Safety and Efficacy of Lenabasum in a Phase II, Randomized, Placebo‐Controlled Trial in Adults With Systemic Sclerosis

Abstract

Objective To assess the safety and efficacy of lenabasum in diffuse cutaneous systemic sclerosis (dc SS c). Methods A randomized, double‐blind, placebo‐controlled, phase II study was conducted at 9 SS c clinics in the US . Adults with dc SS c of ≤6 years’ duration who were receiving stable standard‐of‐care treatment were randomized to receive lenabasum (n = 27) or placebo (n = 15). Lenabasum doses were 5 mg once daily, 20 mg once daily, or 20 mg twice daily for 4 weeks, followed by 20 mg twice daily for 8 weeks. Safety and efficacy were assessed at weeks 4, 8, 12, and 16. Results Adverse events ( AE s) occurred in 63% of the lenabasum group and 60% of the placebo group, with no serious AE s related to lenabasum. Compared to placebo, lenabasum treatment was associated with greater improvement in the American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis ( CRISS ) score and other efficacy outcome measures that assessed overall disease, skin involvement, and patient‐reported function. The median CRISS score increased in the lenabasum group during the study, reaching 0.33, versus 0.00 in the placebo group, at week 16 ( P = 0.07 by 2‐sided mixed‐effects model repeated‐measures analysis). Gene expression in inflammation and fibrosis pathways was reduced, and inflammation and fibrosis were improved on histologic evaluation of skin biopsy specimens, in the lenabasum group compared to the placebo group (all P ≤ 0.05). Conclusion Despite a short trial duration in a small number of patients in this phase II study in dc SS c, our findings indicate that lenabasum improves efficacy outcomes and underlying disease pathology with a favorable safety profile.

Molecular Mechanisms for the Inflammation-Resolving Actions of Lenabasum

“…Likewise, the clinical trial findings do not support this assumption (Karst et al, 2003) ( Salim et al, 2005) (Karst, 2007) (Spiera et al, 2020).…”

Considerations for a combined index for limited cutaneous systemic sclerosis to support drug development and improve outcomes

“…Most importantly, the CRISS was designed as an assessment tool for dcSSc and was validated using data from randomized clinical trials (RCTs) of patients with early dcSSc and paper patients from longitudinal cohorts of dcSSc (37). Nonetheless, the ACR CRISS and its use it recent RCTs serves as proof of concept that a global assessment of SSc is possible, and potential candidates of disease-modifying drugs can be evaluated using such a tool, even in short term trials with limited sample sizes (36,38). This is especially true considering that in some cases the ACR CRISS can successfully differentiate active therapy vs. placebo, when the primary outcome measure fails to do so, such as in the abatacept trial (31).…”

“…This ACR-endorsed combined response index for systemic sclerosis (CRISS) was designed to capture the global improvement of dcSSc based on the selection of domains and items in accordance with the outcome measure in rheumatology (OMERACT) strategy. 46 The ACR CRISS has been shown to differentiate active therapy versus placebo in recent phase II trials 42,47 and has been utilized as an acceptable endpoint for registration trials. This combined response index is based on a two-step evaluation.…”

Current therapy of interstitial pneumonia associated with systemic scleroderma

“…в РКИ II фазы у больных с диффузной формой ССД (n=42). Предварительные результаты свидетельствуют о положительной динамике проявлений у лиц, получавших Lenabasum [51]. Lenabasum -это малая молекула, которая избирательно связывается в качестве агониста с каннабиноидным рецептором типа 2 (CB2).…”