Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis, Osteoarthritis of the Knee
Brief summary
This study will evaluate the efficacy and safety 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 trial objective is to evaluate the efficacy of 4 mL of 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 is evaluation of the safety of an intra-articular injection of AMPION™.
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
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 OA and supported by radiological evidence (Kellgren Lawrence Grade II, III, or IV) read by a central reader; * WOMAC 5-point Likert pain subscale \<1.5 in the contralateral knee; * 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); * 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); * Ability to discontinue NSAID use at Screening visit and/or 72 hours prior to the Baseline visit and for the duration of the clinical study (low dose Aspirin is allowed during the study); * No analgesia (including acetaminophen \[paracetamol\]) taken 24 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 * Pregnancy or planning to become pregnant during the study. * Use of the following medications: * No IA injected pain medications in the study knee during the study * No analgesics containing opioids. * NSAIDs are not permitted during the study; acetaminophen is available as a rescue medication during the study from the provided supply. * No topical treatment on osteoarthritis index knee during the study * No significant anticoagulant therapy (e.g. Heparin or Lovenox) during the study (treatment such as low dose Aspirin and Plavix are allowed) * No systemic treatments that may interfere with safety or efficacy assessments during the study * No immunosuppressants * No use of corticosteroids * 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 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. |
Countries
United States
Participant flow
Recruitment details
Subjects will be recruited from the population being seen by Investigators at the clinical sites participating in the study. In addition, notifications about the opportunity for subjects to participate in a clinical trial will be sent to referring physicians.
Pre-assignment details
Ability to discontinue NSAID use at Screening visit and/or 72 hours prior to the Baseline visit and for the duration of the clinical study. No analgesia (including acetaminophen \[paracetamol\]) taken 24 hours prior to an efficacy measure.
Participants by arm
| Arm | Count |
|---|---|
| 4 mL AMPION™ AMPION™: 4 mL Ampion Injection | 237 |
| 4 mL Saline Placebo Saline: 4 mL Saline Injection | 243 |
| Total | 480 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Missing reason | 3 | 1 |
| Overall Study | Moved out of state | 1 | 0 |
| Overall Study | Pain as lack of efficacy | 0 | 4 |
| Overall Study | Required proscribed pain medication | 2 | 1 |
| Overall Study | Surgical treatment | 3 | 0 |
| Overall Study | Worsening osteoarthritis | 1 | 0 |
Baseline characteristics
| Characteristic | 4 mL AMPION™ | 4 mL Saline Placebo | Total |
|---|---|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 9.05 | 60.8 years STANDARD_DEVIATION 8.84 | 61.2 years STANDARD_DEVIATION 8.95 |
| BMI (kg/m^2) | 32.94 kg/m^2 STANDARD_DEVIATION 6.98 | 33.91 kg/m^2 STANDARD_DEVIATION 7.58 | 33.43 kg/m^2 STANDARD_DEVIATION 7.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 15 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 219 Participants | 228 Participants | 447 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Kellgren Lawrence Grade Kellgren-Lawrence Grade II | 50 Participants | 51 Participants | 101 Participants |
| Kellgren Lawrence Grade Kellgren-Lawrence Grade III | 122 Participants | 125 Participants | 247 Participants |
| Kellgren Lawrence Grade Kellgren-Lawrence Grade IV | 65 Participants | 67 Participants | 132 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 51 Participants | 42 Participants | 93 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 180 Participants | 197 Participants | 377 Participants |
| Region of Enrollment United States | 237 participants | 243 participants | 480 participants |
| Sex: Female, Male Female | 159 Participants | 152 Participants | 311 Participants |
| Sex: Female, Male Male | 78 Participants | 91 Participants | 169 Participants |
| Weight (kg) | 91.49 kg STANDARD_DEVIATION 22.38 | 95.19 kg STANDARD_DEVIATION 22.32 | 93.36 kg STANDARD_DEVIATION 22.41 |
| WOMAC Function | 2.37 score on a scale STANDARD_DEVIATION 0.64 | 2.34 score on a scale STANDARD_DEVIATION 0.6 | 2.36 score on a scale STANDARD_DEVIATION 0.62 |
| WOMAC Pain | 2.37 score on a scale STANDARD_DEVIATION 0.56 | 2.33 score on a scale STANDARD_DEVIATION 0.53 | 2.35 score on a scale STANDARD_DEVIATION 0.54 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 236 | 0 / 243 |
| other Total, other adverse events | 47 / 236 | 44 / 243 |
| serious Total, serious adverse events | 2 / 236 | 4 / 243 |
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) |
|---|---|---|
| 4 mL AMPION™ | Change in Knee Pain | -0.91 score on a scale |
| 4 mL Saline Placebo | Change in Knee Pain | -0.89 score on a scale |
p-value: 0.94ANCOVA
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: Per Protocol (PP)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 4 mL AMPION™ | Change in Knee Function | -1.04 score on a scale |
| 4 mL Saline Placebo | Change in Knee Function | -0.97 score on a scale |
p-value: 0.53ANCOVA
Post Hoc
Change in Knee Pain of Kellgren-Lawrence 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: KL Grade IV Subset of Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 4 mL AMPION™ | Change in Knee Pain of Kellgren-Lawrence Grade IV Subset | -0.81 score on a scale |
| 4 mL Saline Placebo | Change in Knee Pain of Kellgren-Lawrence Grade IV Subset | -0.62 score on a scale |
p-value: 0.35ANCOVA