A Study to Evaluate Safety of Three Intra-articular Injections of Ampion in the Knee of Adults With Osteoarthritis Pain

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.

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)
• Ambulatory
• 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
• 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
• 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)
• No analgesia taken 24 hours before efficacy measure

Exclusion criteria

• As a result of medical review and screening investigation, the Principal Investigator considered the subject unfit for the study
• Previous Ampion injection
• Known clinically significant liver abnormality (eg, cirrhosis, transplant, etc.)
• History of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin was not an exclusion criterion)
• History of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan, sodium caprylate)
• Presence of tense effusions in the index knee
• Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or joint replacement in the index knee, as assessed locally by the Principal Investigator
• Isolated patella femoral syndrome, also known as chondromalacia in the index knee
• 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)
• Major injury to the index knee within the 12 months prior to Screening
• Severe hip OA ipsilateral to the index knee
• 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)
• 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
• 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
• Any human albumin treatment in the 3 months before randomization