Knee Arthritis, Knee Osteoarthritis, Knee Pain Chronic, Osteoarthritis, Knee
Conditions
Keywords
osteoarthritis, osteoarthritis of the knee, OA, OAK, Kellgren Lawrence (KL)
Brief summary
This is a phase 3 randomized study to confirm the efficacy of an intra-articular injection of Ampion™ in adults with pain due to severe osteoarthritis of the knee.
Detailed description
A Randomized Study to Confirm the Efficacy of an Intra-Articular Injection of Ampion™ in Adults With Pain Due to Severe Osteoarthritis of the Knee There will be a 7-day screening period for each subject followed by a 12-week participation period. The primary trial objective is to evaluate the clinical efficacy of Ampion using the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) (using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) 3.1 Index and Patient's Global Assessment as assessments). The secondary trial objectives are to evaluate the safety of a single intra-articular injection (4 mL) 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; * Must be ambulatory; * Study knee must have a clinical diagnosis of osteoarthritis (OA) supported by radiological evidence (Kellgren Lawrence Grade IV) which is assessed locally (x-rays within the past 6 months of screening are acceptable); * Moderate to moderately-severe OA pain in the study knee (rating of at least 1.5 on the WOMAC A, 5-point Likert Pain Subscale); * Moderate to moderately-severe OA function in the study knee (rating of at least 1.5 on the WOMAC C, 5-point Likert Function Subscale); * WOMAC A, 5-point Likert pain subscale \<1.5 in the contralateral knee; * Ability to discontinue non-steroidal anti-inflammatory drug (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 (81 mg) is allowed during the study); * No analgesia (including acetaminophen) 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 subject 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 study knee for the duration of the trial (e.g. cancer, congenital defects, spine osteoarthritis) * Major injury to the study knee within the 12 months prior to screening * Severe hip osteoarthritis ipsilateral to the study knee * Any pain that could interfere with the assessment of study 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: 1. No intra-articular (IA) injected medications in the study knee during the study (or 12 weeks prior to Baseline). 2. No analgesics containing opioids. 3. NSAIDs are not permitted during the study; acetaminophen is available as a rescue medication during the study from the provided supply. 4. No topical treatment on the study knee during the study 5. No significant anticoagulant therapy (e.g. Heparin or Lovenox) during the study (treatment such as low-dose Aspirin (81 mg) and Plavix are allowed) 6. No systemic treatments that may interfere with safety or efficacy assessments during the study 7. No immunosuppressants 8. No use of systemic or intra-articular 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 |
|---|---|---|
| Number of Participants Classified as Responders | Determined from Baseline to 12 Weeks | Using the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria of WOMAC A Pain subscore, WOMAC C Function subscore, and PGA as composite endpoints. A patient in this study will be considered a responder for the purpose of efficacy analysis if the following criteria are met: (1) demonstration of ≥ 50% improvement AND a 1.0-unit change in pain OR 1.0-unit change in function OR If the patient does not meet this criterion, then the patient must demonstrate at least 2 of the following: * Improvement in pain (WOMAC A) ≥20% and a 0.5 point absolute change in pain from Baseline on the 5-point Likert scale * Improvement in function (WOMAC C) ≥20% and a 0.5 point absolute change in function from Baseline on the 5-point Likert scale * Improvement in patient global assessment (PGA) ≥20% and a 0.5 point absolute change in function from Baseline on the 5-point Likert scale |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ampion 4 mL Dose Ampion (\<5 kilodalton (kDa) ultrafiltrate of 5% Human Serum Albumin (HSA)), solution, 4 mL, single intra-articular injection
Ampion: Ampion (\<5 kilodalton (kDa) ultrafiltrate of 5% HSA) | 144 |
| Saline 4 mL Dose Saline, solution, 4 mL, single intra-articular injection
Saline: 0.9% sodium chloride | 24 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Total | Ampion 4 mL Dose | Saline 4 mL Dose |
|---|---|---|---|
| Age, Continuous | 62.92 years STANDARD_DEVIATION 9.22 | 62.74 years STANDARD_DEVIATION 9.63 | 64.04 years STANDARD_DEVIATION 6.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 5 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 162 Participants | 139 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Patient's Global Assessment (PGA) | 2.8 score on a scale STANDARD_DEVIATION 0.79 | 2.8 score on a scale STANDARD_DEVIATION 0.8 | 2.7 score on a scale STANDARD_DEVIATION 0.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 27 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 1 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 127 Participants | 111 Participants | 16 Participants |
| Region of Enrollment United States | 168 Participants | 144 Participants | 24 Participants |
| Sex: Female, Male Female | 88 Participants | 76 Participants | 12 Participants |
| Sex: Female, Male Male | 80 Participants | 68 Participants | 12 Participants |
| WOMAC Function | 2.6 score on a scale STANDARD_DEVIATION 0.53 | 2.6 score on a scale STANDARD_DEVIATION 0.53 | 2.5 score on a scale STANDARD_DEVIATION 0.53 |
| WOMAC Pain | 2.5 score on a scale STANDARD_DEVIATION 0.55 | 2.5 score on a scale STANDARD_DEVIATION 0.56 | 2.4 score on a scale STANDARD_DEVIATION 0.45 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 144 | 0 / 24 |
| other Total, other adverse events | 52 / 144 | 8 / 24 |
| serious Total, serious adverse events | 0 / 144 | 0 / 24 |
Outcome results
Primary
Number of Participants Classified as Responders
Using the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria of WOMAC A Pain subscore, WOMAC C Function subscore, and PGA as composite endpoints. A patient in this study will be considered a responder for the purpose of efficacy analysis if the following criteria are met: (1) demonstration of ≥ 50% improvement AND a 1.0-unit change in pain OR 1.0-unit change in function OR If the patient does not meet this criterion, then the patient must demonstrate at least 2 of the following: * Improvement in pain (WOMAC A) ≥20% and a 0.5 point absolute change in pain from Baseline on the 5-point Likert scale * Improvement in function (WOMAC C) ≥20% and a 0.5 point absolute change in function from Baseline on the 5-point Likert scale * Improvement in patient global assessment (PGA) ≥20% and a 0.5 point absolute change in function from Baseline on the 5-point Likert scale
Time frame: Determined from Baseline to 12 Weeks
Population: Intent to Treat (ITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ampion 4 mL Dose | Number of Participants Classified as Responders | 102 Participants |
| Saline 4 mL Dose | Number of Participants Classified as Responders | 15 Participants |
Comparison: H0:π ≤ π0 versus HA:π \> π0~Where π0 is the hypothesized clinically significant value for the proportion of responders. The value will be 30% in this study. This test will be tested using an exact binomial test. That is, given the sample size of n, the number of responders X, and the value of π0 =0.30, then probability that X or more events would be observed will be calculated as the p-value. Since this is a one-sided test, the alpha level will be 0.025.p-value: <0.0001Fisher Exact