A clinical trial to evaluate the effects of stem cells in patients with Osteoarthritis of the Knee joint
Scientific Title of Study
A Randomized, Double blind, Multicentric, Placebo controlled, Phase III study assessing the efficacy and safety of Intra-articular administration of Stempeucel®(Adult Human Bone Marrow derived, cultured, pooled, allogenic Mesenchymal stromal cells)in patients with Osteoarthritis of Knee
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
SRPL/OA/16-17/001; Version No 3.0 dated 05 Jul 2018
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Pawan Gupta
Designation
Vice President- Medical Affairs
Affiliation
Stempeutics Research Pvt Ltd
Address
Stempeutics Research Pvt Ltd
3rd Floor, Manipal Hospitals Whitefield Pvt Ltd.
# 143, 212-215, EPIP Industrial Area, ITPL Main Road,
Bangalore KARNATAKA 560048 India
Phone
91-80-25028101
Fax
Email
pawan.gupta@stempeutics.com
Details of Contact Person Scientific Query
Name
Dr Pawan Gupta
Designation
Vice President- Medical Affairs
Affiliation
Stempeutics Research Pvt Ltd
Address
Stempeutics Research Pvt Ltd
3rd Floor, Manipal Hospitals Whitefield Pvt Ltd.
# 143, 212-215, EPIP Industrial Area, ITPL Main Road,
Bangalore KARNATAKA 560048 India
Phone
91-80-25028101
Fax
Email
pawan.gupta@stempeutics.com
Details of Contact Person Public Query
Name
Jijy Abraham
Designation
Senior Executive-Regulatory & Clinical Trials
Affiliation
Stempeutics Research Pvt Ltd
Address
Stempeutics Research Pvt Ltd
3rd Floor, Manipal Hospitals Whitefield Pvt Ltd.
# 143, 212-215, EPIP Industrial Area, ITPL Main Road,
Bangalore KARNATAKA 560048 India
Phone
91-80-25028112
Fax
Email
jijy.abraham@stempeutics.com
Source of Monetary or Material Support
Stempeutics Research Pvt Ltd
3rd floor Manipal Hospitals Whitefield,
#143, 212-215, EPIP Industrial Area, ITPL Main Road, Bangalore - 560048
Medilink Hospital Research Centre, Basement Medilink Hospital, Nr. Shyamal Cross Road, 132 ft Ring road, Satellite, Ahmedabad, 380015, Ahmadabad GUJARAT
9898983555
maheshwarisunil@live.com
Dr Vijay Goni
Postgraduate Institute of Medical Education and Research,Chandigarh
"C- Block, Room no 003, Department of Immunology Sanjay Gandhi Post Graduate Institute of Medical Sciences Raebareli Road, Lucknow - 226 014
"
Chandigarh CHANDIGARH
91-7087009747
vijaygoni@gmail.com
Dr Parag Kantilal Sancheti
Sancheti Institute for Orthopaedics & Rehabilitation
Room No. 03, Department of Orthopaedics, Sancheti Institute for Orthopaedics & Rehabilitation, Clinical Research Division, 1st Floor, Sancheti Research Department, 16 Shivaji Nagar, Pune 411005, Maharashtra, India
Pune MAHARASHTRA
Sanjay Gandhi Post Graduate Institute of Medical Sciences
"C- Block, Room no 003, Department of Immunology Sanjay Gandhi Post Graduate Institute of Medical Sciences Raebareli Road, Lucknow - 226 014
Lucknow UTTAR PRADESH
91-522-2494318 91-522-2668812 vikasagr@yahoo.com
Dr Purohit Sharad Prahaladbhai
Sanjivani Super specialty Hospital Pvt Ltd.Ahmadabad
Uday park society, Nr. Sunrise park, Vastrapur, Ahmedabad- 380015 Ahmadabad GUJARAT
Ethical Review Board, M. S. Ramaiah Memorial Hospital
Approved
Ethics committee of SMS Medical College and Attached Hospitals Office of Ethics Committee First Floor, Allergy Clinic, Dhanwantri, OPD Block SMS Hospital, JLN Marg, Jaipur – 302004
Approved
Ethics Committee,Medilink Hospital
Approved
Institutional Ethics Committee, Apollo Gleneagles Hospitals, 58-Canal circular road, Kolkata, 700054, West Bengal
Approved
Institutional Ethics Committee, PGIMER Room no. 6006, IEC office, A, 6th floor, PN Chuttani Block, PGIMER Chandigarh 160012, India
Approved
Institutional Ethics Committee, St.Johns Medical college & Hospital
Approved
Institutional Ethics Committee“, All India Institute of Medical Sciences Bhubaneswar, AIIMS Road, Sijua, Patrapada, Bhubaneswar, Odisha 751019, India
Approved
Institutional Ethics Committee“, King George Hospital, Maharanipeta, Visakhapatnam- 530002, Andhra Pradesh, India
Approved
LPR ethics Ethics Committee, Lifepoint Multispecialtiy Hospital Pvt ltd situated at 145/1 Mumbai Banglore Higway Near Hotel Sayaji Wakad Pune 411057 Maharashtra India
Approved
MAHE Ethics Committee
Approved
Manipal University Ethics Committee
Approved
Sancheti Institutional Review Board
Approved
Sanjivani Hospital Ethics Committee
Approved
SGPGI Ethics Committee, Lucknow
Approved
Yashoda Academy of Medical Education and Research (YAMER-IEC)“, Yashoda hospital, Behind Hari Hara Kala bhawan, Secunderabad - 500003, Telangana, India
Single intraarticular dose of 1 ml CryoStor
CS5® + 1 ml PlasmaLyte A followed by 2
ml hyaluronan. It is a one time injection at baseline.
Intervention
Stempeucel®
Single intra-articular dose of 25 million
human bone marrow derived mesenchymal
stromal cells, stempeucel® suspended in 1
ml CryoStor CS5® + 1 ml PlasmaLyte A
followed by 2 ml hyaluronan. It is a one time injection at baseline.
Inclusion Criteria
Age From
40.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Males or females in the age 40 – 65 years (both inclusive)
2. History of primary osteoarthritis of the knee characterized by pain which requires intake of analgesics
3. Self-reported difficulty in at least one of the following activities attributed to knee pain: lifting and carrying groceries, walking 400 meters, getting in and out of a chair, getting up from squatting or cross leg position or going up and down stairs
4. Patient on analgesic medication for OA, for 6 weeks based on Investigator’s feedback.
5. Radiological criteria
X-ray knee joint showing radiographic evidence of grade 2 to 3 osteoarthritis based on the Kellgren and Lawrence radiographic criteria (based on site radiologist report).
6. Willing to refrain from any other stem cell treatment for 2 year during the study.
7. Female patients of childbearing age must be willing to use accepted methods of contraception during the course of the study
8. Willing to provide written informed consent including audio-video consent
ExclusionCriteria
Details
1. X-ray (evaluated by central radiologist) showing any of the following:
a. Grade 0, 1 and 4 osteoarthritis based on the Kellgren and Lawrence radiographic criteria
b. Subchondral sclerosis
2. MRI knee (evaluated by central radiologist) showing any of the following:
a. ACL/ PCL tears
b. Meniscal tears: Grade 3 tears - defined as increased signal intensity on PD sequences extending up to either articular surface. It also includes root tear but excludes RAMP tear
c. Patients with exclusive patello-femoral arthritis
d. Grade 0, 1 and 4 arthritis as per the proposed grading on MRI
3. Prior or ongoing medical conditions (e.g., concomitant illness, psychiatric condition), alcoholism, smoking, tobacco chewing or 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
4. History of surgery or major trauma to the study joint
5. Arthroscopy on the study joint in the previous 12 months
6. 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
7. Acute exacerbations of the study joint in the past 6 weeks
8. Patients who had received intra-articular steroids or hyaluronan within the last 3 months
9. Patients who had taken any stem cell treatment in the past by any route of administration
10. Infections in or around the study knee
11. Patients awaiting a replacement of knee or hip joint
12. Patients with other conditions that cause pain in the knee joint
13. Patients with gross deformity (varus by x-ray of the knee or flexion deformity > 10° by gonometer) of the knee joint based on PI judgment
14. Significantly incapacitated or disabled and would be categorized as ACR Functional Class IV (largely or wholly incapacitated), or unable to walk without assistive devices
15. Patients with any secondary causes of arthritis e.g. rheumatoid arthritis, systemic lupus erythematous, ulcerative colitis, psoriasis, rheumatic or inflammatory disease
16. Patients with BMI ≥30 kg/m2
17. Positive hepatitis B surface antigen, hepatitis C antibody test, Anti human immunodeficiency virus – I & II (HIV – I & II) antibody test, TPHA or CMV (IgM)
18. History of Bleeding disorders
19. Known hypersensitivity to hyaluronan products or animal sera or constituents of IMP
20. Pregnancy, breast-feeding, planned pregnancy during the study, or women of child-bearing potential not using adequate contraception
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
To assess the change from baseline to one year in WOMAC (Western Ontario and McMaster Universities Osteoarthritis) Osteoarthritis Composite Index score as compared to the placebo arm
1 year
Secondary Outcome
Outcome
TimePoints
To assess the change from baseline to two year in WOMAC
To assess the change from baseline to one year and two years follow-up as compared to the placebo arm in
1. WOMAC OA Pain Index
2. WOMAC OA Stiffness Index
3. WOMAC OA Physical Function Index
Patients Assessment of Osteoarthritis Pain by VAS
Assess the quality of articular cartilage by T2 mapping
Cartilage thickness-MRI
Cartilage volume-MRI
Reduction in intake of analgesics
2 years
Target Sample Size
Total Sample Size="146" Sample Size from India="146" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This study is randomized, double blind, multi-centric, placebo controlled, single dose phase 3 study to evaluate the efficacy and safety of bone marrow derived allogeneic mesenchymal stromal cells in patients with osteoarthritis of knee joint