Summary

The results of this phase 1/2a study suggest that intramuscular IMMUNA injection treatment for knee osteoarthritis has a low rate of adverse reaction and led to early improvements in walking speed and knee pain and function, warranting further studies of efficacy in a larger group of patients.

Abstract

Introduction

Quadriceps muscle weakness has been shown to correlate with symptoms of pain and dysfunction attributed to knee osteoarthritis (OA). IMMUNA is a secretome product derived from partially differentiated human embryonic stem cells and is composed of a multitude of pro-myogenic factors involved in immunomodulation, cytoskeleton remodeling, and growth factor-mediated cellular signaling. IND-enabling efficacy studies have demonstrated that intramuscular IMMUNA injection treatment increases muscle mass and strength while diminishing muscle fibrosis. The purpose of this first-in-human study was to assess the safety, tolerability, and early efficacy of intramuscular IMMUNA injection for the treatment of knee OA.

Methods

A total of 9 patients were enrolled in this nonrandomized, dose-escalation phase 1/2a study, with n=3 patients per the 3 doses tested (225 ug, 450 ug, and 900 ug corresponding to 50%, 100%, and 200% human equivalent dose). Inclusion criteria included age between 50 to 75 years, mild-to-moderate knee OA as defined by Kellgren-Lawrence grade 2/3, quadriceps weakness (<7.5 N/kg/m2), and failure of one or more nonoperative treatments within the past 2 years. Patents were excluded if they had prior arthroplasty in the affected knee, uncontrolled medical co-morbidities, or received an intra-articular injection within 3 months prior to the first IMMUNA dose. In each patient, a total of 8 intramuscular IMMUNA injections were administered to the distal quadriceps muscle, alternating between the rectus femoris and vastus lateralis, over a 4-week period (2 injections/week). The trial was started with 3 patients receiving the lowest dose treatment (225 ug), and if there was no dose-limiting toxicity at the tested dose, the next higher dose cohort was enrolled. Outcomes were measured at baseline and up to 3 months post-treatment. Quadricep muscle volume was measured on MRI. Physical function and pain were assessed on a 6-minute walk test and patient-reported outcome measures (PROMIS-physical function [PF], PROMIS-pain, VAS, and WOMAC).

Results

Among the 9 patients, the mean age 67.7 years old, and the ratio of females:males was 7:2. There were no severe adverse events for any of the doses tested and only two grade 1 adverse events for local injection-site pain, which fully resolved within 48 hours after injection. At the completion of the 4-week treatment period, mean quadricep muscle volumes increased by 1.9% in the treated leg and 3.0% in the contralateral untreated leg. All patients except one showed clinically meaningful improvements in walking distance and speed on the 6-minute walk test. Patients reported clinically significant improvements in PROMIS-PF, PROMIS-pain, VAS, and WOMAC scores up to 3 months post-treatment. No appreciable differences in patient outcomes were observed among the 3 doses tested.

Discussion And Conclusion

The results of this phase 1/2a study suggest that intramuscular IMMUNA injection treatment has a low rate of adverse reaction, warranting further studies of efficacy in a larger group of patients. This initial cohort also showed early improvements in walking speed and knee pain and function. This novel treatment represents a new paradigm for treating mild-to-moderate knee OA and may have applications for accelerating rehabilitation and reversing quadriceps atrophy after knee surgery.