Xalud Therapeutics, a clinical-stage biotechnology company developing novel non-viral gene therapies to treat pathologic inflammation, today announced pooled gait data from a world-renowned gait laboratory in Adelaide, Australia, which served as a study site for two studies of lead candidate XT-150 in patients with knee osteoarthritis (OA).
• Results demonstrate that XT-150 can facilitate improved knee function during walking gait, which persists to 180 days following a single injection
NEW YORK, March 20, 2023 (GLOBE NEWSWIRE) -- Xalud Therapeutics, a clinical-stage biotechnology company developing novel non-viral gene therapies to treat pathologic inflammation, today announced pooled gait data from a world-renowned gait laboratory in Adelaide, Australia, which served as a study site for two studies of lead candidate XT-150 in patients with knee osteoarthritis (OA). XT-150 is a locally injectable plasmid DNA (pDNA)-delivered gene therapy expressing IL-10v, a proprietary modified version of interleukin-10 (IL-10), which Xalud is evaluating across a broad range of chronic inflammatory diseases in clinical and preclinical studies.
The results demonstrate a positive signal supporting the use of XT-150 as a potential effective treatment in knee OA with the goal of improving joint function. The data were presented in a poster presentation titled “Functional improvements in knee kinematics during walking gait over six months following treatment with XT-150: pooled results from two clinical trials” at the 2023 Osteoarthritis Research Society International (OARSI) World Congress.
“We’re pleased to share these encouraging gait data at this year’s OARSI Congress as they demonstrate support for how this novel gene therapy can improve knee function including knee range of motion (ROM) and walking speed,” said Dominic Thewlis, Ph.D., principal investigator of the study and associate professor at Adelaide Medical School. “Of note, some of the patients were able to exceed the walking speed required to cross a road safely, which is an example of how XT-150 may impact everyday activities.”
Howard Rutman, M.D., MBA, chief medical officer at Xalud Therapeutics, added, “The proposed mechanism of activity of XT-150 is to induce the local production and release of IL-10v. We believe that this supplements the body’s own IL-10 activity and may restore immune system homeostasis in chronic inflammatory diseases such as knee OA. The improvements in knee function in this gait analysis are a critical part of supporting our hypothesis of how XT-150 may be impacting the molecular changes at play in chronic inflammation.”
Study Design
The aim of this gait analysis was to investigate the effect of two different doses of intraarticular (IA) XT-150 versus a placebo control on knee biomechanics during walking gait over the course of 180 days in people with moderate to severe knee OA. Xalud has included gait analysis as part of its multi-study development program to provide functional assessment in addition to patient reported outcomes. The Phase 1 trial (NCT03282149) was conducted at a single center, and the Phase 2b trial (NCT04124042) was a multi-center (n=6) trial. Both trials used a standardized gait analysis assessment conducted at a single site in Adelaide, Australia. Participants with knee OA were randomized to one of three groups: 1) inactive placebo (saline), (2) low active dose (150 µg of XT-150) or (3) high active dose (450 µg of XT-150). Quantitative gait analysis was performed prior to intervention and at 30-, 60-, 120- and 180-days post intervention. Sixty-two people were recruited with sixty receiving an intervention.
Summary of Data
The primary outcome measure used in these analyses was an objective measure of function from a three-dimensional (3D) gait analysis of walking at a self-selected speed.
Knee joint ROM over a complete gait cycle
- From baseline to day 180, the knee ROM increased by 4° for the 150 µg group and by 6° for the 450 µg group. Over the same time frame, the placebo group showed no change in knee ROM.
- At day 120 and 180, post-hoc analysis showed that the change in knee ROM was statistically significant between the placebo and 450-µg group (p=0.042 and 0.022, respectively).
- We have previously shown that increased knee flexion ROM following total knee replacement is positively associated with improvements in daily physical activity levels.1 Therefore, improvements in knee flexion ROM in this analysis could have a positive impact on physical activity levels as well.
Walking speed
- All groups appeared to increase their walking speed from baseline with small to large effect sizes noted (0.05-0.13 m/s [Cohen’s d = 0.24-1.1]). However, there were no statistically significant differences in walking speed from baseline at any of the time points.
- Importantly, almost 27% of the participants allocated to the 450 µg group increased their walking speed to exceed 1.3 m/s by day 180 (1/23 to 7/23 patients). The threshold of 1.3 m/s is important as it has been suggested to be the speed required to cross a road safely.2
1 Arnold, J. B., Mackintosh, S., Olds, T. S., Jones, S., & Thewlis, D. (2015). Improvements in knee biomechanics during walking are associated with increased physical activity after total knee arthroplasty. Journal of Orthopaedic Research, 33(12), 1818-1825.
2 Middleton, A., Fritz, S. L., & Lusardi, M. (2015). Walking speed: the functional vital sign. Journal of aging and physical activity, 23(2), 314-322.
About Xalud Therapeutics
Xalud Therapeutics is a clinical-stage biotechnology company advancing a non-viral plasmid DNA (pDNA)-delivered gene therapy platform to treat pathologic inflammation by restoring homeostasis in the immune system. Xalud’s initial approach is focused on harnessing the power of interleukin-10 (IL-10), a potent cytokine that acts as a master regulator for multiple inflammatory pathways, to address the root cause of inflammation in several chronic inflammatory indications with a high unmet need. This includes programs in both musculoskeletal and neurodegenerative diseases. Xalud’s lead candidate, XT-150, is a patent-protected, locally injectable pDNA-delivered gene therapy expressing IL-10v, a proprietary modified version of IL-10.
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