Atrasentan for IgA Nephropathy
(ASSIST Trial)
Recruiting in Palo Alto (17 mi)
+34 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Chinook Therapeutics, Inc.
Must be taking: RAS inhibitors, SGLT2 inhibitors
Must not be taking: Systemic immunosuppressants
Disqualifiers: Chronic kidney disease, Transplantation, Hypertension, Heart failure, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing atrasentan, a medication for people with IgA nephropathy (IgAN) who are already on standard treatments. It works by blocking pathways that cause kidney damage, aiming to lower protein levels in the urine. Atrasentan has been previously tested for its effects on albuminuria reduction in patients with type 2 diabetes and nephropathy.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of a RAS inhibitor and an SGLT2 inhibitor before joining. If you are taking other investigational or certain immunosuppressive medications, a washout period (time without taking these medications) may be required.
Is atrasentan safe for human use?
Atrasentan has been studied for various conditions, including prostate cancer and diabetic nephropathy. Common side effects include peripheral edema (swelling), rhinitis (runny nose), headache, and heart failure. In diabetic nephropathy studies, it was generally safe but associated with fluid retention, especially at higher doses.
12345Eligibility Criteria
Adults with IgA Nephropathy who have significant protein in their urine can join this trial. They must be on stable doses of specific kidney medications and agree to use effective contraception. Excluded are those with heart failure, other chronic kidney diseases, recent cancer (except certain skin or cervical cancers), blood pressure issues, severe liver disease, organ transplants, or recent immunosuppressant use.Inclusion Criteria
I have been on a stable, high dose of blood pressure medication for at least 12 weeks.
Your kidney function, measured by eGFR, must be at least 30 mL/min/1.73 m2 before the study starts.
You need to have more than 0.5 grams of protein in your urine in a day.
+11 more
Exclusion Criteria
I have a chronic kidney condition, such as diabetic kidney disease.
I have not taken immunosuppressants like steroids for more than 2 weeks in the last 3 months.
My hemoglobin is below 9 g/dL or I've had a blood transfusion for anemia in the last 3 months.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Run-in
Subjects not on background SGLT2i therapy undergo an 8-week run-in period with an SGLT2i
8 weeks
Treatment Period A
Participants receive 0.75 mg atrasentan once daily for 12 weeks
12 weeks
Visits at Weeks 2, 6, and 12
Washout
A 12-week washout period between treatment periods
12 weeks
Treatment Period B
Participants receive placebo once daily for 24 weeks
24 weeks
Visits at Weeks 2, 6, 12, and 24
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The ASSIST study is testing Atrasentan against a placebo in patients with IgA Nephropathy already taking standard care and an SGLT2 inhibitor. It's a phase 2 trial where participants will switch between the drug and placebo at different times without knowing which one they're taking.
2Treatment groups
Experimental Treatment
Group I: Sequence BAExperimental Treatment2 Interventions
Once daily oral administration of placebo for 12 weeks (Period B) followed by once daily oral administration of 0.75 mg atrasentan for 24 weeks (Period A)
Group II: Sequence ABExperimental Treatment2 Interventions
Once daily oral administration of 0.75 mg atrasentan for 12 weeks (Period A) followed by once daily oral administration of placebo for 24 weeks (Period B)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Tufts Medical CenterBoston, MA
University of North Carolina at Chapel Hill - Nephrology and HypertensionChapel Hill, NC
Fides Clinical ResearchAtlanta, GA
University of PennsylvaniaPhiladelphia, PA
More Trial Locations
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Who Is Running the Clinical Trial?
Chinook Therapeutics, Inc.Lead Sponsor
Novartis PharmaceuticalsLead Sponsor
References
Atrasentan for metastatic hormone refractory prostate cancer. [2014](1) Atrasentan (Xinlay(R)) is an anti-cancer drug from a new class of agents called selective endothelin-A receptor antagonists. The orally administered drug is being studied in a subset of patients with advanced prostate cancer. (2) Phase II and III studies evaluating time to clinical and radiographic progression failed to demonstrate a significant benefit with atrasentan versus placebo. (3) The adverse effects, observed more frequently in those treated with atrasentan than in placebo-treated patients, were peripheral edema, rhinitis, headache, infection, dyspnea, and heart failure. (4) Atrasentan's role in the various stages of advanced prostate cancer, and relative to the chemotherapeutic agent docetaxel, has not been determined.
A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. [2022]The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone-refractory prostate cancer (HRPC).
Atrasentan Abbott. [2018]Atrasentan is a selective endothelin ET(A) receptor antagonist under development by Abbott for the potential treatment of cancer, particularly prostate cancer, for which it is in phase III trials [413197]. In July 2002, phase II trials for renal, ovarian, lung, colorectal, breast and brain cancers were being initiated [457800]. Atrasentan has been granted Fast Track status, allowing for a rolling NDA [414666], [443479]; the company was planning to begin filing for prostate cancer in late 2003. Atrasentan has also been in phase I trials for hypertension [319405], [326268], but development for this indication had been halted by 2001 [407049].
The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy. [2022]Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors, patients with type 2 diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria. We evaluated whether or not atrasentan, a selective endothelin A receptor antagonist, further reduces albuminuria when administered concomitantly with maximum tolerated labeled doses of RAS inhibitors. We enrolled 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) in two identically designed, parallel, multinational, double-blind studies. Participants were randomized to placebo (n=50) or to 0.75 mg/d (n=78) or 1.25 mg/d (n=83) atrasentan for 12 weeks. Compared with placebo, 0.75 mg and 1.25 mg atrasentan reduced urine albumin/creatinine ratios by an average of 35% and 38% (95% confidence intervals of 24 to 45 and 28 to 47, respectively) and reduced albuminuria≥30% in 51% and 55% of participants, respectively. eGFR and office BP measurements did not change, whereas 24-hour systolic and diastolic BP, LDL cholesterol, and triglyceride levels decreased significantly in both treatment groups. Use of atrasentan was associated with a significant increase in weight and a reduction in hemoglobin, but rates of peripheral edema, heart failure, or other side effects did not differ between groups. However, more patients treated with 1.25 mg/d atrasentan discontinued due to adverse events. After stopping atrasentan for 30 days, measured parameters returned to pretreatment levels. In conclusion, atrasentan reduced albuminuria and improved BP and lipid spectrum with manageable fluid overload-related adverse events in patients with type 2 diabetic nephropathy receiving RAS inhibitors.
Addition of atrasentan to renin-angiotensin system blockade reduces albuminuria in diabetic nephropathy. [2022]Although endothelin-receptor antagonists reduce albuminuria in diabetic nephropathy, fluid retention limits their use. Here, we examined the effect of atrasentan, a selective endothelin A receptor (ET(A)R) antagonist, on albuminuria in a randomized, double-blind, placebo-controlled trial of subjects with diabetic nephropathy already receiving stable doses of renin-angiotensin system (RAS) inhibitors. We randomly assigned 89 subjects with eGFR >20 ml/min per 1.73 m(2) and a urinary albumin-to-creatinine ratio (UACR) of 100 to 3000 mg/g to placebo or atrasentan (0.25, 0.75, or 1.75 mg daily) for 8 weeks. Compared with placebo, atrasentan significantly reduced UACR only in the 0.75- and 1.75-mg groups (P=0.001 and P=0.011, respectively). Compared with the 11% reduction in the geometric mean of the UACR from baseline to final observation in the placebo group during the study, the geometric mean of UACR decreased by 21, 42, and 35% in the 0.25-, 0.75-, and 1.75-mg atrasentan groups (P=0.291, P=0.023, and P=0.073, respectively). In the placebo group, 17% of subjects achieved ≥40% reduction in UACR from baseline compared with 30, 50, and 38% in the 0.25-, 0.75-, and 1.75-mg atrasentan groups, respectively (P=0.029 for 0.75 mg versus placebo). Peripheral edema occurred in 9% of subjects receiving placebo and in 14, 18, and 46% of those receiving 0.25, 0.5, and 1.75 mg atrasentan, respectively (P=0.007 for 1.75 mg versus placebo). In summary, atrasentan, at the doses tested, is generally safe and effective in reducing residual albuminuria and may ultimately improve renal outcomes in patients with type 2 diabetic nephropathy.