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Clinical Trials/2024-513227-16-00
2024-513227-16-00
Recruiting
Phase 3

A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Atrasentan in Patients with IgA Nephropathy at Risk of Progressive Loss of Renal Function (The ALIGN Study)

Novartis Pharma AG23 sites in 6 countries42 target enrollmentStarted: August 20, 2024Last updated:
Interventionsatrasentan

Overview

Phase
Phase 3
Status
Recruiting
Enrollment
42
Locations
23
Primary Endpoint
The change in proteinuria (urine protein:creatinine ratio [UPCR] based on 24-hour urine collection) from baseline to Week 36 (non-SGLT2i stratum).

Overview

Brief Summary

To evaluate the effect of atrasentan versus placebo on proteinuria Open Label Extension: to futher characterize the safety of atrasentan

Eligibility Criteria

Ages
18 years to 65+ years (65+ Years, 18-64 Years)
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • Male and female subjects aged 18 and older at the time of signing the ICF prior to initiation of any study specific activities/procedures.
  • Open Label Extension - Subjects from the double-blind portion of study who have completed treatment throguh Week 132 and completed the Week 136 visit. Note: Subjects who were randomized to the non-SGLT2i stratum in the double-blind portion of the study may start SGLT2i during the OL extension
  • Open Label Extension - Subjects entering the OL extension must enroll and have their OLBaseline visit within 14 days of Week 136 (OL Screening visit). Note: If enrollment in the OL extension was not possible due to administrative delays, patients who have completed the EOS visit in the double-blind portion of the study may be able to enroll in the open-label extension if less than 90 days have passed since their EOS visit after approval by Sponsor's Medical Monitor. If enrollment in the OL extension is > 30 days after Week 136, the patient must repeat the Week 136 laboratory assessments to confirm eligibility.
  • Open Label Extension - All fertile men and WOCBP who engage in heterosexual intercourse must be willing to abide with highly effective forms of contraception, as specified in the protocol, throughout the study and for 1 month afterward. In WOCBP, use of contraceptive agents must have been continued after completing the double-blind portion of the study.
  • Biopsy-proven IgAN that, in the opinion of the Investigator, is not due to secondary causes. Biopsy could have occurred at any point in time prior to study. A diagnostic report must be available for review by the Sponsor or designee.
  • Receiving a maximally tolerated and optimized dose of a RAS inhibitor that has been stable for at least 12 weeks prior to screening. Investigator discretion should be used in determining maximally tolerated and optimized dose. Subjects who are intolerant to RAS inhibitors are eligible but will not exceed ~5% of total population randomized (applicable only to non- SGLT2i stratum)
  • Total urine protein ≥1 g/day as measured via 24-hour urine collection at a central laboratory collected at screening.
  • eGFR of at least 30 mL/min/1.73 m2 at screening based on the CKDXML File Identifier: NPqJMh0cM61lInVTZ7wGR8FZHeo= Page 10/23 EPI equation.
  • All fertile men and WOCBP who engage in heterosexual intercourse must be willing to abide with highly effective forms of contraception, as specified in the protocol, throughout the study and for 1 month afterward. In WOCBP, use of hormonal contraceptive agents must have been started at least 1 month prior to Baseline.
  • Willing and able to provide written informed consent and comply with all study visits and study procedures.

Exclusion Criteria

  • Concurrent diagnosis of another cause of chronic kidney disease including diabetic kidney disease or another primary glomerulopathy.
  • Clinical suspicion of rapidly progressive glomerulonephritis (RPGN) based on KDIGO guidelines or clinical suspicion of Henoch-Schonlein Purpura (IgA vasculitis).
  • Clinical diagnosis of nephrotic syndrome.
  • BNP value of > 200 pg/mL at screening.
  • Platelet count <80,000 per μL at screening.
  • History of organ transplantation (subjects with history of corneal transplant are not excluded).
  • Use of systemic immunosuppressant medications including, systemic corticosteroids (e.g. prednisone, prednisolone, nefecon, etc.), mycophenolate, azathioprine, cyclosporine, tacrolimus, etc.; use of herbs such as Tripterygium Wilfordii Hook F, Caulis sinomenii and Sinomenium acutum; for > 2 weeks in the past 3 months. Use of rituximab within the past 6 months.
  • Confirmed blood pressure >150 mmHg systolic or >95 mmHg diastolic based on a mean of 3 measurements obtained at screening.
  • Known history of heart failure or conditions relating to fluid overload such as pulmonary edema, uncontrolled peripheral edema, pleural effusion, or ascites.
  • History of an alcohol or illicit drug-related disorder within the past 3 years.

Arms & Interventions

atrasentan

Experimental

Participants receiving atrasentan

Intervention: atrasentan (Drug)

Outcomes

Primary Outcomes

The change in proteinuria (urine protein:creatinine ratio [UPCR] based on 24-hour urine collection) from baseline to Week 36 (non-SGLT2i stratum).

The change in proteinuria (urine protein:creatinine ratio [UPCR] based on 24-hour urine collection) from baseline to Week 36 (non-SGLT2i stratum).

Secondary Outcomes

  • Change from baseline to final study visit (Week 136, 4 weeks post end of treatment) in eGFR, using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation (non-SGLT2i stratum)
  • Percent of subjects meeting the composite endpoint of experiencing at least one of the following during the study (non-SGLT2i stratum): 1) At least a 30% reduction in eGFR sustained for at least 30 days, 2) eGFR <15 mL/min/1.73m2, sustained for at least 30 days, 3) Chronic dialysis, ≥30 days, 4) Kidney transplantation, 5) All-cause mortality
  • Percent of subjects achieving reduction of proteinuria to < 1 g/day at Week 36 and a 25% decrease in total urine protein from Baseline (non-SGLT2i stratum).
  • Open Label Extension: Change from OL Baseline to OL Week 36 in UPCR based on 24-hour urine collection
  • Open Label Extension: Change from OL Baseline to OL Week 52 in eGFR, using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation

Investigators

Sponsor Class
Pharmaceutical company
Responsible Party
Principal Investigator
Principal Investigator

Katharina Boehm

Scientific

Novartis Pharma AG

Study Sites (23)

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