Severe Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis, osteoarthritis of the knee
Brief summary
The purpose of this study is to confirm the safety and efficacy of Ampion for the treatment of pain and function in patients with severe osteoarthritis of the knee.
Detailed description
This study is a randomized, double-blind, single dose design. The co-primary trial objectives are to evaluate the greater efficacy for pain improvement and function improvement of 4 mL Ampion versus saline intra-articular (IA) injection when applied to patients suffering from severe osteoarthritis of the knee (OAK). Efficacy will primarily be assessed with WOMAC A pain and WOMAC C function scores. Mean change in the WOMAC A weekly pain scores from Baseline to Week 12 will be compared between Ampion and saline control. Mean change in WOMAC C function score will be compared between Ampion and saline control. This will test whether Ampion is superior to saline in improving pain and function.
Interventions
BIOLOGICALAmpion
4 mL injection of Ampion
DRUGSaline
Saline solution, 4 mL, single intra-articular injection
Sponsors
Ampio Pharmaceuticals. Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Able to provide written informed consent to participate in the study * Willing and able to comply with all study requirements and instructions of the site study staff * Must be ambulatory * Index knee must be symptomatic for greater than 6 months with a clinical diagnosis of OAK and supported by radiological evidence (Kellgren-Lawrence Grade 4) that is not older than 6 months prior to the date of screening * Moderate to moderately-severe osteoarthritis (OA) pain in the index knee (rating of at least 1.5 on the WOMAC Index 3.1 as measured by 5-point Likert Pain Subscale) assessed at screening * Ability to temporarily discontinue nonsteroidal anti-inflammatory drug (NSAID) for 48 hours prior to scheduled clinical efficacy evaluations * No analgesia (including acetaminophen \[paracetamol\]) taken 12 hours prior to an efficacy measure * No known clinically significant liver abnormality (e.g. cirrhosis, transplant, etc.).
Exclusion criteria
* As a result of medical review and screening investigation, the Principal Investigator considers the patient unfit for the study * A history of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin is not an exclusion criterion) * A history of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan, sodium caprylate) * Presence of tense effusions * Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or joint replacement in the affected knee, as assessed locally by the Principal Investigator * Isolated patella femoral syndrome, also known as chondromalacia * Any other disease or condition interfering with the free use and evaluation of the index knee for the duration of the trial (e.g. cancer, congenital defects, spine osteoarthritis) * Major injury to the index knee within the 12 months prior to screening * Severe hip osteoarthritis ipsilateral to the index knee * Any pain that could interfere with the assessment of index knee pain (e.g. pain in any other part of the lower extremities, pain radiating to the knee) * Any pharmacological or non-pharmacological treatment targeting OA started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study * Use of the following medications: 1. No IA injected pain medications in the study knee during the study 2. No analgesics containing opioids. NSAIDs may be continued at levels preceding the study, however may not be used 48 hours prior to efficacy evaluations, and acetaminophen is available as a rescue medication during the study from the provided supply 3. No topical treatment on osteoarthritis index knee during the study 4. No significant anticoagulant therapy (e.g. Heparin or Lovenox) during the study (treatment such as Aspirin and Plavix are allowed) 5. No systemic treatments that may interfere with safety or efficacy assessments during the study 6. No immunosuppressants 7. No use of corticosteroids \> 10 mg prednisolone equivalent per day 8. If corticosteroid use is ≤ 10 mg prednisolone equivalent per day, and if clinically indicated, subjects should be allowed to decrease their corticosteroid use. Additionally, some subjects may need to increase their steroid dose to treat worsened symptoms in the treated knee, and subjects who increase their corticosteroid dose above their starting dose of corticosteroid during the study will be treated as treatment failures for efficacy analysis * No human albumin treatment in the 3 months before randomization or throughout the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Knee Pain | Scored at Baseline and 12 Week | Mean Change in WOMAC A Pain (Western Ontario and McMaster Universities Arthritis Index) score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a decrease in pain with a greater negative value indicating a greater reduction in pain. |
| Change in Knee Function | Scored at Baseline and 12 weeks. | Mean change in WOMAC C function score (Western Ontario and McMaster Universities Arthritis Index) from Baseline to 12 weeks. 5-point Likert scale indicating limitation of function (0=none to 4=extreme). A greater negative value indicates a improvement in function. |
Countries
United States
Participant flow
Recruitment details
Recruitment of subjects occurred in medical clinics from June 2019 to March 2020.
Pre-assignment details
No pharmacological or non-pharmacological treatment targeting osteoarthritis (OA) started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study.
Participants by arm
| Arm | Count |
|---|---|
| Ampion 4 mL Dose 4 mL Injection of Ampion | 520 |
| Placebo 4 mL Dose 4 mL Injection of Placebo | 523 |
| Total | 1,043 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | COVID-19 pandemic | 225 | 227 |
| Overall Study | Lack of Efficacy | 3 | 1 |
| Overall Study | Lost to Follow-up | 5 | 8 |
| Overall Study | Non-compliance | 3 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Sponsor decision to terminate follow up | 10 | 12 |
| Overall Study | Withdrawal by Subject | 39 | 37 |
Baseline characteristics
| Characteristic | Placebo 4 mL Dose | Total | Ampion 4 mL Dose |
|---|---|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 9.2 | 64.7 years STANDARD_DEVIATION 9.2 | 64.7 years STANDARD_DEVIATION 9.2 |
| Body Mass Index (BMI) | 34.7 kg/m^2 STANDARD_DEVIATION 8.5 | 34.3 kg/m^2 STANDARD_DEVIATION 8.3 | 33.8 kg/m^2 STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 51 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 495 Participants | 986 Participants | 491 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 83 Participants | 181 Participants | 98 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 12 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 429 Participants | 839 Participants | 410 Participants |
| Region of Enrollment United States | 523 participants | 1043 participants | 520 participants |
| Sex: Female, Male Female | 342 Participants | 646 Participants | 304 Participants |
| Sex: Female, Male Male | 181 Participants | 397 Participants | 216 Participants |
| WOMAC Function | 2.45 Score on a scale STANDARD_DEVIATION 0.72 | 2.44 Score on a scale STANDARD_DEVIATION 0.71 | 2.43 Score on a scale STANDARD_DEVIATION 0.7 |
| WOMAC Pain | 2.40 Score on a scale STANDARD_DEVIATION 0.7 | 2.37 Score on a scale STANDARD_DEVIATION 0.69 | 2.34 Score on a scale STANDARD_DEVIATION 0.69 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 520 | 0 / 523 |
| other Total, other adverse events | 154 / 520 | 162 / 523 |
| serious Total, serious adverse events | 16 / 520 | 11 / 523 |
Outcome results
Primary
Change in Knee Function
Mean change in WOMAC C function score (Western Ontario and McMaster Universities Arthritis Index) from Baseline to 12 weeks. 5-point Likert scale indicating limitation of function (0=none to 4=extreme). A greater negative value indicates a improvement in function.
Time frame: Scored at Baseline and 12 weeks.
Population: Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ampion 4 mL Dose | Change in Knee Function | -0.68 Score on a scale |
| Placebo 4 mL Dose | Change in Knee Function | -0.73 Score on a scale |
p-value: 0.3MMRM
Primary
Change in Knee Pain
Mean Change in WOMAC A Pain (Western Ontario and McMaster Universities Arthritis Index) score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a decrease in pain with a greater negative value indicating a greater reduction in pain.
Time frame: Scored at Baseline and 12 Week
Population: Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ampion 4 mL Dose | Change in Knee Pain | -0.66 Score on a scale |
| Placebo 4 mL Dose | Change in Knee Pain | -0.71 Score on a scale |
p-value: 0.32MMRM