A Study Evaluating the Safety, Tolerability, and Range of Biologically Active Doses of ICM-203 in Mild to Moderate Knee Osteoarthritis

Phase 1

Active, not recruiting

• Conditions: Osteoarthritis, Knee
• Interventions: Genetic: ICM-203; Drug: Placebo

• Registration Number: NCT04875754
• Lead Sponsor: ICM Biotech Australia Pty Ltd.

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-04-26
• Study First Submitted QC: 2021-05-03
• Study First Posted: 2021-05-06
• Study Start: 2022-03-17
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-01
• Primary Completion: 2026-03
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 16

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group 1: ICM-203 (Low dose) vs Placebo	ICM-203	8 subjects will be randomized to receive a single intra-articular injection of ICM-203 at 6x10e12 vg (n=6) or placebo (n=2) into the target knee at Day 1
Group 1: ICM-203 (Low dose) vs Placebo	Placebo	8 subjects will be randomized to receive a single intra-articular injection of ICM-203 at 6x10e12 vg (n=6) or placebo (n=2) into the target knee at Day 1
Group 2: ICM-203 (Medium dose) vs Placebo	ICM-203	4 subjects will be randomized to receive a single intra-articular injection of ICM-203 at 2x10e13 vg (n=3) or placebo (n=1) into the target knee at Day 1
Group 2: ICM-203 (Medium dose) vs Placebo	Placebo	4 subjects will be randomized to receive a single intra-articular injection of ICM-203 at 2x10e13 vg (n=3) or placebo (n=1) into the target knee at Day 1
Group 3: ICM-203 (High dose) vs Placebo (Optional)	ICM-203	4 subjects will be randomized to receive a single intra-articular injection of ICM-203 at 6x10e13 vg (n=3) or placebo (n=1) into the target knee at Day 1
Group 3: ICM-203 (High dose) vs Placebo (Optional)	Placebo	4 subjects will be randomized to receive a single intra-articular injection of ICM-203 at 6x10e13 vg (n=3) or placebo (n=1) into the target knee at Day 1

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (2)

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Barwon Health; 🇦🇺 Geelong, Victoria, Australia