KU School of Medicine testing new drug to treat inherited form of kidney disease

Researchers at the University of Kansas School of Medicine are taking part in a multi-site clinical trial testing a new drug to treat a serious type of chronic kidney disease (CKD) caused by an inherited damaged gene.

Healthy kidneys remove waste and excess fluid from the blood. These waste products then exit the body via urine. When CKD impairs this process, proteins can escape from the blood into the urine, a condition known as proteinuria, and waste builds up in the body. People with CKD may develop high blood pressure, heart problems, nerve damage and other issues. Ultimately, the disease leads to kidney failure, and patients need dialysis or a transplant to live.

More than 1 in 7 adults in the United States have CKD, according to the National Kidney Foundation. There are different types of CKD. A particularly progressive form is caused by an inherited mutation in the APOL1 (apolipoprotein L1) gene, which causes the gene to produce a rogue variant of the APOL1 protein that can damage the kidneys. A new investigational drug compound called inaxaplin, which is produced by Vertex Pharmaceuticals, is being tested in this clinical trial to see if it can inhibit the function of this harmful protein and slow or stop the progression of the disease.

“Right now, there are no treatments specifically for APOL1-mediated kidney disease,” said Kelly Liang, M.D., associate professor of nephrology and hypertension and principal investigator for the clinical trial site at KU School of Medicine. “Currently, treatment may consist of general blood pressure medications that are used for other proteinuric kidney diseases. However, the agent being investigated is specifically targeted toward this APOL1 mutation, the underlying cause, to see if it may be more effective.”

Moving the science

The mutated APOL1 gene is more likely to occur in people of African ancestry, which includes people who identify as African American, Black, Caribbean, Sub-Saharan African and Latino (Cuban, Mexican, Puerto Rican or South or Central American).

“With this trial, the science moves beyond just saying, ‘among people from African descent, there is increased risk,’” noted Reem Mustafa, M.D., Ph.D., MPH, professor of nephrology and hypertension at KU School of Medicine and director of the Evidence-based Practice and Impact Center (EPIC). “We're trying to understand why this mutation specifically increases the risk, and (we want) to identify and evaluate targeted therapies for this specific form of CKD, and that’s what we’re investigating.”

The study

The clinical trial, known as AMPLITUDE, aims to test the effectiveness, at different dosages, of inaxaplin in people who are 18 to 60 years of age and have APOL1-mediated CKD.

Potential participants undergo genetic screening to confirm they have the mutation. Those who have the mutation and qualify for the AMPLITUDE study are randomized into three groups: those receiving a 15 mg daily dose of the drug, those receiving a 45 mg daily dose and the control group, who does not get the drug.

The drug’s effectiveness will be measured by how much it reduces the level of protein in the urine and how it affects kidney function, measured by the kidneys’ ability to filter waste from the blood. Once the study teams have determined which dosage is most effective, they plan to expand the study to test that dose in more participants. The trial is expected to last four years.

“Most of these patients have progressive disease, so we really need a better treatment option,” said Liang.