Scientists dose first patient in trial of targeted kidney treatment for IgAN
Injection drug showed promising results when given to healthy volunteers
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A clinical trial testing an injection therapy for IgA nephropathy is now enrolling patients at a single study site in China. (Image from iStock)
In a large clinical trial testing CLYM116, an injection therapy for people with IgA nephropathy (IgAN), dosing of adults with the chronic kidney condition is now underway, its developer announced.
Initial data from the China-based Phase 2 trial, dubbed NAVIGATE-2 (NCT07375758), are anticipated by June. The study is now enrolling individuals 18 and older, with a biopsy-confirmed diagnosis of IgAN and active kidney damage, at a single site in the Asian nation.
Climb Bio, which holds an exclusive license from Beijing Mabworks Biotech to develop and commercialize CLYM116 outside of greater China, is also planning to launch — next year — a global Phase 3 study to further evaluate the experimental therapy in IgAN patients, according to a company press release announcing its latest financial results and business updates.
Meanwhile, CLYM116 demonstrated promising results in healthy volunteers in the Phase 1 portion of NAVIGATE and in a second complementary Phase 1 study (NCT07248865) in Australia, according to the developer.
The company reported that, across both studies, a single dose of CLYM116 was generally well tolerated and nearly completely suppressed its intended protein target, known as APRIL, over about three months.
“For CLYM116, two independent datasets support a best-in-class anti-APRIL profile,” said Aoife Brennan, president and CEO of Climb Bio.
IgA nephropathy is characterized by an abnormal form of the IgA antibody, galactose-deficient IgA1 (Gd-IgA1), which clumps together inside the kidney’s filtration units, called glomeruli. This leads to inflammation and kidney damage.
Despite the condition’s rarity, it remains one of the leading causes of kidney disease and kidney failure.
Injection treatment aims to block disease-driving protein in IgAN
CLYM116 is designed to block APRIL — fully, A proliferation-inducing ligand — a protein that promotes the survival of plasma cells, the immune cells that produce large amounts of antibodies, including those that drive the disease. By suppressing APRIL, the therapy is expected to kill plasma cells and reduce harmful antibody production, thereby slowing IgAN progression and easing symptoms.
The two complementary Phase 1 studies enrolled 42 and 46 healthy adult volunteers in China and Australia, respectively. Both evaluated the safety, tolerability, and pharmacological properties of increasing single doses of CLYM116, given as a subcutaneous, or under-the-skin, injection compared with a placebo.
Data from both studies showed that blood levels of the drug increased proportionally with the dose amount across the effective dose range. The drug was also cleared from the body in a predictable manner, per the developer.
At a single dose of at least 480 mg, CLYM116 suppressed APRIL by more than 90% for 12 weeks. After a single 800 mg dose, the therapy lowered blood levels of IgA by about 60% and Gd-IgA1 by about 70% at the same three-month mark. Together, these data support a 12-week dosing regimen, Climb Bio stated in its release.
CLYM116 was generally well tolerated, with no treatment-related serious adverse events, dose-limiting toxicities, or abnormally low antibody levels, known as hypogammaglobulinemia.
Treatment to be given every 8 or 12 weeks after first dose
The Phase 2 portion of NAVIGATE-2 is now testing CLYM116 in adults with a definitive IgAN diagnosis confirmed by kidney biopsy, in which a small tissue sample is collected and analyzed under a microscope.
Eligible participants must also show signs of active kidney damage, as indicated by high protein levels in the urine, and be on a stable regimen of standard kidney-protective blood pressure medications. However, participants’ blood work must show acceptable organ function to tolerate the investigational drug.
Participants receive an 800 mg loading dose of CLYM116, followed by a 400 mg dose every eight weeks (about two months), or every 12 weeks. This dosing is intended to support advancement to an every 12-week regimen in a potentially upcoming Phase 3 trial. Patients will be followed for as long as 18 months, or about 1.5 years, after enrollment.
The main goals of the Phase 2 portion are to assess changes in blood levels of Gd-IgA1 after 12 weeks and urine protein levels after 24 weeks, or about six months.
In addition to IgAN, the company said CLYM116 is being advanced for the treatment of other plasma cell-mediated diseases in which APRIL plays a role.
