INTERIM REVIEW OF EFFICACY FROM A FIRST-IN-HUMAN PHASE 1/2A CLINICAL STUDY OF ICM-203, AN INTRA-ARTICULAR, AAV GENE THERAPY FOR OSTEOARTHRITIS

Abstract

INTRODUCTION

ICM-203, a recombinant AAV vector designed to express a truncated form of human Nkx3.2, a transcription factor which plays an important role in both chondrocyte and synoviocyte activity, is in clinical development as a potential DMOAD.

OBJECTIVE

An objective of this first-in-human phase 1/2a study is to assess the biological activity of ICM-203 by correlating changes in structural MRI findings with changes in measures of pain and function.

METHODS

In this double-blind, placebo-controlled, dose escalation study, subjects with KLG 2 or KLG 3 knee OA and minimum JSW > 1mm receive a single intra-articular (IA) injection of ICM-203 or placebo in a 3:1 ratio, with planned dose escalation of ICM-203 from 6 × 10¹² vector genomes (vg) to 2 × 10¹³ vg and then 6 × 10¹³ vg. The primary efficacy endpoints are changes in knee pain as assessed on a numerical rating scale (NRS); changes in knee function as measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS) activities of daily living (ADL) subscore, as well as structural knee changes, including changes in MRI OA Knee Score (MOAKS). Here, blinded efficacy data from 8 subjects in the low-dose cohort treated with ICM-203 (n=6) or placebo (n=2) are reported.

RESULTS

The low-dose cohort consisted of females aged 56 to 73 years, all with KLG 3 knee OA. Knee pain (NRS) decreased in 6 of 8 subjects and knee function (KOOS ADL) improved in 4 of 8 subjects between Day 1 and Week 52. Cartilage thickness was preserved or improved in 5 of 8 subjects and BM lesions improved in 3 of 8 subjects at Week 52. Osteophytes were unchanged in 7 of 8 subjects and only worsened minimally in 1 of 8 subjects at Week 52. Synovitis (Hoffa + effusion) improved at Week 52 in 2 of 2 subjects with more severe inflammation (synovitis score >4) at baseline. Evaluation of changes between baseline and Week 24 and baseline and Week 52 show that a decrease in the number of subregions with BM lesions was correlated with decrease in knee pain (NRS) and improvement in knee function (KOOS ADL).

CONCLUSION

IA injections of ICM-203 6 × 10¹² vg may demonstrate potential as a DMOAD, between delaying structural joint damage, alleviating synovial inflammation, and ameliorating OA symptoms. Decrease in the number of subregions with BM lesions correlated with decrease in pain and improvement in function. Investigation of higher doses is underway.