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

A Multicenter, Randomized, Placebo Controlled, Double-blind, Parallel, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Invossa K Injection in Patients Diagnosed as Knee Osteoarthritis With Kellgren & Lawrence Grade 2

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.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis
• Intervention / Treatment: Biological: Invossa K Inj.; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 146
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Ansan, Korea, Republic of
    • Korea University Anam Hospital
  • Busan, Korea, Republic of
    • Inje University Busan Paik Hospital
  • Daegu, Korea, Republic of
    • Kyungpook National University School of Medicine
  • Daejeon, Korea, Republic of
    • Chungnam National University School of Medicine
  • Hwasun, Korea, Republic of
    • Chonnam National University Hwasun Hospital
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • College of Medicine, Hanyang University
  • Seoul, Korea, Republic of
    • Ewha Womans University Mokdong Hospital
  • Seoul, Korea, Republic of
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • School of Medicine, Kyung Hee University
  • Seoul, Korea, Republic of
    • Seoul National University Borame Medical Center
  • Seoul, Korea, Republic of
    • The Catholic University of Korea College of Medicine
  • Seoul, Korea, Republic of
    • Yonsei University School of Medicine
  • Suwon, Korea, Republic of
    • Ajou University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Invossa K Inj.	Biological: Invossa K Inj.; Invossa K Inj.
Placebo Comparator: Placebo; Placebo control	Drug: Placebo; Placebo control

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC (The Western Ontario and McMaster Universities Osteoarthritis Index) score	Changes in WOMAC (score)	Week 0, 26, 39 and 52
IKDC Subjective Knee Evaluation	Changes in IKDC Subjective Knee Evaluation (score)	Week 0, 26 and 39
100 mm VAS	Changes in 100 mm VAS	Week 0, 26 and 39
OMERACT-OARSI (Outcome measures in rheumatology-Osteoarthritis research society international) response rate	OMERACT-OARSI response rate after administration (%)	Week 26, 39 and 52
MRI scan	Changes in MRI scan	Week 0, and 52
Joint Space Width	Changes in Joint Space Width (mm)	Week 0, and 52
Biomarker (CTX-I) in blood	Levels of CTX-I in blood (ng/ml)	Week 0, 26, and 52
Biomarker (CTX-II) in urine	Levels of CTX-II in urine (ng/ml)	Week 0, 26, and 52
Rescue Medication (Dosage)	Dosage of Rescue Medication (mg)	Week 0, 4, 12, 26, 39, and 52
Rescue Medication (Frequency)	Frequency of Rescue Medication (number)	Week 0, 4, 12, 26, 39, and 52
Drop-out rate	Drop-out rate (%)	Week 0, 4, 12, 26, 39, and 52
Reason of drop-out	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.).	Week 0, 4, 12, 26, 39, and 52

Collaborators and Investigators

• Sponsor: Kolon Life Science
• Investigators: Principal Investigator: Myung-Chul Lee, MD, PhD, Department of Orthopedic Surgery, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): March 30, 2020

Study Registration Dates

• First Submitted: December 11, 2017
• First Submitted That Met QC Criteria: December 19, 2017
• First Posted (Actual): December 26, 2017

Study Record Updates

• Last Update Posted (Actual): March 7, 2018
• Last Update Submitted That Met QC Criteria: March 5, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: osteoarthritis; chondrocyte cells; gene therapy
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: KS-INV-02-3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No