Severe Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis, osteoarthritis of the knee
Brief summary
This Open Label Extension (OLE) study will assess the safety of long-term treatment with a 4 mL intra-articular injection of Ampion™ in adults with pain due to severe osteoarthritis of the knee
Detailed description
An Open Label Extension (OLE) study will assess the safety of long-term treatment with a 4 mL intra-articular injection of Ampion™ in adults with pain due to severe osteoarthritis of the knee. The primary trial objective was to evaluate the safety of a 4-mL intra-articular (IA) injection of Ampion with repeat dosing every 12 weeks for 52 weeks with five total injections of Ampion.
Interventions
BIOLOGICAL4 mL injection of AMPION™
4 mL injection of AMPION™
Sponsors
Ampio Pharmaceuticals. Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open Label
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects who completed the AP-003-C Main study and have not developed any exclusionary criteria 2. Able to provide written informed consent to participate in the study 3. Willing and able to comply with all study requirements and instructions of the site study staff 4. Male or female, 40 years to 85 years old (inclusive), as assessed in the AP-003-C Main Study 5. Must be ambulatory, as assessed in the AP-003-C Main Study 6. Study knee must have a clinical diagnosis of OA and supported by radiological evidence (Kellgren Lawrence Grade IV) as assessed in the AP-003-C Main Study. 7. Moderate to moderately-severe OA pain in the study knee (rating of at least 1.5 on the WOMAC Index 3.1 5-point Likert Pain Subscale), as assessed in the AP-003-C Main Study 8. Moderate to moderately-severe OA function in the study knee (rating of at least 1.5 on the WOMAC Index 3.1 5-point Likert Function Subscale), as assessed in the AP-003-C Main Study 9. WOMAC A, 5-point Likert pain subscale \<1.5 in the contralateral knee, as assessed in the AP-003-C Main Study 10. Ability to discontinue NSAID ± 72 hours before/after injections (in-office visits). Low-dose Aspirin (81 mg) is allowed during the study but must not be taken at least 24 hours prior to in-office visits. 11. No analgesia (including acetaminophen \[paracetamol\]) taken 24 hours prior to an efficacy measure
Exclusion criteria
1. As a result of medical review and screening investigation, the Principal Investigator considers the patient unfit for the study 2. Known clinically significant liver abnormality (e.g., cirrhosis, transplant, etc.) 3. A history of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin is not an exclusion criterion) 4. A history of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan, sodium caprylate) 5. Presence of tense effusions 6. Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or joint replacement in the affected knee 7. Isolated patella femoral syndrome, also known as chondromalacia 8. 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) 9. Major injury to the index knee within the last 12 months 10. Severe hip osteoarthritis ipsilateral to the index knee 11. 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) 12. Any pharmacological or non-pharmacological treatment targeting OA started or changed 4 weeks prior to entry into the OLE study, or likely to be changed during the duration of the OLE study 13. Pregnancy or planning to become pregnant during the study 14. Use of the following medications: 1. No IA injected pain medications in the study knee during the study. No Hyaluronic Acid (HA) or steroid injections in the study knee at least 12 weeks prior to Day 84 of the Extension Study. HA and steroid injections in the contralateral knee (non-study knee) are acceptable while on study except ± 14 days of an Ampion injection in the study knee. 2. No analgesics containing opioids 3. NSAIDs are not permitted ± 72 hours before/after injections at in-office visits; 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 Aspirin 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 corticosteroids 9. No human albumin treatment in the 3 months prior to the AP-003-C Main Study or interim period prior to enrollment into the OLE study. No human albumin treatment throughout the duration of the OLE study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) | 52 weeks | Incidence and severity of treatment emergent adverse events (TEAEs) evaluated up to 52 weeks, including the 12 weeks in the Main study AP-003-C (NCT03182686). |
Countries
United States
Participant flow
Recruitment details
Subjects who had completed clinical trial AP-003C were eligible to enroll in the open label extension study. All subjects were assigned to the Ampion treatment group.
Pre-assignment details
No pharmacological or non-pharmacological treatment targeting osteoarthritis (OA) started or changed 4 weeks prior to entry into the study, or likely to be changed during the duration of the study
Participants by arm
| Arm | Count |
|---|---|
| Ampion 4 mL Dose 4 mL Ampion (\<5 kilodalton (kDa) ultrafiltrate of 5% Human Serum Albumin (HSA)), solution | 94 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other | 2 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Sponsor Terminated Study | 75 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Ampion 4 mL Dose |
|---|---|
| Age, Continuous | 63.3 Years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 66 Participants |
| Region of Enrollment United States | 94 participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 94 |
| other Total, other adverse events | 22 / 94 |
| serious Total, serious adverse events | 0 / 94 |
Outcome results
Primary
Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)
Incidence and severity of treatment emergent adverse events (TEAEs) evaluated up to 52 weeks, including the 12 weeks in the Main study AP-003-C (NCT03182686).
Time frame: 52 weeks
Population: Intent To Treat (ITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ampion 4 mL Dose | Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) | Mild treatment-emergent adverse event (TEAE) | 21 Events |
| Ampion 4 mL Dose | Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) | Moderate treatment-emergent adverse event (TEAE) | 11 Events |
| Ampion 4 mL Dose | Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) | Severe treatment-emergent adverse event (TEAE) | 2 Events |