Study TPX-100-5: intra-articular TPX-100 significantly delays pathological bone shape change and stabilizes cartilage in moderate to severe bilateral knee OA

Dawn McGuire, Michael Bowes, Alan Brett, Neil A Segal, Meghan Miller, David Rosen, Yoshinari Kumagai, Dawn McGuire, Michael Bowes, Alan Brett, Neil A Segal, Meghan Miller, David Rosen, Yoshinari Kumagai

Abstract

Background: TPX-100, a promotor of osteoblast and chondroblast differentiation, is a potential osteoarthritis (OA) therapy. This retrospective study compared MRI 3D femoral bone shape changes (B-scores) after intra-articular TPX-100 or placebo and analyzed the relationship between cartilage thickness and bone shape change over 12 months.

Methods: One hundred and four participants with bilateral moderate to severe knee cartilage defects were randomized to receive TPX-100 (200 mg) or placebo. Each subject's contralateral placebo-treated knee served as a paired internal control. After MRI quality control, 78/93 subjects (84%; 156 knees) were analyzed for quantitative femoral B-score and cartilage thickness. All analyses were performed centrally, blind to treatment assignment and clinical data.

Results: TPX-100-treated knees (n = 78) demonstrated a statistically significant decrease in pathologic bone shape change compared with placebo-treated knees at 6 and 12 months: 0.0298 (95% C.I. - 0.037, 0.097) vs 0.1246 (95% C.I. 0.067, 0.182) (P = 0.02), and 0.0856 (95% C.I. 0.013, 0.158) vs. 0.1969 (95% C.I. 0.123, 0.271) (P = 0.01), respectively. The correlation between bone shape change and medial and total tibiofemoral cartilage thickness changes at 12 months was statistically significant in TPX-100-treated knees (P < 0.01).

Conclusions: This is the first report of a potential therapy demonstrating a significant effect on bone shape measured by B-score in knee OA. These data, in combination with previously reported statistically significant and clinically meaningful improvements in WOMAC physical function versus placebo, support TPX-100 as a candidate for disease modification in knee OA.

Trial registration: NIH ClinicalTrials.gov, NCT01925261 . Registered 15 August 2013.

Keywords: B-score; Bone shape; DMOAD; Machine learning; Osteoarthritis; TPX-100.

Conflict of interest statement

AB and MB are employees of Imorphics, Manchester, UK. DM, MM, DR, and YK are employees of OrthoTrophix, Inc., Oakland, CA. NS reports no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT diagram for the TPX-100-1 and TPX-100-5 studies
Fig. 2
Fig. 2
Change in shape for the anterior femur (top row) and posterior femur (bottom row), for various B-scores. Red indicates where there is an increase in size (locally calculated, based on anatomically corresponded triangles from the shape model), blue indicates decrease in size (locally); scale shows percentage in area size change of each triangle. Change tends to be greatest around the edge of the cartilage plate (osteophyte region), but it also occurs in central subchondral regions where the bone flattens out. Adapted from Bowes et al. [11]
Fig. 3
Fig. 3
Femoral bone shape changes in TPX-100-treated knees and placebo-exposed knees in bilateral OA subjects and their comparison with historical bone shape change from the Osteoarthritis Initiative (OAI). All error bars represent standard errors of the mean
Fig. 4
Fig. 4
12-month femoral bone shape stabilization is associated with medial femoral condyle cartilage thickening/stabilization in the index knee. Subjects are stratified by B-score change quartiles. All error bars are standard errors of the mean

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