scores on a WOMAC pain scale | Standard Deviation 4.7 |
| Autologous Protein Solution APS(TM) | Pain Score | Month 1 | 4.5 Scores on a WOMAC pain scale | Standard Deviation 4.1 |
| Autologous Protein Solution APS(TM) | Pain Score | Month 3 | 3.0 Scores on a WOMAC pain scale | Standard Deviation 3.1 |
| Autologous Protein Solution APS(TM) | Pain Score | Month 6 | 3.1 Scores on a WOMAC pain scale | Standard Deviation 4.3 |
Secondary
Physical Function Score
Changed Outcome Measure Description to: The Western Ontario and McMaster Universities osteoarthritis index questionnaire using the Likert scale (WOMAC LK), Version 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item was to be answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). The scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. A higher score indicates worse pain, stiffness, or functional limitation.
Time frame: Baseline, Week 1, Week 2, and at Months 1, 3, and 6.
Population: Results of the WOMAC LK 3.1 questionnaire (pain, stiffness, and functionality subscores) were summarized by timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Protein Solution APS(TM) | Physical Function Score | Baseline | 38.1 Scores on a WOMAC functionality scale | Standard Deviation 7.5 |
| Autologous Protein Solution APS(TM) | Physical Function Score | Week 1 | 27.8 Scores on a WOMAC functionality scale | Standard Deviation 16.2 |
| Autologous Protein Solution APS(TM) | Physical Function Score | Week 2 | 21.9 Scores on a WOMAC functionality scale | Standard Deviation 13.4 |
| Autologous Protein Solution APS(TM) | Physical Function Score | Month 1 | 17.5 Scores on a WOMAC functionality scale | Standard Deviation 15.1 |
| Autologous Protein Solution APS(TM) | Physical Function Score | Month 3 | 10 Scores on a WOMAC functionality scale | Standard Deviation 11.4 |
| Autologous Protein Solution APS(TM) | Physical Function Score | Month 6 | 12.3 Scores on a WOMAC functionality scale | Standard Deviation 14.7 |
Secondary
Stiffness Score
Changed Outcome Measure Description to: The Western Ontario and McMaster Universities osteoarthritis index questionnaire using the Likert scale (WOMAC LK), Version 3.1 questionnaire has 24 items that the patient addresses about the knee: 5 items on the pain subscale, 2 on the stiffness subscale, and 17 on the physical function subscale. Each item was to be answered on a 5-point Likert scale, with grading from 0 (none or never) to 4 (extreme or always). The scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. A higher score indicates worse pain, stiffness, or functional limitation.
Time frame: Baseline, Week 1, Week 2, and at Months 1, 3, and 6.
Population: Results of the WOMAC LK 3.1 questionnaire (pain, stiffness, and functionality subscores) were summarized by timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Protein Solution APS(TM) | Stiffness Score | Baseline | 4.9 Scores on a WOMAC stiffness scale | Standard Deviation 0.9 |
| Autologous Protein Solution APS(TM) | Stiffness Score | Week 1 | 3.8 Scores on a WOMAC stiffness scale | Standard Deviation 1.7 |
| Autologous Protein Solution APS(TM) | Stiffness Score | Week 2 | 3.1 Scores on a WOMAC stiffness scale | Standard Deviation 1.2 |
| Autologous Protein Solution APS(TM) | Stiffness Score | Month 1 | 2.5 Scores on a WOMAC stiffness scale | Standard Deviation 1.8 |
| Autologous Protein Solution APS(TM) | Stiffness Score | Month 3 | 1.7 Scores on a WOMAC stiffness scale | Standard Deviation 1.8 |
| Autologous Protein Solution APS(TM) | Stiffness Score | Month 6 | 2.3 Scores on a WOMAC stiffness scale | Standard Deviation 1.9 |