Two years efficacy and safety outcomes of using allogeneic, pooled mesenchymal stromal cells for osteoarthritis of knee in a double-blind randomized placebo-controlled phase 3 study.

Objective: The aim of this study was to assess whether allogeneic cultured, pooled, bone marrow derived mesenchymal stromal cells (BMMSCs), has potential to impact progression of osteoarthritis (OA). Method: Randomized, double blind, multicentric, placebo-controlled trial to assess efficacy and safety of BMMSCs in Grade 2 and 3 OA of knee. 146 patients were randomized, 73 patients each received either BMMSCs (25 million cells) or placebo followed by 20 mg HA. The primary end point was evaluation of WOMAC Composite Index and secondary end points were WOMAC sub-scores, VAS, magnetic resonance (MR) assessment (T2 mapping and cartilage volume). Results: 58 patients from BMMSC arm and 60 patients from placebo arm completed 24 months follow-up. At 24 months follow up, WOMAC composite index and WOMAC sub scores showed significant improvements in cell arm as compared to placebo (p < 0.0001); T2 mapping showed there is no worsening of the cartilage in the medial femoral tibial compartment in BMMSC arm whereas placebo arm shows gradual worsening (p < 0.0001). Cartilage volume increased in BMMSC arm. At Day 90 & 730, Urinary C - terminal cross linked telopeptide of type II collagen significantly decreased in the cell arm and increased in the placebo arm (p-value<0.0001). 5 AEs were possibly related to the study drug and were local site administration effects. By 24 months follow-up, 4 patients in the placebo group underwent TKR versus 1 patient in the BMMSC arm. Conclusions: This study demonstrates that BMMSC's is safe and effective for the treatment of grade 2 & 3 OA of knee. Ctri registration: CTRI/2018/09/015785 [Registered on: September 20, 2018].