Treatment with the investigational vaccine IFN-alpha Kinoid increased the number of systemic lupus erythematosus (SLE) patients achieving low disease activity, lessened their use of corticosteroids, and was well-tolerated, according to full results of a Phase 2b trial.
The findings, “IFN Kinoid in Systemic Lupus Erythematosus (SLE): Results from a Phase IIb, Randomized, Placebo-Controlled Study,” were presented at the 13th International Congress on Systemic Lupus Erythematosus (LUPUS 2019) by Frédéric Houssiau, MD, PhD, a professor at the Université Catholique de Louvain in Belgium, and the chairman of the trial.
People with SLE experience a higher-than-normal production of a molecule called IFN-alpha, which boosts autoimmune responses. The experimental vaccine, developed jointly by Neovacs and Centurion Pharma, was designed to block all 13 subtypes of IFN-alpha, using a technology called Kinoid that primes the patient’s immune system to produce antibodies, or blood proteins, that counteract this molecule.
The double-blind, placebo-controlled study (NCT02665364) assessed the effectiveness and safety of IFN-alpha Kinoid in patients with active SLE on standard-of-care therapy. A total of 185 adults with moderate-to-severe disease activity were enrolled in the study, conducted in Europe, Asia, U.S., North Africa, and Latin America.
Patients received either the vaccine or a placebo, given through five injections into the muscle on days one, seven, and 28, and then at three and six months. They also received standard treatment with antimalarials, immunosuppressants, or steroids; the steroids were progressively reduced through 24 weeks, with the dose then remaining stable until week 36.
The trial was designed primarily to analyze the vaccine’s biological and clinical effectiveness at nine months, or 36 weeks, after the first dose. Secondary goals were determining other disease activity measures and safety.
Results showed that treatment with IFN-alpha Kinoid caused production of anti-IFN-alpha antibodies in 72 of 79 patients (91.4%). The vaccine also led to a trend toward better scores on the SRI-4 measure of disease activity on patients, with corticosteroid reduction to 5 mg per day or less. This became statistically significant in treated patients who developed anti-IFN alpha antibodies.
Findings also showed more of those treated with IFN-alpha Kinoid achieved low disease activity (52.9%) compared to patients given the placebo (29.8%), as assessed by the Lupus Low Disease Activity State (LLDAS) score. However, as previously reported, no significant changes were seen in clinical response measured by the BILAG Based Combined Lupus Assessment (BICLA).
Patients on the vaccine also used less corticosteroids at 36 weeks – 5.4 mg vs. 7.1 mg in the placebo group – and showed less fatigue.
IFN-alpha Kinoid was well-tolerated, with no difference in rates of non-serious adverse events, treatment-emergent adverse events, and treatment-related adverse events compared to the placebo. One severe infection occurred in the IFN-alpha Kinoid group, and one death occurred in each group.
Serious adverse events were more common in people on placebo (12.9%) than on IFN-K (6.6%). Most were related to the disease, and to a local reaction at the injection site.
At the end of this primary evaluation, the participants entered a five-year follow-up period to determine the long-term safety, and biological and clinical efficacy, of IFNα Kinoid.
Overall, these positive results “merit further evaluation in a phase 3 study,” the scientists concluded.
Houssiau, the trial’s chair, mentioned the “significant biological effect” of IFN-alpha Kinoid in a press release. He said the results in SRI-4 were “encouraging,” despite the lack of benefits seen in the BICLA score. Houssiau also underlined the importance of the LLDAS score findings.
“According to the world’s lupus experts, [it] may become the main criteria to assess disease activity and response to treatment when submitting applications to regulatory agencies,” he said.
Houssiau added that the lower use of corticosteroids “may eventually lead to a major breakthrough, as it could improve the patients’ quality of life considerably by eliminating [their] adverse effects.”