Clinical trial recruitment for povetacicept ongoing in 3 countries

RUBY-3 Phase 1b/2a study seeking AAV patients, others, with kidney issues

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Recruitment is continuing in three countries for a Phase 1b/2a clinical trial testing Alpine Immune Sciences’ povetacicept in adults with autoimmune conditions affecting the kidneys, including ANCA-associated vasculitis (AAV).

Called RUBY-3 (NCT05732402), the early study is designed to enroll an estimated 56 patients, ages 18 and older, with autoimmune glomerulonephritis, or inflammation of the kidney’s filtering units. The study is being conducted at multiple clinical sites in the U.S., Australia, and the Republic of Korea, according to a company press release.

Eligible AAV patients must test positive for one of the two most common self-reactive antibodies, or autoantibodies, driving the disease — those targeting either the proteinase 3 or myeloperoxidase enzymes — and have confirmed kidney involvement. Patients being treated to induce disease remission must have started treatment at least four weeks before enrolling.

The other three eligible diagnoses for autoimmune glomerulonephritis include immunoglobulin A (IgA) nephropathy, primary membranous nephropathy, and lupus nephritis, a common complication of systemic lupus erythematosus.

“In addition to updates on our clinical studies, we look forward to sharing translational data that further supports the best-in-class potential of povetacicept in multiple inflammatory diseases,” Mitchell H. Gold, MD, Alpine’s executive chairman and CEO, said in a corporate update and reporting of 2023 financial results.

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Povetacicept was well tolerated in healthy volunteers

In the human body, B-cells are a type of immune cells that produces antibodies to help fight infections. But in autoimmune conditions such as AAV, some of these antibodies wrongly attack the body’s own tissues, causing tissue and organ damage.

Povetacicept, also known as ALPN-303, is designed to block two targets simultaneously for a potentially enhanced therapeutic effect. Its targets are BAFF and APRIL, two proteins that help B-cells live longer and become activated to produce antibodies.

As such, the therapy, delivered through subcutaneous or under-the-skin injections, is expected to help reduce autoimmune responses — ultimately lessening organ damage and disease symptoms.

In the placebo-controlled Phase 1 RUBY-1 trial (NCT05034484), which involved 66 healthy adult volunteers, subcutaneous injections of povetacicept — at doses ranging from 80 to 240 mg — were found to be well tolerated. The most frequent side effect was mild headache.

Data also showed that the therapy led to dose-dependent reductions in the levels of circulating antibodies and antibody-producing B-cells.

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Recruitment for clinical trial continues in 9 US states

The Phase 1b/2a RUBY-3 study, which started a year ago, is assessing the safety, pharmacological properties, and efficacy of two doses of povetacicept (80 or 240 mg) in adults with AAV and other causes of autoimmune glomerulonephritis.

Participants receive the therapy every four weeks for six months, after which they may choose to continue treatment for an additional six months in the study’s extension period. Those completing the 1-year treatment period may be offered the possibility to continue the therapy for up to an additional year.

Besides safety, the trial’s key goals include changes in several markers of kidney function, including protein levels in urine and the estimated glomerular filtration rate (eGFR), as well as levels of disease-related autoantibodies.

Early trial data from 12 IgA nephropathy participants, presented at a conference late last year, showed that multiple dosing of 80 mg of povetacicept for six months safely and effectively led to pronounced reductions in urine protein levels and eGFR stabilization, indicating better kidney function.

Moreover, low-dose treatment also led to drops in the levels of several types of antibodies — but did not cause severe deficiency of IgG antibodies, which could place patients at risk for infection. Also, there were no reports of treatment-related side effects.

We are rapidly advancing development of povetacicept as a potentially meaningful new therapeutic option for patients living with … autoantibody-related diseases.

Recruitment for the clinical trial is continuing in several U.S. states: Arizona, California, Colorado, Florida, Massachusetts, New Jersey, New York, Pennsylvania, and Texas. Three sites across Australia also are enrolling patients, as are eight in Korea. The trial is expected to run through the beginning of 2026.

“With our encouraging data set in IgAN [IgA nephropathy], convenient once monthly dosing regimen, and strong balance sheet, we are rapidly advancing development of povetacicept as a potentially meaningful new therapeutic option for patients living with IgAN, systemic lupus erythematosus (SLE), and multiple other autoantibody-related diseases,” Gold said.