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

Osteoarthritis, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05454566
• Other study ID #: ICM 20-1003
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: November 15, 2024
• Est. completion date: November 2026

Study information

• Verified date: March 2024
• Source: ICM Co. Ltd.
• Contact: Alison Heald, MD
• Phone: +1 206 465 3912
• Email: alison.heald[@]icm-bio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: November 2026
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Genetic:
• ICM-203
Intra-articular injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ICM Co. Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-Emergent Adverse Events (TEAEs)	Incidence and Severity of Treatment-Emergent Adverse Events following administration of study drug	Up to Week 52
Primary	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
Primary	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
Primary	Analgesic use	Evaluation of change from baseline in in use of analgesics, such as acetaminophen and NSAIDs	Up to Week 52
Primary	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
Primary	Joint space width	Evaluation of change from baseline in Joint space width in mm as measured on knee radiograph	Up to Week 52
Secondary	Humoral response to AAV5.2 capsid	Evaluation of change from baseline in neutralizing antibody titers against AAV5.2 in serum	Up to Week 52
Secondary	Cellular immune response to AAV5.2 capsid	Evaluation of change from baseline in T-cell responses to AAV5.2 capsid	Up to Week 52
Secondary	Systemic biodistribution of ICM-203	Evaluation of presence of ICM-203 in peripheral blood after administration of study drug	Up to Week 52