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

Osteoarthritis, Knee Clinical Trial

Official title:

A Phase 1/2a, Double-Blind, Placebo-Controlled 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: Recruiting

Administrative data

• NCT number: NCT04875754
• Other study ID #: ICM 20-1001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 17, 2022
• Est. completion date: December 2024

Study information

• Verified date: August 2023
• Source: ICM Co. Ltd.
• Contact: Yoenhee Ahn
• Phone: +82 2 324 8550
• Email: yoenhee.ahn[@]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 or matching placebo into the knee of subjects with mild to moderate knee osteoarthritis (OA).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: December 2024
• Est. primary completion date: March 2024
• 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).

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.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Genetic:
• ICM-203
Intra-articular injection

Drug:
• Placebo
Intra-articular injection

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Barwon Health	Geelong	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
ICM Biotech Australia Pty Ltd.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-Emergent Adverse Events (TEAEs)	Incidence of Treatment-Emergent Adverse Events following administration of study drug	Up to Week 52
Primary	Severity of Treatment-Emergent Adverse Events (TEAEs)	Severity of Treatment-Emergent Adverse Events graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0, following administration of study drug	Up to Week 52
Secondary	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
Secondary	Knee function	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)	Up to Week 52
Secondary	Analgesic use	Evaluation of change from baseline in in use of analgesics, such as acetaminophen and NSAIDs	Up to Week 52
Secondary	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
Secondary	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