Assessment of Protective Effect of JOINS on Cartilage in Knee Osteoarthritis (Joins_Carp_Ⅳ)

A Randomized, Double Blinded, Parallel Group, Placebo-controlled Clinical Trial to Assess the Protective Effect of JOINS on Cartilage in Knee Osteoarthritis

• A Pilot study
• Randomized and Double-blinded
• Placebo controlled
• In 2 parallel group (JOINS 200mg:Placebo = 1:1)
• Overall 24 months treatment (JOINS:Placebo comparison up to 12 months, Additional follow-up assessment up to 24 months)
• Provide rescue medicine throughout whole clinical trial period.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: JOINS 200mg; Drug: Placebo

Detailed Description

1. Assessment of Efficacy

   1. Knee MRI(Magnetic resonance imaging):

      • Assessment of cartilage volume, thickness in target knee
      • GAG(glycosaminoglycan) concentration of target knee
      • Assessment of Whole-Organ Magnetic Resonance Imaging Score (WORMS) of target knee

   2. Knee radiography:

      • Assessment of changes in minimal medial JSW(Joint Space Width) of target knee.

   3. Knee pain(VAS)

      • Assessment changes of pain in target knee.

   4. K-WOMAC(Western Ontario and McMaster Universities Osteoarthritis Index for Korean)

      • Assessment score change for pain(5 questions), stiffness(2 questions) and physical function(17 questions).
      • The questionnaire is self-administered by the patients.
   5. Used frequency of rescue medicine.

   6. Biochemical cartilage and bone markers

      • Blood and urine sample will be collected all through the morning after a night fasting period since 10 pm the previous day to avoid the variations.

2. Assessment of Safety

   1. Adverse event
   2. Laboratory assessment
   3. Vital sign
   4. 12-lead ECG
   5. Physical examination
3. Enrollment: 76

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A female is eligible if she is of:

   • Non-child bearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is at least 2 year after post- menopausal
   • Child bearing potential and agrees to the acceptable contraceptive methods used consistently and correctly
   • Pregnancy test result of negative at screening

2. Primary Knee OA(Osteoarthritis) on medial femorotibial compartment based on ACR(American College Rheumatology) Criteria.

   • ACR Criteria : With Knee pain and satisfied at least 1 of 3 (① age > 50 years, morning stiffness < 30 minute, ③ Presence of Crepitus and Osteophytes on motion)
3. Appropriately signed and dated informed consent has been obtained

Exclusion Criteria:

1. Rheumatoid arthritis or inflammatory arthritis.
2. Bilateral total knee replacement already treated, or planning for the procedure.
3. Knee prosthesis already implanted, or foreseen within the next year.
4. Clinically significant hip osteoarthritis.
5. Severe renal insufficiency defined as creatinine clearance < 30ml/mln(Cockcroft formula).
6. Clinically significant pulmonary, hepatic, renal or heart disorder or diagnosis crucial disease by investigator ( Glycosuria(Diabetes mellitus) or asthma patients are excluded from this clinical study and the patients who has a clinically significant disease are also excluded.).
7. MRI contraindications : overweight, inferior limb diameter non-fitting the knee antenna, inserted pace-maker, metallic prosthesis( if known to interfere with MRI procedure or if known to be unsafe for MRI), metallic clips, insulin pump, cytostatic pump, hearing aid, essential tremor, claustrophobia, etc,.
8. Allergic reaction to Clinical trial medication.
9. Other clinical trial drugs during the 1 month prior to the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: JOINS 200mg; One tablet of JOINS 200mg is administered three times a day for 1 year. The subjects who consent to participate in an extension study are treated with JOINS 200mg for another 1 year.	Drug: JOINS 200mg; 1 tablet at each time, 3 times a day; Other Names: JOINS
PLACEBO_COMPARATOR: Placebo; One tablet of Placebo is administered three times a day for 1 year. The subjects who consent to participate in an extension study are treated with Placebo for another 1 year.	Drug: Placebo; placebo of Joins 200mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Knee MRI	up to 4 times

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee radiography		up to 4 times
Knee pain(VAS)		up to 6 times
K-WOMAC		up to 6 times
Consumption of rescue medication	The quantity of rescue medicine will be counted by investigator and recorded in official clinical research document form.	up to 6 times
Biomarker	Patients will need to be strictly fasting from the night before the visit. The data of biological cartilage and bone markers will be collected.	up to 6 times

Collaborators and Investigators

• Sponsor: SK Chemicals Co., Ltd.
• Investigators: Principal Investigator: Myoungchul Lee, PH.D.., Orthopedics, Seoul National University hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: November 23, 2010
• First Submitted That Met QC Criteria: February 9, 2011
• First Posted (ESTIMATE): February 11, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): April 24, 2015
• Last Update Submitted That Met QC Criteria: April 23, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: knee osteoarthritis; cartilage; protective effect
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: Joins_Carp_IV_2009