Allogeneic Mesenchymal Stem Cells for Osteoarthritis

A Randomized, Double Blind, Multicentric, Placebo Controlled, Phase -II Study Assessing the Safety and Efficacy of Intraarticular Ex-vivo Cultured Adult Allogeneic Mesenchymal Stem Cells in Patients With Osteoarthritis of Knee

This study is designed to know the safety and efficacy of 2 different doses of mesenchymal stem cells in patients suffering from osteoarthritis of knee joint.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of Knee Joint
• Intervention / Treatment: Biological: Ex- vivo cultured adult allogeneic MSCs; Biological: Plasmalyte-A

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• Malaysia
  • Federal territory
    • Kuala Lumpur, Federal territory, Malaysia, 56100
      • Pantai Cheras Medical Centre
  • Selangor
    • Kuala Lumpur, Selangor, Malaysia, 43300
      • Serdang Hospital
    • Kuala Lumpur, Selangor, Malaysia, 68000
      • KPJ Ampang Puteri Specialist Hospital
    • Kuala Lumpur, Selangor, Malaysia, 68100
      • Selayang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females in the age 20 - 70 years (both inclusive)
2. Radiographic evidence of grade 2 to 3 osteoarthritis based on the Kellgren and Lawrence radiographic entry criteria.
3. History of primary idiopathic osteoarthritis of the knee characterized by pain which requires intake of analgesics.
4. Self-reported difficulty in at least one of the following activities attributed to knee pain: lifting and carrying groceries, walking 400 metres, getting in and out of a chair, or going up and down stairs.
5. Patients who have been on stable medication for the past three months.
6. Patients who have not received intra articular steroids or hyaluronan within the last three months.
7. Female patients of childbearing age must be willing to use accepted methods of contraception during the course of the study
8. Ability to provide written informed consent.

Exclusion Criteria:

1. Prior or ongoing medical conditions (e.g., concomitant illness, psychiatric condition, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
2. History of surgery, including arthroscopy, or major trauma to the study joint in the previous 12 months
3. Signs of active study joint inflammation including redness, warmth, and/or, if qualifying with osteoarthritis of the knee, a large, bulging effusion of the study knee joint with the loss of normal contour of the joint at the screening visit or at the baseline examination
4. Infections in or around the knee.
5. Patients awaiting a replacement knee or hip joint
6. Patients with other conditions that cause pain
7. Significantly incapacitated or disabled and would be categorized as ACR Functional Class IV (largely or wholly incapacitated), or unable to walk without assistive devices
8. Patients with other known rheumatic or inflammatory disease such as rheumatoid arthritis
9. Other pathologic lesions on x-rays of knee
10. Positive hepatitis B surface antigen, hepatitis C antibody test, Anti human immunodeficiency virus (HIV) antibody test, or VDRL
11. History of Bleeding disorders
12. Known hypersensitivity to Hyaluronan products or animal sera
13. For women of child-bearing potential: positive pregnancy test or lactating

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: Ex- vivo cultured adult allogeneic MSCs; Single intraarticular dose of allogeneic MSCs	Biological: Ex- vivo cultured adult allogeneic MSCs; Single intraarticular dose of allogeneic MSCs suspended in 2ml Plasmalyte followed by 2ml of Hyaluronan
PLACEBO_COMPARATOR: Plasmalyte-A; Single intraarticular dose of 2ml Plasmalyte	Biological: Plasmalyte-A; Single intraarticular dose of 2ml Plasmalyte followed by 2ml Hyaluronan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and percentage of patients with adverse events as a measure of safety and tolerability	Safety evaluation will include assessment of physical examination, periodic monitoring of vital signs (heart rate, respiratory rate, blood pressure and temperature), clinical laboratory investigations (including haematology, serum chemistry, LFT, urine-analysis) and 12-lead ECG recording.; Tolerability: Adverse events monitored using information volunteered by the patients and as observed by the PI will be summarized descriptively by total number of AE(s) and compared between the study arms.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the WOMAC OA (Western Ontario and McMaster Universities Osteoarthritis) Index -pain subscale score	1 Year
Change from baseline in WOMAC OA stiffness index	1 Year
Change from baseline in WOMAC OA composite index	1 Year
Change from baseline in ICOAP (Intermittent and Constant Osteoarthritis Pain)	1 Year
Change from baseline in radiographic (X-ray) findings of knee	1 Year
Change from baseline in the WORMS score of knee using MRI	1 Year
Change from baseline in arthritis pain scores on the visual analogue scale	1 Year
Reduction in the intake of analgesic tablets from baseline	1 Year

Collaborators and Investigators

• Sponsor: Stempeutics Research Pvt Ltd
• Collaborators: Stempeutics Research Malaysia SDN BHD
• Investigators: Principal Investigator: Prof. Dr. Muhammad Ali Noor Muhd Abdul Ghani, FRCS, KPJ Ampang Puteri Specialist Hospital; Principal Investigator: Dr. Ahmad Hisham Abd. Rashid, MD., MS, Clinical Research Centre Hospital Serdang; Principal Investigator: Dr. Suntharalingam Subramaniam, FRCS, Pantai Cheras Medical Centre; Principal Investigator: Dato' Dr. Ramli Baba, MS, Selayang Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: October 5, 2011
• First Posted (ESTIMATE): October 7, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 12, 2016
• Last Update Submitted That Met QC Criteria: May 11, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Osteoarthritis; Knee; MSC; Stem cell
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: SRM/OA/10-11/001