Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis, osteoarthritis of the knee
Brief summary
Phase 1 will evaluate the safety of 3 intra-articular injections of Ampion™ administered 2 weeks apart to adults with osteoarthritis of the knee. In the absence of serious drug-related Adverse Events (AEs) of unanticipated drug-related AEs, enrollment will be initiated in Phase 2 of the study. Phase 2 will evaluate the efficacy of 3 intra-articular injections, given 2 weeks apart, of Ampion™ in Adults with pain due to osteoarthritis of the knee.
Detailed description
Phase 1: An open-label study to evaluate the safety of 3 intra-articular injections of of Ampion™ 4 mL at Baseline (Day 0) and Weeks 2 and 4 to adults with osteoarthritis (OA) knee pain. Enrollment will be initiated in Phase 2 if no serious drug-related adverse events or unanticipated drug-related adverse events are observed. Phase 2: A randomized, placebo-controlled, double-blind, study to evaluate the safety and efficacy of 3 intra-articular (IA) injections of Ampion™ 4 mL at Baseline (Day 0) and Weeks 2 and 4 in adults with OA knee pain. Study Objectives Phase 1: To evaluate the safety of Ampion™ 4 mL administered as 3 intra-articular injections, two weeks apart, in subjects suffering from OA of the knee from Baseline to Week 20. Phase 2: The primary study objective is to evaluate the safety and efficacy of Ampion™ 4 mL versus placebo injection from Baseline to Week 20, when administered as three intra-articular (IA) injections (at Baseline (Day 0) and Weeks 2 and 4), in improving knee pain in subjects suffering from OA of the knee.
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. Ambulatory 5. Index knee must have been symptomatic for greater than 6 months with a clinical diagnosis of OA and supported by radiological evidence (Kellgren Lawrence Grade II-IV) acquired at Screening 6. Moderate to moderately severe OA pain in the index knee (rating of at least 1.5 on the WOMAC 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 nonsteroidal anti-inflammatory drugs \[NSAIDs\], which have not changed in the 4 weeks prior to Screening, had been 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 considered the subject unfit for the study 2. Previous Ampion injection 3. Known clinically significant liver abnormality (eg, cirrhosis, transplant, etc.) 4. History of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin was not an exclusion criterion) 5. 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 (eg, 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 (eg, 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 any of the following medications: * IA-injected pain medications in the index knee during the study * Analgesics containing opioids (NSAIDs were allowed at the levels preceding the study and acetaminophen was available as rescue medication during the study from the provided supply) * Topical prescription treatment on the index knee during the study * Significant anticoagulant therapy (eg, heparin or enoxaparin) during the study (aspirin and clopidogrel were allowed) * Systemic treatments that could interfere with safety or efficacy assessments during the study * Immunosuppressants * Corticosteroids \>10 mg prednisolone equivalent per day or corticosteroids at doses ≤10 mg prednisolone equivalent that had been changed during the study 15. Any human albumin treatment in the 3 months before randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Adverse Events and Serious Adverse Events (Phase 1) | 24 Weeks | Incidence and severity of adverse events and serious adverse events evaluated at 24 weeks |
| Change in Knee Pain (Phase 2) | 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 (Phase 2) | 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 for Phase 1 occurred in June and July 2014. Recruitment for Phase 2 occurred in medical clinics during the months of August, September, and October 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 |
|---|---|
| Phase 1 - Ampion 4 mL Injection Non-Randomized; 4 mL Intra-articular injection of Ampion | 7 |
| Phase 2 - Ampion 4 mL Injection 4 mL Intra-articular injection of Ampion | 20 |
| Phase 2 - Placebo 4 mL Injection 4 mL placebo intra-articular injection
Placebo: Saline | 20 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase 2 20 Week Efficacy | Protocol Violation | 0 | 1 |
| Phase 2 20 Week Efficacy | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Phase 1 - Ampion 4 mL Injection | Phase 2 - Ampion 4 mL Injection | Phase 2 - Placebo 4 mL Injection | Total |
|---|---|---|---|---|
| Age, Continuous | 65.1 Years STANDARD_DEVIATION 9.8 | 63.7 Years STANDARD_DEVIATION 10.3 | 61.4 Years STANDARD_DEVIATION 9.4 | 62.9 Years STANDARD_DEVIATION 9.8 |
| BMI | 27.2 lbs/in^2 STANDARD_DEVIATION 4.6 | 29.8 lbs/in^2 STANDARD_DEVIATION 5.1 | 29.9 lbs/in^2 STANDARD_DEVIATION 4.9 | 29.5 lbs/in^2 STANDARD_DEVIATION 4.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 18 Participants | 19 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade II | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade III | 4 Participants | 11 Participants | 12 Participants | 27 Participants |
| Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade IV | 3 Participants | 7 Participants | 8 Participants | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 17 Participants | 20 Participants | 44 Participants |
| Region of Enrollment United States | 7 participants | 20 participants | 20 participants | 47 participants |
| Sex: Female, Male Female | 1 Participants | 12 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 7 Participants | 21 Participants |
| Weight | 188.9 Pounds STANDARD_DEVIATION 35.2 | 197.6 Pounds STANDARD_DEVIATION 44.7 | 193.8 Pounds STANDARD_DEVIATION 44.4 | 194.7 Pounds STANDARD_DEVIATION 42.5 |
| WOMAC Function | — | 2.17 score on a scale STANDARD_DEVIATION 0.5 | 2.30 score on a scale STANDARD_DEVIATION 0.52 | 2.24 score on a scale STANDARD_DEVIATION 0.51 |
| WOMAC Pain | — | 2.23 score on a scale STANDARD_DEVIATION 0.47 | 2.17 score on a scale STANDARD_DEVIATION 0.44 | 2.21 score on a scale STANDARD_DEVIATION 0.46 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 6 / 7 | 19 / 20 | 16 / 20 |
| serious Total, serious adverse events | 0 / 7 | 3 / 20 | 0 / 20 |
Outcome results
Primary
Change in Knee Pain (Phase 2)
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) | Dispersion |
|---|---|---|---|
| Phase 1 - Ampion 4 mL Injection | Change in Knee Pain (Phase 2) | -1.41 score on a scale | Standard Deviation 0.81 |
| Placebo 4 mL Injection | Change in Knee Pain (Phase 2) | -0.85 score on a scale | Standard Deviation 0.64 |
p-value: 0.02t-test, 2 sided
Primary
Incidence and Severity of Adverse Events and Serious Adverse Events (Phase 1)
Incidence and severity of adverse events and serious adverse events evaluated at 24 weeks
Time frame: 24 Weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1 - Ampion 4 mL Injection | Incidence and Severity of Adverse Events and Serious Adverse Events (Phase 1) | Serious Adverse Event | 0 events |
| Phase 1 - Ampion 4 mL Injection | Incidence and Severity of Adverse Events and Serious Adverse Events (Phase 1) | Any Adverse Event | 15 events |
Secondary
Change in Knee Function (Phase 2)
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) | Dispersion |
|---|---|---|---|
| Phase 1 - Ampion 4 mL Injection | Change in Knee Function (Phase 2) | -1.27 score on a scale | Standard Deviation 0.81 |
| Placebo 4 mL Injection | Change in Knee Function (Phase 2) | -0.98 score on a scale | Standard Deviation 0.69 |
p-value: 0.25t-test, 2 sided