Vilobelimab Safe, Well-tolerated in Phase 2 IXPLORE Study

Adding vilobelimab (IFX-1) to standard of care treatment is safe and well-tolerated among patients with ANCA-associated vasculitis (AAV), according to top-line results from the ongoing Phase 2 IXPLORE study.

Some participants also showed clinical response and remission, although the study was not designed to assess the statistical significance of such findings.

“We are pleased to report that vilobelimab was safe and well tolerated in combination with standard of care for patients with ANCA-associated vasculitis in the U.S. IXPLORE Phase II trial,” Korinna Pilz, MD, global head of clinical research and development for InflaRx, vilobelimab’s developer, said in a press release.

Vilobelimab is designed to limit the excessive inflammatory response that AAV patients experience. It works by blocking the activity of the C5a protein, which plays a key role in activating the complement system. The complement system is an arm of the body’s immune system that grows overactive in AAV.

The U.S. study (NCT03712345) is comparing two vilobelimab dose regimens with a placebo in 19 adults with active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

The participants were randomly assigned to receive either 400 mg vilobelimab, 800 mg vilobelimab, or a placebo, twice weekly, while continuing their standard-of-care immunosuppressive therapy and high-dose glucocorticoids. In all, seven patients were given the 400 mg dose, while six received the 800 mg dose, and six were given the placebo.

Treatment lasted for 16 weeks (about four months), followed by an eight-week safety observation period.

An analysis found the treatment to be safe and well-tolerated.

While a majority of patients on the placebo and vilobelimab experienced an adverse event, drug-related side effects were more common in the placebo group (50% vs. 38%), and all side effects reflected either AAV itself or standard treatment.

Efficacy data also demonstrated some effectiveness. At the end of the 16-week treatment period, most patients in the three groups responded to treatment — defined as a 50% reduction in Birmingham Vasculitis Activity Score (BVAS), which measures disease activity.

Yet, a greater proportion of patients on vilobelimab achieved remission, compared with those given a placebo. At the final visit, conducted after 24 weeks (about six months), 80% of patients in the high dose achieved remission, compared with 71.4% of those in the low dose, and 50% of patients on placebo.

The company plans to present more detailed results at an upcoming medical meeting.

“Although current treatments for AAV are quite helpful in many patients, there are still unmet needs for fast-acting, effective, and safe treatments and alternatives to the regular use of high-dose glucocorticoids,” said Peter A. Merkel, MD, chief of rheumatology at the University of Pennsylvania.

“The results of the IXPLORE trial show C5a blockade by vilobelimab is safe and well tolerated when added to standard of care therapy for AAV,” Merkel said.

“These results support the continued study of vilobelimab for the treatment of AAV,” he added.

InflaRx also is evaluating vilobelimab in a separate Phase 2 study (NCT03895801) taking place in Europe and dubbed IXCHANGE. That trial completed enrollment earlier this year.

“We are looking forward to our EU IXCHANGE Phase 2 trial results later this year where we are further evaluating the potential efficacy of vilobelimab alone compared to a standard dose of glucocorticoids,” Pilz said. “The results from these two trials will provide us good insight to plan our next development steps in this important indication.”