Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis, osteoarthritis of the knee
Brief summary
This study will evaluate the efficacy of an Intra-Articular Injection of Ampion™ in Adults with pain due to osteoarthritis of the knee.
Detailed description
A Randomized, Placebo-controlled, Double-Blind Study to Evaluate the Efficacy and Safety of an Intra-Articular Injection of Ampion™ in Adults with pain due to osteoarthritis of the knee. The primary study objective was to evaluate the efficacy of 4 mL Ampion versus 4 mL saline intra-articular (IA) injection in treating knee pain when administered to subjects suffering from osteoarthritis (OA) of the knee (OAK). The secondary study objectives included evaluation of the safety of an IA injection of Ampion vs saline, efficacy of IA injection of Ampion vs saline in improving knee function.
Interventions
BIOLOGICAL4 mL injection of Ampion
4 mL injection of Ampion
4 mL Injection of Placebo
Sponsors
Ampio Pharmaceuticals. Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, 35 years to 85 years old (inclusive) who are ambulatory but suffering from moderate to moderately severe pain from osteoarthritis in the index knee as evidenced by a rating of at least 1.5 on the WOMAC Index 3.1 5-point Likert Pain Subscale at screening. 2. Index knee must be symptomatic for greater than 6 months with a clinical diagnosis of OA and supported by radiological evidence (Kellgren Lawrence Grade II, III, IV). Confirmatory x-ray must be taken at Screening and assessed using Kellgren Lawrence grading system. 3. Moderate to moderately-severe OA pain in the index knee even with dosing of nonsteroidal anti-inflammatory drug (NSAID) in the 4 weeks prior to screening. 4. No analgesia (including acetaminophen \[paracetamol\]) taken 12 hours prior to an efficacy measure; and, 5. Able to provide written informed consent to participate in the study. 6. Willing and able to comply with all study requirements and instructions of the site study staff.
Exclusion criteria
1. Previous participation in an Ampion™ study. 2. Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or joint replacement in the affected knee, as assessed locally by the principal investigator. 3. Isolated patella femoral syndrome, also known as chondromalacia. 4. 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 OA). 5. Major injury to the index knee within the 12 months prior to screening. 6. Severe hip OA ipsilateral to the index knee. 7. Presence of tense effusions. 8. 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). 9. Initiation or change in any pharmacological or non-pharmacological treatment for OA during the 4 weeks prior to randomization or likely to be changed during the duration of the study. 10. Use of the following medications anticipated to be required during the study: * Intra-articular pain medications in the study knee * Analgesics containing opioids. (NSAIDs may be continued at levels preceding the study and acetaminophen is available as a rescue medication during the study from the provided supply.) * Topical treatment on osteoarthritis index knee needed during the study * Use of significant anticoagulant therapy, oral or injectable, during the study (aspirin and clopidogrel are allowed) * Systemic treatments that may interfere with safety or efficacy assessments during the study such as immunosuppressants 11. Use of corticosteroids \>10 mg prednisolone equivalent per day (if ≤10 mg prednisolone, the dose must be stable). 12. Use of human albumin treatment in the 3 months before randomization. 13. A history of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin is not an exclusion criterion). 14. A history of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan, sodium caprylate). 15. Principal Investigator considers the patient unfit for the study based on medical review and screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in WOMAC A Pain | Scored at Baseline and 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in WOMAC C 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. |
Participant flow
Recruitment details
Recruitment of subjects occurred in medical clinics during the months of January and February 2014.
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 Injection 4 mL Intra-articular injection of Ampion | 269 |
| Placebo 4 mL Injection 4 mL placebo intra-articular injection | 269 |
| Total | 538 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Withdrawal by Subject | 11 | 21 |
Baseline characteristics
| Characteristic | Ampion 4 mL Injection | Placebo 4 mL Injection | Total |
|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 9.5 | 61.2 years STANDARD_DEVIATION 9.6 | 60.6 years STANDARD_DEVIATION 9.2 |
| BMI (kg/m^2) | 34.2 kg/m^2 STANDARD_DEVIATION 8.1 | 34.2 kg/m^2 STANDARD_DEVIATION 7.6 | 34.2 kg/m^2 STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 18 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 253 Participants | 251 Participants | 504 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade II | 67 Participants | 66 Participants | 133 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade III | 105 Participants | 90 Participants | 195 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade IV | 97 Participants | 113 Participants | 210 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 7 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 48 Participants | 35 Participants | 83 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 5 Participants | 5 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 | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 214 Participants | 219 Participants | 433 Participants |
| Region of Enrollment United States | 269 participants | 269 participants | 538 participants |
| Sex: Female, Male Female | 151 Participants | 159 Participants | 310 Participants |
| Sex: Female, Male Male | 118 Participants | 110 Participants | 228 Participants |
| Weight (kg) | 96.1 kg STANDARD_DEVIATION 24 | 95.1 kg STANDARD_DEVIATION 21.9 | 95.6 kg STANDARD_DEVIATION 23 |
| WOMAC Function | 2.45 score on a scale STANDARD_DEVIATION 0.6 | 2.41 score on a scale STANDARD_DEVIATION 0.63 | 2.43 score on a scale STANDARD_DEVIATION 0.61 |
| WOMAC Pain | 2.38 score on a scale STANDARD_DEVIATION 0.56 | 2.38 score on a scale STANDARD_DEVIATION 0.58 | 2.38 score on a scale STANDARD_DEVIATION 0.57 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 269 | 0 / 269 |
| other Total, other adverse events | 65 / 269 | 71 / 269 |
| serious Total, serious adverse events | 6 / 269 | 4 / 269 |
Outcome results
Primary
Change in WOMAC A 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 weeks
Population: Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ampion 4 mL Injection | Change in WOMAC A Pain | -0.81 score on a scale |
| Placebo 4 mL Injection | Change in WOMAC A Pain | -0.81 score on a scale |
p-value: 0.97ANCOVA
Secondary
Change in WOMAC C 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 Injection | Change in WOMAC C Function | -0.76 score on a scale |
| Placebo 4 mL Injection | Change in WOMAC C Function | -0.77 score on a scale |
p-value: 0.75ANCOVA
Post Hoc
Change in WOMAC A Pain of KL Grade IV Subset
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 weeks
Population: Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ampion 4 mL Injection | Change in WOMAC A Pain of KL Grade IV Subset | -0.82 score on a scale |
| Placebo 4 mL Injection | Change in WOMAC A Pain of KL Grade IV Subset | -0.65 score on a scale |
p-value: 0.18ANCOVA
Post Hoc
Change in WOMAC C Function of KL Grade IV Subset
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 Injection | Change in WOMAC C Function of KL Grade IV Subset | -0.73 score on a scale |
| Placebo 4 mL Injection | Change in WOMAC C Function of KL Grade IV Subset | -0.69 score on a scale |
p-value: 0.81ANCOVA