A Study Evaluating the Safety, Tolerability, and Activity of ICM-203 in Subjects With Knee Osteoarthritis.

A Single Dose Escalation Study of Intra-Articular ICM-203 in Subjects With Kellgren-Lawrence Grade 2 or Grade 3 Osteoarthritis of the Knee

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 into the knee of subjects with mild to moderate knee osteoarthritis (OA).

Approximately 6 to 18 subjects will be enrolled into 3 successive dose-escalating groups in a 3+3 study design, whereby 3 study subjects in each group will be dosed sequentially with ICM-203 and 3 additional subjects will be dosed at the same dose level if a dose limiting toxicity (DLT) occurs in any of the first 3 subjects.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Genetic: ICM-203

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Alison Heald, MD; Phone Number: +1 206 465 3912; Email: alison.heald@icm-bio.com
• Study Contact Backup: Name: Youngna Yum, PhD; Phone Number: +82 2 324 8534; Email: youngna.yum@icm-bio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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), at the time of screening.
4. KOOS function in daily living score >25, a measure of knee function ranging from 0 (extreme problems) to 100 (no problems), at the time of screening .
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 or psychiatric condition that, in the opinion of the Investigator, would make the subject unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: ICM-203 (Low dose); 3 to 6 subjects will receive a single intra-articular injection of ICM-203 at 6x10e12 vg into the target knee at Day 1	Genetic: ICM-203; Intra-articular injection
Experimental: Group 2: ICM-203 (Medium dose); 3 to 6 subjects will receive a single intra-articular injection of ICM-203 at 2x10e13 vg into the target knee at Day 1	Genetic: ICM-203; Intra-articular injection
Experimental: Group 3: ICM-203 (High dose); 3 to 6 subjects will receive a single intra-articular injection of ICM-203 at 6x10e13 vg into the target knee at Day 1	Genetic: ICM-203; Intra-articular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee pain	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)	Up to Week 52
Analgesic use	Evaluation of change from baseline in in use of analgesics, such as acetaminophen and NSAIDs	Up to Week 52
Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS)	Evaluation of change from baseline in MOAKS, focusing on articular cartilage and effusion-synovitis	Up to Week 52
Joint space width	Evaluation of change from baseline in Joint space width in mm as measured on knee radiograph	Up to Week 52
Treatment-Emergent Adverse Events (TEAEs)	Incidence and Severity of Treatment-Emergent Adverse Events following administration of study drug	Up to Week 52
Knee function	Evaluation of change from baseline in knee function as measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS) function in daily living subscale ranging from 0 (extreme problems) to 100 (no problems)	Up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Humoral response to AAV5.2 capsid	Evaluation of change from baseline in neutralizing antibody titers against AAV5.2 in serum	Up to Week 52
Cellular immune response to AAV5.2 capsid	Evaluation of change from baseline in T-cell responses to AAV5.2 capsid	Up to Week 52
Systemic biodistribution of ICM-203	Evaluation of presence of ICM-203 in peripheral blood after administration of study drug	Up to Week 52

Collaborators and Investigators

• Sponsor: ICM Co. Ltd.
• Investigators: Study Director: Alison Heald, MD, ICM Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): November 15, 2026
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): November 15, 2028

Study Registration Dates

• First Submitted: July 4, 2022
• First Submitted That Met QC Criteria: July 7, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: osteoarthritis; gene therapy; adeno-associated virus; ICM-203
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: ICM 20-1003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No