Clinical trial NCT05454566: A Study Evaluating the Safety, Tolerability, and Activity of ICM-203 in Subjects With Knee Osteoarthritis.
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_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: 2022-07-12
Enrollment: 18
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: * Group 1: ICM-203 6x10e12 vg
* Group 2: ICM-203 2x10e13 vg
* Group 3: ICM-203 6x10e13 vg
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 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.


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), 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.

Primary outcomes:
measure: Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to Week 52
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
Secondary outcomes:
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:
Study officials:
affiliation: ICM Co. Ltd.
name: Alison Heald, MD
role: STUDY_DIRECTOR
References: