Osteoarthritis, Knee
Conditions
Keywords
adeno-associated virus, gene therapy, ICM-203, osteoarthritis
Brief summary
The purpose of this study is to determine the safety, tolerability, and activity of ICM-203, a recombinant adeno-associated viral (AAV) vector that expresses a therapeutic gene that promotes cartilage formation, reduces joint inflammation and pain, as well as improves joint physical function, by injecting escalating doses of ICM-203 or matching placebo into the knee of subjects with mild to moderate knee osteoarthritis (OA).
Interventions
GENETICICM-203
Intra-articular injection
DRUGPlacebo
Intra-articular injection
Sponsors
ICM Biotech Australia Pty Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
* Group 1: ICM-203 6x10e12 vg or Placebo * Group 2: ICM-203 2x10e13 vg or Placebo * Group 3: ICM-203 6x10e13 vg or Placebo (Optional)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Body Mass Index (BMI) of 18.0 to 40.0 kg/m2, inclusive, at the time of screening. 2. Kellgren-Lawrence grade 2 or grade 3 OA of target knee. 3. Target knee pain between 4 and 9, inclusive, on an NRS ranging from 0 (no pain) to 10 (worst pain imaginable). 4. KOOS function in daily living score \>25, a measure of knee function ranging from 0 (extreme problems) to 100 (no problems). 5. A stable treatment regimen for symptomatic relief of OA, including NSAIDs, for 4 weeks prior to screening.
Exclusion criteria
1. History of rheumatoid arthritis, psoriatic arthritis, gout, pseudogout, autoimmune OA, chondrocalcinosis, hemochromatosis, villonodular synovitis, and synovial chondromatosis or other disorder that in the opinion of the Investigator could cause inflammation of the knee. 2. Injection of steroid, hyaluronate or other agent, into the target knee less than 90 days prior to day 1. 3. Major injury to the target knee, such as torn ligament or severe sprain, within 12 months of screening. 4. Disability so severe that the subject cannot comply with the study requirements, including knee symptoms that result in significant difficulty or inability to walk. 5. Surgery on the target knee within 180 days prior to day 1 6. Total knee arthroplasty or other knee surgery planned in the next 12 months. 7. Active joint infection or other concurrent medical (diabetes, uncontrolled hypertension, severe osteoporosis, glaucoma) or psychiatric condition that, in the opinion of the Investigator, would make the subject unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Events (TEAEs) | Up to Week 52 | Incidence of Treatment-Emergent Adverse Events following administration of study drug |
| Severity of Treatment-Emergent Adverse Events (TEAEs) | Up to Week 52 | Severity of Treatment-Emergent Adverse Events graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0, following administration of study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Knee pain | Up to Week 52 | Evaluation of change from baseline in knee pain as measured using a Numerical Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable) |
| Knee function | Up to Week 52 | Evaluation of change from baseline in knee function as measured using the Function in Daily Living subscore of the Knee Injury and Osteoarthritis Outcome Score (KOOS) |
| Analgesic use | Up to Week 52 | Evaluation of change from baseline in in use of analgesics, such as acetaminophen and NSAIDs |
| Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) | Up to Week 52 | Evaluation of change from baseline in MOAKS, focusing on bone marrow lesions, articular cartilage, and effusion-synovitis |
| Joint space width | Up to Week 52 | Evaluation of change from baseline in Joint space width in mm as measured on knee radiograph |
| Humoral response to AAV5.2 capsid | Up to Week 52 | Evaluation of change from baseline in neutralizing antibody titers against AAV5.2 in serum |
| Cellular immune response to AAV5.2 capsid | Up to Week 52 | Evaluation of change from baseline in T-cell responses to AAV5.2 capsid |
| Systemic biodistribution of ICM-203 | Up to Week 52 | Evaluation of presence of ICM-203 in peripheral blood after administration of study drug |
Countries
Australia
Contacts
STUDY_DIRECTORAlison Heald, MD
ICM Co. Ltd.
Outcome results
None listed