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

• Status: Not yet recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the safety, tolerability, and activity of increasing doses of ICM-203 injected into the knee of subjects with mild to moderate knee osteoarthritis.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ICM Co. Ltd.

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. Total WOMAC score ≤70 for target knee, on a scale ranging from 0 to 96 where a higher score indicates worse pain, stiffness, and functional limitations.

5. A stable treatment regimen for symptomatic relief of OA, including NSAIDs, for 4 weeks prior to screening.

6. Female subjects of child-bearing potential, with a fertile male sexual partner, must use a highly effective method of contraception (oral contraceptive, intra- uterine device, or hormonal patch, injectable, or implantable device) in conjunction with a male condom from screening until 52 weeks after dosing.

1. True abstinence from sexual intercourse, in accordance with the preferred and usual lifestyle of the subject, is acceptable. Periodic abstinence or avoiding sexual intercourse on days while the subject is fertile (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), are not acceptable methods of contraception.

2. Non-childbearing potential is defined as postmenopausal (i.e., no menses for more than 1 year prior to screening) or surgical sterility (e.g., tubal ligation, hysterectomy, and/or bilateral salpingo-oophorectomy).

7. Male subjects must either be surgically sterile (vasectomy) or agree to use a male condom during sexual intercourse from screening until 52 weeks after dosing; if the female sexual partner is of child-bearing potential, she must also use a medically acceptable form of birth control (e.g., oral contraceptive).

8. Male subjects must agree not to donate sperm from screening until 52 weeks after dosing.

9. All subjects must agree not to donate blood from screening until 52 weeks after dosing.

10. Able to read and understand the requirements of the study unaided and to provide written informed consent.

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. Use of anticoagulants or known coagulopathy.

3. Influenza, COVID-19, or other vaccination less than 14 days prior to day 1.

4. Immunosuppressive therapy, including oral (but not inhaled or topical) corticosteroids, less than 90 days prior to day 1.

5. Chronic narcotic use.

6. Injection of steroid, hyaluronate or other agent, into the target knee less than 90 days prior to day 1.

7. Receipt of an investigational product within 90 days prior to day 1.

8. Prior receipt of an AAV5 gene therapy or stem cell product.

9. Major injury to the target knee, such as torn ligament or severe sprain, within 12 months of screening.

10. Target knee effusion >2+ based on the stroke test.

11. Target knee joint space width < 1 mm on knee radiograph.

12. Valgus or varus alignment of the target knee >10 degrees on knee radiograph.

13. Dermatologic lesions on target knee within one month of screening.

14. Severe hip OA ipsilateral to the target knee.

15. Inability to complete study assessments, including self-administered questionnaires.

16. Disability so severe that the subject cannot comply with the study requirements, including knee symptoms that result in significant difficulty or inability to walk.

17. Previous cartilage repair procedures.

18. Surgery on the target knee within 180 days prior to day 1.

19. Total knee arthroplasty or other knee surgery planned in the next 12 months.

20. Donation or loss of more than 100 mL of blood within 60 days prior to day 1.

21. Pregnancy or breast-feeding, either at the time of screening or planned in the next 12 months.

22. Fracture or tumor on Magnetic Resonance Imaging (MRI) of target joint.

23. Any contraindication to MRI, e.g., pacemaker, claustrophobia, or metal in the target joint that would impact MRI quality.

24. Any of the following laboratory values: hemoglobin <8.5 gm/dL, white blood cell count <3500 per mm3 or >15,000 per mm3, platelet count <100,000 K/uL, creatinine >2 mg/dL, bilirubin >2 mg/dL, aspartate aminotransferase or alanine aminotransferase >2 times the upper limit of normal, international normalized ratio >1.2, or hemoglobin A1c >8.0%.

25. Known HIV infection, acute or chronic, uncured hepatitis C infection, or known positive serologic test for hepatitis B surface antigen.

26. 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.

1. Examples of medical conditions include but are not limited to: severe liver or kidney disease, uncompensated congestive heart failure, myocardial infarction within six months, unstable angina, uncontrolled hypertension, severe pulmonary disease or uncontrolled asthma, immunosuppressive disorders, history of cancer (other than cutaneous basal and squamous cell carcinoma) with less than five years documentation of a disease-free state, and poorly-controlled diabetes with hemoglobin A1c >8.0% at screening.

2. Examples of psychiatric conditions include but are not limited to: severe depression, suicidal ideation and drug or alcohol abuse within the past year.