Efficacy and Safety of AqueousJoint Intra-Articular Injections in Mild to Moderate Knee Osteoarthritis

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate the Efficacy and Safety of AqueousJoint Intra-Articular Injection in Mild to Moderate Knee Osteoarthritis of AqueousJoint. The main questions it aims to answer are: To demonstrate superior efficacy of AqueousJoint administered via intra-articular injection versus placebo during the study period. To evaluate the efficacy of two different concentrations of AqueousJoint, administered via single IA injection as compared to control group (placebo) One IA injection of AqueousJoint or Placebo will be injected to participants' knee. Follow up will take place up to six months.

Detailed Description
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This study aims to assess the efficacy and safety of intra-articular injection of Aqueous Joint at two different concentrations administered via a single injection in osteoarthritic patients up to 26 weeks of follow-up in a double-blind, randomized clinical study. Primary Efficacy Objective The primary objective is to demonstrate the superior efficacy of AqueousJoint administered via intra-articular injection versus placebo during the study period in terms of pain reduction. Pain and functional outcomes will be assessed using VAS and KOOS at each FU visit (up to and including 12 weeks) and compared to the baseline levels. Secondary Efficacy Objective The secondary objective is to assess changes from baseline to 26 weeks in KOOS Pain, symptoms, QOL, ADL and sport subscores. Change from Baseline in Patient's Global Assessment (PGA) and Evaluators' Global Assessment (EGA) of Osteoarthritis at Week 26 will be evaluated. Safety Objectives Safety will be evaluated by the occurrence of Adverse Events during the study. Adverse Events will be reported in terms of incidence, severity, and frequency of all Adverse Events (AE).

Official Title
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Efficacy and Safety of AqueousJoint Intra-Articular Injections in Mild to Moderate Knee Osteoarthritis: Prospective, Placebo Controlled, Randomized, Double-Blinded Study

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: AqueousJoint


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has signed and dated the informed consent form Age ≥30 and ≤ 85 years old Pain in the intended study knee with an average VAS score (active) of ≥3 over the last week before screening. Degenerative changes in the intended study knee that can be categorized as grade I -III- Kellgren Lawrence based upon standing anterior- posterior and lateral radiographsof the knee Body Mass Index (BMI) between 18.5 and 38 A negative urine pregnancy test female patient with childbearing potential at Visit 1 prior to intra-articular injection of AqueousJoint. If female, the subject must be either postmenopausal, OR permanently surgically sterile OR for women of childbearing potential using at least 2 methods of birth control that are effective from at least 30 days before Visit 1 through visit 26w (26 weeks post injection). Are willing or able to comply with procedures required in this protocol. Exclusion Criteria: Osteoarthritis of the index knee graded 4 according to the Kellgren-Lawrence Grading History of significant knee trauma or previous surgery of the intended study knee within the last 3 months preceding the screening Pain in both knees with a VAS score of ≥5 Intra-articular injection to the intended study knee within 3 months before Screening Significant instability of the index knee Malalignment more than 10 degrees varus OR 10 degrees valgus according to standing X-ray Intake of chronic pain medications (especially opioid pain relievers) without an option to pause for the period of the study History of Psoriatic Arthritis, Rheumatoid Arthritis, or any other inflammatory condition associated with arthritis Wound in the area of the intended study knee Any known tumor of the index knee Any known history of intra-articular or osseous infection of the index knee Any evidence of active infection anywhere in the body. Urinary Tract Infection (UTI) patients can be included following antibiotic treatment, provided that two consecutive cultures are negative (taken within at least 2 weeks of each other) Any known history of inflammatory arthropathy or crystal-deposition arthropathy Any known systemic cartilage and/or bone disorder, such as but not limited to, chondrodysplasia or osteogenesis imperfecta Body Mass Index (BMI) > 38 Active malignances, excluding BCC. Chemotherapy and/or radiation in the past 12 months Known history of a severe allergic reaction Patient who is pregnant or intends to become pregnant during the study History of any significant systemic disease, such as but not limited to: HIV, hepatitis, HTLV, syphilis, and coagulopathies A Known substance or alcohol abuse Participation in other clinical trials within 60 days to before the study or concurrent with the study Known insulin dependent diabetes mellitus Unable to undergo X-ray

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1 (Control)<br>1 IA injection of 4 ml Normal Saline solution. | Device: AqueousJoint<br>* AqueousJoint is a new intra-articular (IA) injectable joint lubricant for patients suffering from joint pain developed by Liposphere LTD. AqueousJoint is a liposomal boundary lubricant which coats the cartilage surface and protects it from further damage and degradation.<br>|
| Experimental: Group 2 (Study)<br>1 IA injection of 4 ml AqueousJoint low conc (15mM) | Device: AqueousJoint<br>* AqueousJoint is a new intra-articular (IA) injectable joint lubricant for patients suffering from joint pain developed by Liposphere LTD. AqueousJoint is a liposomal boundary lubricant which coats the cartilage surface and protects it from further damage and degradation.<br>|
| Experimental: Group 3 (Study)<br>1 IA injection of 4 ml AqueousJoint high conc (30mM) | Device: AqueousJoint<br>* AqueousJoint is a new intra-articular (IA) injectable joint lubricant for patients suffering from joint pain developed by Liposphere LTD. AqueousJoint is a liposomal boundary lubricant which coats the cartilage surface and protects it from further damage and degradation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Endpoint | Change in pain score by VAS. VAS score is between 0 to 10, which higher score means worse pain (worse pain). | Baseline up to 12 weeks | 
| Efficacy Endpoint | Change in KOOS over the course of the 12-week initial treatment period as measured by participants using the Knee injury and Osteoarthritis Outcome Score (KOOS). KOOS score is between 0 to 100 - higher score means better outcome. | Day 0, up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in KOOS sub scores | Change in KOOS Symptoms/ Sport / ADL / QOL sub score. KOOS score is between 0 to 100 - higher score means better outcome. | Baseline to 26 weeks | 
| Overall KOOS | Overall KOOS responder rate. KOOS score is between 0 to 100 - higher score means better outcome. | Baseline to 26 weeks | 
| PGA/EGA | Change in Patient's / Evaluators' Global Assessment (PGA/EGA). PGA/ EGA assessment includes 5 options to answer - between 1 to 5 - which 1 means 'very good' , and 5 means 'very poor'. | Baseline to 26 weeks | 
| Safety Endpoint | Adverse events, including serious adverse events | Baseline to 26 weeks |