Osteoarthritis of the Knee
Conditions
Keywords
osteoarthritis, osteoarthritis of the knee
Brief summary
This study will evaluate the efficacy of two doses of 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 two Doses of Intra-Articular Injection of Ampion™ in Adults with pain due to osteoarthritis of the knee. The primary trial objective is to evaluate whether there is greater efficacy of 10 mL Ampion™ versus 10 mL placebo than 4 mL Ampion™ versus 4 mL placebo intra-articular (IA) injection in improving knee pain, when applied to patients suffering from OA of the knee. The secondary trial objective include: the evaluation of the safety of an intra-articular injection of Ampion™ when applied to patients suffering from OA of the knee, evaluation of the efficacy of intra-articular injection of Ampion™ and placebo on stiffness and function when applied to patients suffering from OA of the knee and evaluation of responder status defined by the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) Criteria.
Interventions
BIOLOGICAL4 mL injection of Ampion
4 mL Injection of Ampion
BIOLOGICAL10 mL Injection of Ampion
10 mL Injection of Ampion
4 mL Injection of Placebo
DRUG10 mL Injection of Placebo
10 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
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 * Male or female, 40 years to 85 years old (inclusive) * Must be ambulatory * Index knee must be symptomatic for greater than 6 months with a clinical diagnosis of osteoarthritis (OA) and supported by radiological evidence Kellgren Lawrence Grade II to IV) that is not older than 6 months prior to the date of screening * Moderate to moderately-severe OA pain in the index knee (rating of at least 1.5 on the WOMAC Index 3.1 5-point Likert Pain Subscale) assessed at screening * Moderate to moderately-severe OA pain in the index knee (even if chronic doses of nonsteroidal anti-inflammatory drug (NSAID), which have not changed in the 4 weeks prior to screening, have been/are being used) * 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 OA) * Major injury to the index knee within the 12 months prior to screening * Severe hip OA 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 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 (if ≤ 10 mg prednisolone, the dose must be stable) * Any human albumin treatment in the 3 months before randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Knee 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 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. |
| Change in Knee Stiffness. | Scored at Baseline and 12 weeks. | Mean Change in WOMAC B stiffness score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a reduction in stiffness. |
| Change in Patient's Global Assessment | Scored at Baseline and 12 weeks. | Patients are asked the following question: Considering all the ways in which your arthritis affects you, please indicate how you are doing. 5-point Likert scale (0 = very well, 1 = well, 2 = fair, 3 = poor, 4 = very poor). A negative value constitutes an improvement in patient's assessment of disease severity. |
Participant flow
Recruitment details
Recruitment of subjects occurred in medical clinics during the months of March, April, and May 2013.
Pre-assignment details
No 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.
Participants by arm
| Arm | Count |
|---|---|
| Ampion 4 mL Dose 4 mL Injection of Ampion | 83 |
| Placebo 4 mL Dose 4 mL Injection of Placebo | 83 |
| Ampion 10 mL Dose 10 mL Injection of Ampion | 82 |
| Placebo 10 mL Dose 10 mL Injection of Placebo | 81 |
| Total | 329 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Early Termination | 3 | 0 | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 6 | 4 | 3 |
Baseline characteristics
| Characteristic | Ampion 4 mL Dose | Placebo 4 mL Dose | Ampion 10 mL Dose | Placebo 10 mL Dose | Total |
|---|---|---|---|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 9.27 | 60.7 years STANDARD_DEVIATION 8.27 | 62.8 years STANDARD_DEVIATION 8.36 | 63.8 years STANDARD_DEVIATION 9.95 | 62.48 years STANDARD_DEVIATION 9.02 |
| BMI (kg/m^2) | 33.2 kg/m^2 STANDARD_DEVIATION 7.76 | 34.5 kg/m^2 STANDARD_DEVIATION 8.02 | 32.8 kg/m^2 STANDARD_DEVIATION 6.58 | 32.1 kg/m^2 STANDARD_DEVIATION 6.46 | 33.16 kg/m^2 STANDARD_DEVIATION 7.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 83 Participants | 83 Participants | 80 Participants | 79 Participants | 325 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade II | 28 Participants | 29 Participants | 32 Participants | 26 Participants | 115 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade III | 38 Participants | 32 Participants | 35 Participants | 34 Participants | 139 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade IV | 17 Participants | 22 Participants | 15 Participants | 21 Participants | 75 Participants |
| Patient's Global Assessment (PGA) | 3.35 score on a scale STANDARD_DEVIATION 0.652 | 3.40 score on a scale STANDARD_DEVIATION 0.811 | 3.35 score on a scale STANDARD_DEVIATION 0.822 | 3.42 score on a scale STANDARD_DEVIATION 0.652 | 3.38 score on a scale STANDARD_DEVIATION 0.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 8 Participants | 8 Participants | 4 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 74 Participants | 74 Participants | 74 Participants | 77 Participants | 299 Participants |
| Region of Enrollment United States | 83 participants | 83 participants | 82 participants | 81 participants | 329 participants |
| Sex: Female, Male Female | 56 Participants | 57 Participants | 46 Participants | 50 Participants | 209 Participants |
| Sex: Female, Male Male | 27 Participants | 26 Participants | 36 Participants | 31 Participants | 120 Participants |
| Weight (kg) | 95.6 kg STANDARD_DEVIATION 22.15 | 98.4 kg STANDARD_DEVIATION 25.28 | 95.2 kg STANDARD_DEVIATION 22.42 | 90.6 kg STANDARD_DEVIATION 22.07 | 94.98 kg STANDARD_DEVIATION 23.08 |
| WOMAC Function | 2.13 score on a scale STANDARD_DEVIATION 0.564 | 2.25 score on a scale STANDARD_DEVIATION 0.626 | 2.23 score on a scale STANDARD_DEVIATION 0.61 | 2.22 score on a scale STANDARD_DEVIATION 0.616 | 2.21 score on a scale STANDARD_DEVIATION 0.6 |
| WOMAC Pain | 2.22 score on a scale STANDARD_DEVIATION 0.49 | 2.32 score on a scale STANDARD_DEVIATION 0.548 | 2.19 score on a scale STANDARD_DEVIATION 0.512 | 2.23 score on a scale STANDARD_DEVIATION 0.602 | 2.24 score on a scale STANDARD_DEVIATION 0.54 |
| WOMAC Stiffness | 2.25 score on a scale STANDARD_DEVIATION 0.717 | 2.36 score on a scale STANDARD_DEVIATION 0.798 | 2.43 score on a scale STANDARD_DEVIATION 0.781 | 2.44 score on a scale STANDARD_DEVIATION 0.768 | 2.37 score on a scale STANDARD_DEVIATION 0.77 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 83 | 0 / 83 | 0 / 82 | 0 / 81 |
| other Total, other adverse events | 23 / 83 | 38 / 83 | 17 / 82 | 29 / 81 |
| serious Total, serious adverse events | 0 / 83 | 2 / 83 | 3 / 82 | 2 / 81 |
Outcome results
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 weeks
Population: Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ampion Combined (4 mL & 10 mL Dose) | Change in Knee Pain | -0.93 score on a scale |
| Placebo Combined (4 mL and 10 mL Dose) | Change in Knee Pain | -0.72 score on a scale |
| Ampion 4 mL Dose | Change in Knee Pain | -0.93 score on a scale |
| Placebo 4 mL Dose | Change in Knee Pain | -0.71 score on a scale |
| Ampion 10 mL Dose | Change in Knee Pain | -0.92 score on a scale |
| Placebo 10 mL Dose | Change in Knee Pain | -0.73 score on a scale |
p-value: 0.004ANOVA
p-value: 0.017ANOVA
p-value: 0.093ANOVA
Secondary
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 Combined (4 mL & 10 mL Dose) | Change in Knee Function | -0.78 score on a scale |
| Placebo Combined (4 mL and 10 mL Dose) | Change in Knee Function | -0.64 score on a scale |
| Ampion 4 mL Dose | Change in Knee Function | -0.72 score on a scale |
| Placebo 4 mL Dose | Change in Knee Function | -0.58 score on a scale |
| Ampion 10 mL Dose | Change in Knee Function | -0.83 score on a scale |
| Placebo 10 mL Dose | Change in Knee Function | -0.69 score on a scale |
p-value: 0.0442ANOVA
Secondary
Change in Knee Stiffness.
Mean Change in WOMAC B stiffness score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a reduction in stiffness.
Time frame: Scored at Baseline and 12 weeks.
Population: Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ampion Combined (4 mL & 10 mL Dose) | Change in Knee Stiffness. | -0.72 score on a scale |
| Placebo Combined (4 mL and 10 mL Dose) | Change in Knee Stiffness. | -0.67 score on a scale |
| Ampion 4 mL Dose | Change in Knee Stiffness. | -0.66 score on a scale |
| Placebo 4 mL Dose | Change in Knee Stiffness. | -0.55 score on a scale |
| Ampion 10 mL Dose | Change in Knee Stiffness. | -0.79 score on a scale |
| Placebo 10 mL Dose | Change in Knee Stiffness. | -0.80 score on a scale |
p-value: 0.4133ANOVA
Secondary
Change in Patient's Global Assessment
Patients are asked the following question: Considering all the ways in which your arthritis affects you, please indicate how you are doing. 5-point Likert scale (0 = very well, 1 = well, 2 = fair, 3 = poor, 4 = very poor). A negative value constitutes an improvement in patient's assessment of disease severity.
Time frame: Scored at Baseline and 12 weeks.
Population: Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ampion Combined (4 mL & 10 mL Dose) | Change in Patient's Global Assessment | -0.87 score on a scale |
| Placebo Combined (4 mL and 10 mL Dose) | Change in Patient's Global Assessment | -0.65 score on a scale |
| Ampion 4 mL Dose | Change in Patient's Global Assessment | -0.96 score on a scale |
| Placebo 4 mL Dose | Change in Patient's Global Assessment | -0.55 score on a scale |
| Ampion 10 mL Dose | Change in Patient's Global Assessment | -0.77 score on a scale |
| Placebo 10 mL Dose | Change in Patient's Global Assessment | -0.74 score on a scale |
p-value: 0.0122ANOVA