A Phase 2b/3a Study to Evaluate the Efficacy and Safety of JointStem in Patients Diagnosed as Knee Osteoarthritis

Osteoarthritis, Knee Clinical Trial

Official title:

A 48-Weeks, Phase 2b/3a, Double-Blind, Randomized, Placebo Controlled, Multi-center, Superiority Study to Evaluate the Efficacy and Safety of JointStem, Autologous Adipose Tissue Derived Mesenchymal Stem Cells in Patients Diagnosed as Knee Osteoarthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04368806
• Other study ID #: JS-OAP3-US01
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 26, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2023
• Source: Nature Cell Co. Ltd.
• Contact: Hugh Lee
• Phone: 301-540-2600
• Email: hughlee[@]kcrnresearch.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a double-blind, randomized, placebo controlled, multi-center, superiority study to evaluate the efficacy and safety of JointStem, autologous adipose tissue derived mesenchymal stem cells (AdMSC), in patients diagnosed as knee osteoarthritis. Following a 2-week screening period, approximately 140 subjects will be randomly assigned into one of the following two arms in a 1:1 ratio (1 JointStem : 1 Placebo). After each subject completes 48-Weeks visit (Visit 8) and the data management team confirms all individual data have no issue, the individual database will be locked and the blinding will be open for the statistical analysis.

Description:

Study Procedures:

• Visit 1 (Week -7) - Screening

• Visit 2 (Week -5) - Baseline and Randomization (Lipoaspiration)

• Visit 3 (Week 0) - Treatment (Intra-articular injection)

• Visit 4 (Week 4) - 4 weeks follow-up

• Visit 5 (Week 12) - 12 weeks follow-up

• Visit 6 (Week 24) - 24 weeks follow-up

• Visit 7 (Week 36) - 36 weeks follow-up

• Visit 8 (Week 48) - 48 weeks follow-up (End of Study)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject who had osteoarthritis of knee diagnosed (according to the clinical and American College of Rheumatology Criteria)

• Subject who has = 34 on WOMAC function score at Screening and Baseline

• Subject who has knee pain = 70 mm for one knee out of 100 mm on VAS (Visual Analog Scale) at Screening and Baseline

• Subject who has radiographic evidence of grade 3 osteoarthritis in the study knee based on the Kellgren and Lawrence radiographic criteria.

• Subjects whose knee pain persists for at least 12 weeks (about 3 months) prior to screening and does not improve symptoms with non-operative treatment options

• Subject who is willing to discontinue all pain medications for osteoarthritis except rescue medication (< acetaminophen 3.25 g per day) at least 72 hours prior to screening and throughout the duration of study

• Subject who is willing and able to give written informed consent for participation in the study

Exclusion Criteria:

• Subject who has Body Mass Index (BMI) > 35 kg/m2

• Subject judged by the investigator to have a history of clinically significant disease

• Subject who has any of following clinically significant disease

• Autoimmune diseases

• Paget's disease, ochronosis, acromegaly, hemochromatosis, or Wilson's disease

• Genetic diseases (hyperkinesia, collagen gene abnormality, etc.)

• Inflammatory joint disorders (e.g. rheumatoid inflammation)

• Infectious joint disorders (e.g. septic arthritis)

• Other joint disorders (e.g. gout, recurrent pseudogout, articular fracture, primary osteochondrosis, villonodular synovitis)

• Subject who has any history of cancer or currently receiving treatment for a current cancer diagnosis

• Subject who is positive in pathogenic test (HIV, viral hepatitis, or syphilis)

• Subject who has heart diseases (myocardial infarction, coronary artery bypass graft surgery, arrhythmia, or other serious heart diseases) or has history of heart diseases within 6 months prior to Screening

• Subject who have received any intra-articular therapy in any joint within 6 months prior to Screening, or surgery on the relevant knee including articular endoscopic procedures within 6 months prior to Screening

• Subject who has history of prolotherapy, or platelet rich plasma injection within 6 months prior to Screening

• Subject who have received long-acting hyaluronic acid injection (e.g. Synvisc-One®, etc.) within 6 months prior to Screening

• Subject who has history of stem cell therapy

• Subject who have significant lab abnormalities for the following parameters (If the value is within 10% of the listed laboratory exclusion criterion value and the value is considered not to be clinically significant by the investigator, the subject can be considered for enrollment):

• Serum ALT and AST > 2 x upper limit of normal

• Serum creatinine out of normal range

• PT/INR out of normal range

• Hemoglobin < 10 g/dL for female subject and hemoglobin < 11 g/dL for male subject

• Platelets out of normal range

• Subject for whom the investigator judges the lipoaspiration can cause any problem

• Subject who has history of local anesthetic allergy

• Subject who has taken anti-inflammatory drugs (prescription and non-prescription NSAIDs), symptomatic slow acting drugs (glucosamine, chondroitin sulfate, diacerhein etc.), or oral steroids (prednisone etc.) within 14 days prior to Screening (however, those who undergo a 14-day wash-out period can participate.)

• Subject who is an active drug/alcohol abuser

• Pregnant or breast-feeding women, or women or men who are not using appropriate method of contraception (appropriate method includes hormones, bilateral tubal ligation, and barrier method with spermicide, and intra-uterine device for women and vasectomy and barrier method with spermicide for men; subjects should agree to use appropriate method)

• Subject who is enrolled in any other clinical trials within 3 months from Screening

• Subject who received the COVID-19 vaccines within 1 week from Visit 2 (Lipoaspiration, baseline)

• Subject who the principal investigator considers inappropriate for the study due to any other reasons than those listed above

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• JointStem
Autologous Adipose tissue derived Mesenchymal Stem Cells (AdMSC)

Other:
• Placebo Control
Normal Saline with autologous Serum

Locations

Country	Name	City	State
United States	TriWest Research Associates	El Cajon	California
United States	BioSolutions Clinical Research Center	La Mesa	California
United States	Neurovations Research	Napa	California
United States	Newport Therapeutics	Newport Beach	California
United States	Source Healthcare	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Nature Cell Co. Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Western Ontario and McMaster Universities Arthritis Index (WOMAC) function Score	Change from baseline in WOMAC function score at Week 48	Baseline and Week 48
Primary	Visual Analog Scale (VAS) score	Change from baseline on Visual Analog Scale (VAS) score at Week 48	Baseline and Week 48
Secondary	Western Ontario and McMaster Universities Arthritis Index (WOMAC) subscale (Function)	Change from baseline in WOMAC subscale (Function) score at Week 12, 24, and 36	Week 12, 24 and 36
Secondary	Western Ontario and McMaster Universities Arthritis Index (WOMAC) subscale (Pain)	Change from baseline in WOMAC subscale (Pain) score at Week 12, 24, 36, and 48	Week 12, 24, 36, and 48
Secondary	Total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score	Change from baseline in total WOMAC score at Week 12, 24, 36, and 48	Week 12, 24, 36, and 48
Secondary	Visual Analog Scale (VAS) score	Change from baseline in VAS score at Week 12, 24 and 36	Week 12, 24 and 36
Secondary	International Knee Documentation Committee (IKDC) score	Change from baseline in IKDC score at Week 12, 24, 36, and 48	Week 12, 24, 36, and 48
Secondary	36-Item Short Form health survey questionnaires (SF-36) score	Change from baseline in SF-36 score at Week 12, 24, 36, and 48	Week12, 24, 36, and 48
Secondary	Kellgren-Lawrence grade	Change from baseline in Kellgren-Lawrence grade of knee osteoarthritis determined by X-ray at Week 48	Week 48
Secondary	Number and amount of rescue medication use	The number and amount of rescue medication use at Week 12, 24, 36, and 48	Week 12, 24, 36, and 48