An extension of a Phase 2/3 study testing Actemra (tocilizumab) in patients with systemic sclerosis (SSc) found that skin involvement improved with 48 additional weeks of treatment. A Phase 3 trial looking to confirm these results is now underway.
Trial results, were published in the study “Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)” in the journal Annals of the Rheumatic Diseases.
Actemra, marketed by Genentech, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, and giant cell arteritis.
The faSScinate trial (NCT01532869) included 87 SSc patients and conducted in two parts. During its 48-week, initial double-blind period, 44 patients received placebo and 43 patients were given weekly injections of tocilizumab at 162 mg.
During the open-label period that followed, both groups received the treatment. A total of 51 patients completed week 96: 24 (54.5%) from the original placebo group and 27 patients (62.8%) from the treatment group were given Actemra for a second period of 48 weeks.
The primary endpoint was improvement in the modified Rodnan Skin Score (mRSS), a measure of skin disease in SSc.
Changes in forced vital capacity (FVC) — the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible — was also assessed to find if Actemra worked to arrest progression of lung involvement in SSc. FVC is used to help determine both the presence and severity of lung diseases.
Results showed that the mRSS dropped by an average of 9.4 points at week 96 in patients who switched from placebo to Actemra, and by an average of 9.1 points among those on continuous Actemra treatment in both studies.
“Patients originally assigned to receive placebo in the double-blind period who transitioned to open-label tocilizumab at week 48 experienced improvements in mRSS by week 96 that were similar to those of patients who received tocilizumab throughout the study,” the researchers wrote.
No patient had more than a 10% decline in FVC.
Infections were the most frequently reported and serious side effect seen. An increased rate of serious infections was observed after patients transitioned from placebo to treatment, but they occurred less frequently in those using Actemra over the longer term, the team reported. These side effects included infected skin ulcers, pneumonia and osteomyelitis (bone infection).
“Results from the open-label period of the faSScinate trial suggest that treatment with tocilizumab is associated with benefits for skin fibrosis, lung fibrosis and physical function in patients with SSc but increased the risk for serious infections. Tocilizumab may be a promising targeted therapy for patients with progressive SSc who have few treatment options,” the study concludes.
“Further studies are required to investigate the efficacy and safety of tocilizumab in the treatment of patients with SSc and to determine whether tocilizumab produces significant improvement in skin sclerosis and stabilisation of lung function,” researchers added.
A double-blind, Phase 3 trial (NCT02453256), called focuSSced, offering treatment for a total of 96 weeks including in an open-label extension period, is ongoing to further evaluate Actemra in some 200 SSc patients. This study is expected to conclude in February 2019.