Phase 2 Trial of CellCept Plus Esbriet for SSc-ILD Enrolling in US

The Scleroderma Lung Study III (SLSIII), a Phase 2 clinical trial of oral CellCept (mycophenolate mofetil) alone or in combination with Esbriet (pirfenidone) in  scleroderma-associated interstitial lung disease (ILD) is enrolling patients.

The trial (NCT03221257) is taking place across 17 clinical sites in the U.S., including the University of California Los Angeles (UCLA), the study’s lead institution in collaboration with the University of Michigan.

Enrollment will be open through Oct. 1. More information on locations and contacts can be found here.

Among other criteria, eligible adults must have shortness of breath and poorer lung function, and must not have taken CellCept or other therapies over more than six months prior to the study.

Esbriet, by Genentech, is an approved oral therapy for people with idiopathic pulmonary fibrosis (IPF), a disease characterized by progressive scarring (fibrosis) in the lungs that compromises their ability to function, as seen in patients with scleroderma, or systemic sclerosis (SSc)-ILD. The medication has shown an ability to rapidly slow disease progression and delay loss of lung function in people with IPF.

Researchers at UCLA hypothesized that the rapid anti-scarring effects of Esbriet may complement the anti-inflammatory and immunosuppressive effects of CellCept, leading to greater lung function improvements in patients with SSc-ILD compared to CellCept alone.

CellCept is an immunosuppressant that inhibits the differentiation of fibroblasts into myofibroblasts to potentially ease fibrosis, and is often used to treat people with SSc-ILD or rapidly progressive diffuse cutaneous scleroderma.

SLSIII will randomly assign 150 patients to receive either CellCept plus Esbriet or CellCept and a placebo (control group) for 18 months. CellCept will be given in doses up to 1,500 mg twice daily, and Esbriet in an up to 801 mg dose taken three times daily. The trial is being conducted in collaboration with Genentech.

The study’s main goal is to assess lung function as measured by forced vital capacity — the total amount of air a person is able to exhale after taking a deep breath — over the 18 months of treatment (in three-month intervals).

Additional goals include measuring the diffusing capacity for carbon monoxide, or the ability of the lungs to transfer oxygen from their air sacs to the blood; the modified Rodnan skin score, a measure of skin thickness; and patient-reported outcomes, including changes in shortness of breath and the St. George’s Respiratory Questionnaire on quality of life.

SLSIII is the third of related studies, following the SLSI and SLSII trials. While SLSI (NCT00004563) assessed the effects of Cytoxan (cyclophosphamide), SLSII (NCT00883129) compared treatment with CellCept to Cytoxan on lung function and health-related symptoms in patients with SSc-ILD.

SLSI found that Cytoxan was superior to a placebo in easing shortness of breath and skin thickness, but benefits in lung function and physical function were not as durable.

Results from the SLSII trial showed that oral treatment over two years with CellCept and cyclophosphamide led to clinically meaningful improvements in perceived health status and function, while also easing shortness of breath in SSc‐ILD patients.

“The first two scleroderma lung studies established that scleroderma-related interstitial lung disease is a treatable condition, and that it can be treated with medications that are relatively well tolerated,” Michael Roth, MD, pulmonologist and principal investigator of SLSIII, said on the trial’s webpage.

“With SLS III we’re testing a novel therapy to be used along with the standard therapy to see if the combination can offer additional benefits,” added Sam Weigt, MD, pulmonologist and director of the UCLA Interstitial Lung Disease Center.

SSc‐ILD patients with clinically significant pulmonary hypertension are not eligible to participate in SLSIII, which is expected to fully finish in June 2022.