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Safety and Efficacy of Lenabasum in a Phase II, Randomized, Placebo‐Controlled Trial in Adults With Systemic Sclerosis
Author(s) -
Spiera Robert,
Hummers Laura,
Chung Lorinda,
Frech Tracy M.,
Domsic Robyn,
Hsu Vivien,
Furst Daniel E.,
Gordon Jessica,
Mayes Maureen,
Simms Robert,
Lafyatis Robert,
Martyanov Viktor,
Wood Tammara,
Whitfield Michael L.,
Constantine Scott,
Lee Elizabeth,
Dgetluck Nancy,
White Barbara
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41294
Subject(s) - placebo , medicine , randomized controlled trial , adverse effect , gastroenterology , rheumatology , surgery , pathology , alternative medicine
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.