An Efficacy and Safety Study of Two Doses of Intra-Articular Ampion Injection for Pain of Osteoarthritis of the Knee

Phase 2

Completed

Conditions: Osteoarthritis of the Knee

Interventions: Biological: 4 mL injection of Ampion
Drug: 10 mL Injection of Placebo
Drug: 4 mL Injection of Placebo
Biological: 10 mL Injection of Ampion

Registration Number: NCT01839331

Lead Sponsor: Ampio Pharmaceuticals. Inc.

Brief Summary: This study will evaluate the efficacy of two doses of Intra-Articular Injection of Ampion™ in Adults with pain due to osteoarthritis of the knee.

Detailed Description: A Randomized, Placebo-controlled, Double-Blind Study to Evaluate the Efficacy and Safety of two Doses of Intra-Articular Injection of Ampion™ in Adults with pain due to osteoarthritis of the knee.

The primary trial objective is to evaluate whether there is greater efficacy of 10 mL Ampion™ versus 10 mL placebo than 4 mL Ampion™ versus 4 mL placebo intra-articular (IA) injection in improving knee pain, when applied to patients suffering from OA of the knee.

The secondary trial objective include: the evaluation of the safety of an intra-articular injection of Ampion™ when applied to patients suffering from OA of the knee, evaluation of the efficacy of intra-articular injection of Ampion™ and placebo on stiffness and function when applied to patients suffering from OA of the knee and evaluation of responder status defined by the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) Criteria.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 329

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)
Must be ambulatory
Index knee must be symptomatic for greater than 6 months with a clinical diagnosis of osteoarthritis (OA) and supported by radiological evidence Kellgren Lawrence Grade II to IV) that is not older than 6 months prior to the date of screening
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
Moderate to moderately-severe OA pain in the index knee (even if chronic doses of nonsteroidal anti-inflammatory drug (NSAID), which have not changed in the 4 weeks prior to screening, have been/are being used)
No analgesia (including acetaminophen [paracetamol]) taken 12 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 patient 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 index knee for the duration of the trial e.g. 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 (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
Use of the following medications:
1. No IA injected pain medications in the study knee during the study
2. No 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. No topical treatment on osteoarthritis index knee during the study
4. No significant anticoagulant therapy (e.g. Heparin or Lovenox) during the study (treatment such as Aspirin and Plavix are allowed)
5. No systemic treatments that may interfere with safety or efficacy assessments during the study
6. No immunosuppressants
7. No use of corticosteroids > 10 mg prednisolone equivalent per day (if ≤ 10 mg prednisolone, the dose must be stable)
Any human albumin treatment in the 3 months before randomization

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ampion 4 mL Dose	4 mL injection of Ampion	4 mL Injection of Ampion
Placebo 10 mL Dose	10 mL Injection of Placebo	10 mL Injection of Placebo
Placebo 4 mL Dose	4 mL Injection of Placebo	4 mL Injection of Placebo
Ampion 10 mL Dose	10 mL Injection of Ampion	10 mL Injection of Ampion

Primary Outcome Measures

Name	Time	Method
Change in Knee Pain	Scored at Baseline and 12 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 Outcome Measures

Name	Time	Method
Change in Knee Function	Scored at Baseline and 12 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.
Change in Knee Stiffness.	Scored at Baseline and 12 weeks.	Mean Change in WOMAC B stiffness score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a reduction in stiffness.
Change in Patient's Global Assessment	Scored at Baseline and 12 weeks.	Patients are asked the following question: "Considering all the ways in which your arthritis affects you, please indicate how you are doing." 5-point Likert scale (0 = very well, 1 = well, 2 = fair, 3 = poor, 4 = very poor). A negative value constitutes an improvement in patient's assessment of disease severity.