Clinical trial NCT04875754: A Study Evaluating the Safety, Tolerability, and Range of Biologically Active Doses of ICM-203 in Mild to Moderate Knee Osteoarthritis
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Osteoarthritis, Knee
Keywords: adeno-associated virus
gene therapy
ICM-203
osteoarthritis
Lead sponsor: ICM Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2021-05-06
Enrollment: 16
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: * Group 1: ICM-203 6x10e12 vg or Placebo
* Group 2: ICM-203 2x10e13 vg or Placebo
* Group 3: ICM-203 6x10e13 vg or Placebo (Optional)
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to Week 52
measure: Severity of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to Week 52
Secondary outcomes:
measure: Knee pain
timeFrame: Up to Week 52
measure: Knee function
timeFrame: Up to Week 52
measure: Analgesic use
timeFrame: Up to Week 52
measure: Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS)
timeFrame: Up to Week 52
measure: Joint space width
timeFrame: Up to Week 52
measure: Humoral response to AAV5.2 capsid
timeFrame: Up to Week 52
measure: Cellular immune response to AAV5.2 capsid
timeFrame: Up to Week 52
measure: Systemic biodistribution of ICM-203
timeFrame: Up to Week 52
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Geelong
country: Australia
facility: Barwon Health
state: Victoria
Study officials:
affiliation: ICM Co. Ltd.
name: Alison Heald, MD
role: STUDY_DIRECTOR
References: