The Efficacy and Safety of Invossa K Injection in Patients Diagnosed With Knee Osteoarthritis

Phase 3

• Conditions: Osteoarthritis
• Interventions: Drug: Placebo; Biological: Invossa K Inj.

• Registration Number: NCT03383471
• Lead Sponsor: Kolon Life Science

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of intraarticular Invossa K Injection patients diagnosed with Kellgren \& Lawrence grade 2 knee osteoarthritis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-12-11
• Study First Submitted QC: 2017-12-19
• Study First Posted: 2017-12-26
• Study Start: 2018-02-12
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-05
• Last Update Posted: 2018-03-07
• Primary Completion: 2019-12-31
• Study Completion: 2020-03-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 146

Inclusion Criteria

1. Male or female aged 19 and older

2. Patients with IKDC Subjective Knee Evaluation of ≤ 60 of the target knee.

3. Patients with a score of ≥ 40 on the 100 mm pain VAS of the target knee.

4. Patients with grade 2 osteoarthritis as determined by the radiographic criteria of Kellgren and Lawrence

5. BMI should fall between 18.5 and 30

6. Patients who satisfies the clinical/radiational criteria by the American College of Rheumatology guidelines, and applies to one of the following.

   • Age > 50 years old
   • Morning stiffness < 30 minutes
   • Crepitus and Osteophytes

7. With major lesions concentrated in one section of the knee, and with the major lesions considered the main cause of the clinical symptoms

8. Patients with persistent symptoms in spite of conservative therapy for more than 3 months : Improvement of 100 mm VAS are less than 10 mm after 3 months

9. Healthy, with no major findings from the physical examination, hematology, serum chemistry, and urine tests, and no significant medical history

10. Agreed to use an effective contraceptive method during the study period

11. Voluntarily agreed to participate in this study, and signed the informed consent form

Exclusion Criteria

1. Patients who had been administered with drugs such as oriental medicine, glucosamine and chondroitin within 14 days of baseline visit (But, possible to include after 14 days of wash-out period)

2. Patients taking steroidal anti-inflammatory medications within 14 days of baseline visit (But, possible to include after 14 days of wash-out period)

3. Patients with severe pain in other areas that could effect the diagnosis of the symptoms

4. Patients over Grade 3 osteoarthritis as determined by the radiographic criteria of Kellgren and Lawrence

5. History of surgery like arthroendoscopy within the past 6 months on the target knee

6. Patients who had been administered with immunosuppressants, including antirheumatic drugs (including methotrexate or antimetabolite), within the past 3 months

7. History of injection within the past 3 months on the target knee

8. Pregnant or breastfeeding female

9. With another joint disease apart from degenerative arthritis

10. Patients with hepatitis including carrier

11. Patients with HIV and an infectious disease which is clinically uncontrolled

12. Patients who have any of the following clinically significant diseases or have a medical history within 6 months :

    • Clinically significant heart diseases which are considered by the investigator
    • Uncontrolled hypertension : if the systolic blood pressure exceeds 160 mmHg or diastolic blood pressure exceeds 100 mmHg in a sitting position
    • Kidney disease
    • Liver disease
    • Endocrine disease
    • Uncontrolled diabetes mellitus : HbA1c ≥ 9%
    • Paget's disease, ochronosis, acromegaly, hemochromatosis, Wilson's disease
    • Genetic diseases (hyperkinesia, collagen gene abnormality)

13. Medical history of past or current malignant tumor

14. Patients with a history of anaphylactic reactions

15. Patients with a history of hypersensitivity reactions to the components of this drug, including dimethylsulfoxide, mannitol, dextran 40 or bovine proteins

16. Participated in another clinical trial (using the investigational drug or a medical device) within 30 days before enrollment in this study

17. Patients who administered the INVOSSA K inj.

18. Considered inappropriate by the investigator for participation in this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo control
Invossa K Inj.	Invossa K Inj.	Invossa K Inj.

Primary Outcome Measures

Name	Time	Method
IKDC (International knee documentation committee) Subjective Knee Evaluation	Week 0 and 52	Changes in IKDC Subjective Knee Evaluation (score)
100 mm VAS (Visual analogue scale)	Week 0 and 52	Changes in 100 mm VAS

Secondary Outcome Measures

Name	Time	Method
IKDC Subjective Knee Evaluation	Week 0, 26 and 39	Changes in IKDC Subjective Knee Evaluation (score)
Biomarker (CTX-I) in blood	Week 0, 26, and 52	Levels of CTX-I in blood (ng/ml)
Rescue Medication (Frequency)	Week 0, 4, 12, 26, 39, and 52	Frequency of Rescue Medication (number)
MRI scan	Week 0, and 52	Changes in MRI scan
Rescue Medication (Dosage)	Week 0, 4, 12, 26, 39, and 52	Dosage of Rescue Medication (mg)
Drop-out rate	Week 0, 4, 12, 26, 39, and 52	Drop-out rate (%)
Reason of drop-out	Week 0, 4, 12, 26, 39, and 52	Reason of drop-out is recorded in CRF (Case Report Form), when the patient is dropped-out according to drop-out criteria (e.g. Withdraw a consent, Patients who can not continuously participate in study due to adverse events, Impossible to follow-up of the patient. etc.).
100 mm VAS	Week 0, 26 and 39	Changes in 100 mm VAS
Joint Space Width	Week 0, and 52	Changes in Joint Space Width (mm)
WOMAC (The Western Ontario and McMaster Universities Osteoarthritis Index) score	Week 0, 26, 39 and 52	Changes in WOMAC (score)
OMERACT-OARSI (Outcome measures in rheumatology-Osteoarthritis research society international) response rate	Week 26, 39 and 52	OMERACT-OARSI response rate after administration (%)
Biomarker (CTX-II) in urine	Week 0, 26, and 52	Levels of CTX-II in urine (ng/ml)

Trial Locations

Locations (17)

Inje University Busan Paik Hospital; 🇰🇷 Busan, Korea, Republic of

Seoul National University Borame Medical Center; 🇰🇷 Seoul, Korea, Republic of

Ewha Womans University Mokdong Hospital; 🇰🇷 Seoul, Korea, Republic of

Inha University Hospital; 🇰🇷 Incheon, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Yonsei University School of Medicine; 🇰🇷 Seoul, Korea, Republic of

Ajou University School of Medicine; 🇰🇷 Suwon, Korea, Republic of

Kyungpook National University School of Medicine; 🇰🇷 Daegu, Korea, Republic of

Chungnam National University School of Medicine; 🇰🇷 Daejeon, Korea, Republic of

School of Medicine, Kyung Hee University; 🇰🇷 Seoul, Korea, Republic of

Chonnam National University Hwasun Hospital; 🇰🇷 Hwasun, Korea, Republic of

The Catholic University of Korea College of Medicine; 🇰🇷 Seoul, Korea, Republic of

College of Medicine, Hanyang University; 🇰🇷 Seoul, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Ansan, Korea, Republic of

Konkuk University Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of