Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis, osteoarthritis of the knee
Brief summary
This study will evaluate the efficacy of three intra-articular injections, given 2 weeks apart, of Ampion™ in Adults with pain due to osteoarthritis of the knee.
Detailed description
A randomized, placebo-controlled, double-blinded study to evaluate the efficacy and safety of repeated intra-articular injections of Ampion™ in adult subjects with advanced osteoarthritis of the knee. The primary study objective was to evaluate the efficacy and safety from Baseline to Week 20 of 3 Ampion™ 4 mL intra-articular (IA) injections vs saline administered 2 weeks apart in improving knee pain in subjects suffering from osteoarthritis (OA) of the knee (OAK). The secondary study objective was to analyze the effect of Ampion 4 mL vs saline on a change in Patient's Global Assessment (PGA) and knee function from Baseline to Week 20.
Interventions
BIOLOGICAL4 mL injection of Ampion
4 mL injection of Ampion
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
1. Able to provide written informed consent to participate in the study. 2. Willing and able to comply with all study requirements and instructions of the site study staff. 3. Male or female, 40 years to 85 years old (inclusive). 4. Must be ambulatory. 5. Index knee must be symptomatic for greater than 6 months with a clinical diagnosis of OA and supported by radiological evidence (x-ray) acquired at screening and assessed by a central reader. Subjects must have a Kellgren Lawrence Grade of III or IV for inclusion in the study. 6. 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 and confirmed at randomization. 7. Moderate to moderately-severe OA pain in the index knee (even if chronic doses of non-steroidal anti-inflammatory drug \[NSAID\], which have not changed in the 4 weeks prior to screening, have been/are being used). 8. No analgesia taken 24 hours before efficacy measure.
Exclusion criteria
1. As a result of medical review and screening investigation, the Principal Investigator considers the subject unfit for the study. 2. Previous Ampion™ injection in the index knee. 3. Known clinically significant liver abnormality (e.g., cirrhosis, transplant, etc). 4. A history of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin is not an exclusion criterion). 5. A history of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan, sodium caprylate). 6. Presence of tense effusions in the index knee. 7. Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or joint replacement in the index knee, as assessed locally by the Principal Investigator. 8. Isolated patella femoral syndrome, also known as chondromalacia, in the index knee. 9. 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). 10. Major injury to the index knee within the 12 months prior to screening. 11. Severe hip OA ipsilateral to the index knee. 12. 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). 13. Any pharmacological or non-pharmacological treatment targeting OA started or changed during the 4 weeks prior to treatment or likely to be changed during the duration of the study. 14. Use of the following medications are exclusionary: 1. IA injected pain medications in the study knee during the study; 2. 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. Topical treatment on osteoarthritis index knee during the study; 4. Significant anticoagulant therapy (e.g., Heparin or Lovenox) during the study (treatment such as Aspirin and Plavix are allowed); 5. Systemic treatments that may interfere with safety or efficacy assessments during the study; 6. Immunosuppressants; 7. Use of corticosteroids \> 10 mg prednisolone equivalent per day (if ≤ 10 mg prednisolone, the dose must be stable). 15. 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 20 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 20 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 during the months of September, October, and November 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 4 mL intra-articular injection of Ampion
Ampion \<5 kDa ultrafiltrate of 5% human serum albumin | 172 |
| Placebo 4 mL 4 mL placebo intra-articular injection
Placebo: Saline | 170 |
| Total | 342 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 13 | 8 |
Baseline characteristics
| Characteristic | Placebo 4 mL | Total | Ampion 4 mL |
|---|---|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 9.5 | 63.2 years STANDARD_DEVIATION 9.3 | 63.3 years STANDARD_DEVIATION 9.1 |
| BMI (kg/m^2) | 34.9 kg/m^2 STANDARD_DEVIATION 8 | 34.6 kg/m^2 STANDARD_DEVIATION 7.8 | 34.3 kg/m^2 STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 23 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 158 Participants | 319 Participants | 161 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade III | 64 Participants | 114 Participants | 50 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade IV | 106 Participants | 228 Participants | 122 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 58 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 130 Participants | 276 Participants | 146 Participants |
| Region of Enrollment United States | 170 participants | 342 participants | 172 participants |
| Sex: Female, Male Female | 105 Participants | 198 Participants | 93 Participants |
| Sex: Female, Male Male | 65 Participants | 144 Participants | 79 Participants |
| Weight (kg) | 96.4 kg STANDARD_DEVIATION 22.5 | 96.3 kg STANDARD_DEVIATION 23.2 | 96.2 kg STANDARD_DEVIATION 23.8 |
| WOMAC Function | 2.59 score on a scale STANDARD_DEVIATION 0.61 | 2.55 score on a scale STANDARD_DEVIATION 0.62 | 2.51 score on a scale STANDARD_DEVIATION 0.63 |
| WOMAC Pain | 2.57 score on a scale STANDARD_DEVIATION 0.61 | 2.54 score on a scale STANDARD_DEVIATION 0.59 | 2.51 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 / 172 | 1 / 170 |
| other Total, other adverse events | 107 / 172 | 125 / 170 |
| serious Total, serious adverse events | 4 / 172 | 11 / 170 |
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 20 Weeks
Population: Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ampion 4 mL Injection | Change in Knee Pain | -0.96 score on a scale |
| Placebo 4 mL Injection | Change in Knee Pain | -1.10 score on a scale |
p-value: 0.26ANCOVA
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 20 Weeks
Population: Intent to Treat (ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ampion 4 mL Injection | Change in Knee Function | -0.94 score on a scale |
| Placebo 4 mL Injection | Change in Knee Function | -1.08 score on a scale |
p-value: 0.3ANCOVA