A PHASE 3 TRIAL OF THE EFFICACY AND SAFETY OF BARDOXOLONE METHYL IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Protocol No: 402-C-1808, WCG Protocol #20190922
Sponsor: Reata Pharmaceuticals, Inc.
Investigator: Kianoosh Kaveh, DO
You may be eligible for this study if you:
Are 18 to 70 years of age
Have been diagnosed with ADPKD
About Bardoxolone methyl
Bardoxolone methyl is a capsule taken by mouth that has been tested in many clinical studies with different diseases.
In prior trials, bardoxolone methyl has consistently improved parameters of kidney function in some patients with CKD, cancer, and pulmonary hypertension. Research completed to date suggests that bardoxolone methyl may:
Decrease inflammation in the kidney, protect the kidney from injury, and prevent fibrosis (changes in the structures) within the kidney, based on data from animal models
Significantly increase glomerular filtration rate (GFR) in patients with diabetic kidney disease, Alport syndrome, IgA nephropathy, and autosomal dominant polycystic kidney disease
Produce GFR increases that are sustained for at least one year, with a portion of the increase retained 4 weeks after stopping treatment, in patients with diabetic kidney disease and Alport syndrome
Overall, bardoxolone methyl has been well tolerated in clinical trials. The most common side effects have included muscle cramps and nausea. A previous large study in over 2000 diabetic patients with severe, stage 3 and 4 chronic kidney disease was stopped early because bardoxolone methyl increased the risk for fluid retention in a subset of patients who had previously been hospitalized for heart failure and who had fluid retention prior to the start of the study.
The increased risk for fluid retention was only observed in the first month after starting treatment. The identified risk factors are now used to exclude patients who are more likely to retain fluid from participating in studies with bardoxolone methyl. To date, bardoxolone methyl has not been shown to increase the risk for fluid retention in subsequent studies, including those in diabetic chronic kidney disease, pulmonary arterial hypertension, Alport syndrome, IGA nephropathy, and autosomal dominant polycystic kidney disease patients.
FALCON will exclude patients with stage 4 chronic kidney disease and these risk factors. Additionally, patients will be monitored closely during the first two months of the trial to ensure they do not develop fluid retention.
How Might Bardoxolone Methyl Treat AKPKD
Your glomerular filtration rate (GFR) is an estimate of how well your kidneys are working. In patients with ADPKD, genetic mutations in PKD1 and PKD2 genes leads to the formation of fluid-filled cysts in the kidneys and other organs. The cysts continue to grow and can cause the kidneys to expand up to five to seven times their normal volume, leading to pain and progressive loss of kidney function (and causes decrease in GFR).
As in other forms of CKD, decreased mitochondrial function and chronic inflammation are key drivers of disease progression in ADPKD. Decreasing GFR ultimately results in the need for dialysis or kidney transplant. In July 2018, Reata released 12-week data from PHOENIX, a Phase 2 study for patients with rare kidney diseases, for the ADPKD portion of the study. PHOENIX enrolled 31 ADPKD patients. Key observations from this patient population included the following:
Historical eGFR data from 29 of these patients showed their kidney function was declining at an average annual rate of 4.8 mL/min/1.73 m2 for three years prior to participating in the study
Significant eGFR increase of 9.3 mL/min/1.73m2 was seen after 12 weeks of treatment
Bardoxolone methyl was well-tolerated without any evidence of fluid overload. The most common side effect was muscle cramps
Data suggest that long-term eGFR improvements and retained eGFR benefit observed in other forms of CKD may translate to patients with ADPKD
In previous studies in patients with diabetes and chronic kidney disease, bardoxolone methyl produced an increase in estimated GFR (eGFR) that was sustained for 1 year in some patients. It is not known whether an increase in eGFR, if achieved, will provide long-term benefit in patients with ADPKD. Consequently, FALCON is designed to test the effects of bardoxolone methyl on eGFR in patients with ADPKD through 2 years of treatment.
Have been diagnosed with ADPKD
Before participating in FALCON, patients must complete two screening visits at one of the study centers. Eligible patients will receive either bardoxolone methyl or placebo (an inactive capsule). Patients will be randomly assigned (like by the flip of a coin) to either bardoxolone methyl or placebo. The group of patients assigned to bardoxolone methyl will be compared to the group of patients assigned to placebo in order to help researchers better understand the effects of bardoxolone methyl. The study team will follow all patients closely throughout study participation.
All participants will follow the same visit schedule and will be asked to complete the same study procedures. Participation in FALCON is planned to last up to 2 years and will include about 20 study visits and 6 scheduled phone calls.
The investigational drug, study-related procedures, and doctor visits will be provided at no cost. If you travel to the site for your study visits, travel expenses will be reimbursed, and compensation for study-related time may be provided.
Protection for Falcons Participants
The ethics and laws that govern medical practice also apply to clinical studies. A process called informed consent ensures you know all the facts regarding the study (including potential side effects), the investigational drug, and your condition.
If you decide to participate, you will sign an informed consent document. This document is not binding, and you may withdraw from the study at any time, for any reason.