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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Placebo; Genetic: ICM-203

• Study Type: Interventional
• Enrollment (Estimated): 16
• 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: Yoenhee Ahn; Phone Number: +82 2 324 8550; Email: yoenhee.ahn@icm-bio.com

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
      • Contact: Lucian Bogdan Solomon, MD
      • Principal Investigator: Lucian Bogdan Solomon, MD
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Recruiting
      • Barwon Health
      • Contact: Richard Page, MD
      • Principal Investigator: Richard Page, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 78 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).
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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: ICM-203 (Low dose) vs 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	Drug: Placebo; Intra-articular injection; Genetic: ICM-203; Intra-articular injection
Experimental: Group 2: ICM-203 (Medium dose) vs 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	Drug: Placebo; Intra-articular injection; Genetic: ICM-203; Intra-articular injection
Experimental: Group 3: ICM-203 (High dose) vs Placebo (Optional); 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	Drug: Placebo; Intra-articular injection; Genetic: ICM-203; Intra-articular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Adverse Events (TEAEs)	Incidence of Treatment-Emergent Adverse Events following administration of study drug	Up to Week 52
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 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
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
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
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 Biotech Australia Pty Ltd.
• Investigators: Study Director: Alison Heald, MD, ICM Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2022
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: May 3, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: osteoarthritis; gene therapy; adeno-associated virus; ICM-203
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: ICM 20-1001

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