Kiniksa launches Phase 2b clinical trial of abiprubart in Sjögren’s
Trial designed to evaluate therapy's effects on disease severity
Kiniksa Pharmaceuticals has launched a Phase 2b clinical trial to test its injectable therapy abiprubart against a placebo in people with Sjögren’s syndrome.
The trial, mainly designed to assess the treatment’s effects on disease severity, is expected to involve about 201 Sjögren’s patients. Kiniksa reports that the trial has started enrolling, but no recruitment information was provided.
“Sjögren’s disease is a debilitating, chronic autoimmune disorder currently with no FDA [U.S. Food and Drug Administration]-approved therapies,” Sanj K. Patel, chairman and CEO of Kiniksa, said in a company press release. “Commencing the next phase of development of abiprubart in Sjögren’s disease is an important step forward for patients.”
The trial will be double-blind, meaning that neither researchers nor participants will know which patients are receiving the experimental treatment and which the placebo.
Phase 2b clinical trial to test abiprubart as injectable therapy
In Sjögren’s syndrome, the immune system mistakenly launches inflammatory attacks on the body’s own healthy moisture-producing glands, such as the salivary and tear glands.
No treatments have yet been approved in the U.S. for the rare disease, whose symptoms include chronically dry eyes and mouth, joint pain, fatigue, and damage to other organs.
Previously known as KPL-404, abiprubart is an antibody-based therapy designed to bind to the CD40 protein and inhibit its interaction with another protein called CD154, also known as CD40L. Coupling of these two proteins mediates the immune cell interactions that drive autoimmune activity in Sjögren’s and other conditions.
By blocking it, Kiniksa believes abiprubart will help dampen this aberrant immune activity and ease disease symptoms.
A couple other investigational therapies target CD40 or CD154 signaling. Among them are Amgen’s dazodalibep, a fusion protein that blocks CD154, and Novartis’ iscalimab, an antibody that blocks CD40. Clinical trial data on those molecules offers proof-of-concept for abibrubart’s mechanism, according to Kiniksa. Both have been found to ease disease activity in Sjögren’s patients.
Abiprubart already has been tested in a Phase 1 trial (NCT04497662) involving healthy volunteers. In that study, both intravenous, or into-the-vein, and subcutaneous, or under-the-skin, dosing was well tolerated and showed evidence of effective immune suppression. Kiniksa believes the opportunity for subcutaneous dosing might offer more convenience for patients.
In people with rheumatoid arthritis, another autoimmune condition, abiprubart was found to ease disease severity and reduce inflammation in a Phase 2 trial (NCT05198310).
In the newly launched Phase 2b trial for Sjögren’s, patients will be randomly assigned to receive subcutaneous injections of abiprubart, at a 400 mg dose, or a placebo. The injections will be given once every two weeks or once per month, for 24 weeks, or about six months.
This Phase 2b clinical trial builds on external mechanistic proof-of-concept as well as learnings from our own prior clinical data.
The main goal is to evaluate changes in disease severity, as assessed by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) after six months. Other disease severity assessments will also be conducted as secondary endpoints.
After the main part of the trial, participants will be able to enter a long-term extension period in which all will receive abiprubart for another six months.
“This Phase 2b clinical trial builds on external mechanistic proof-of-concept as well as learnings from our own prior clinical data,” Patel said.
Kiniksa noted that the clinical development program for abiprubart in Sjögren’s is fully funded.
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