Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy

Phase 2

Active, not recruiting

• Conditions: IgA Nephropathy; Immunoglobulin A Nephropathy
• Interventions: Drug: Atrasentan; Drug: Placebo

• Registration Number: NCT06841094
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The ASSIST study is a phase 2, double-blind, placebo-controlled crossover study to evaluate the safety and efficacy of atrasentan vs. placebo in subjects with IgA nephropathy (IgAN) while on background standard of care therapy and an SGLT2 inhibitor (SGLT2i).

Detailed Description

Approximately 52 patients with biopsy-proven IgAN who are on a background SGLT2i and a maximally tolerated and stable dose of a renin-angiotensin system inhibitor (RASi) \[such as angiotensin converting enzyme inhibitor (ACEi) or angiotensin-receptor antagonist (ARB)\] as part of standard of care, will be randomized to either sequence AB or sequence BA in which they will receive 0.75 mg atrasentan once daily during one period (period A), complete a 12-week washout period, and then receive matching placebo during the other period (period B) as determined by the randomization schema.

Subjects who are not on background SGLT2i therapy must be willing to undergo a run-in period of 8 weeks with an SGLT2i with a 24-hour total urine protein of \> 0.85 grams/day at screening prior to the run-in period and have 24-hour total urine protein of \> 0.5 grams/day at the end of the run-in period to be eligible for randomization.

Subjects will remain on their maximally tolerated and stable dose of RASi and stable dose of SGLT2i therapies for the duration of the study following randomization.

The primary objective of the study is to evaluate the efficacy of atrasentan vs. placebo while on background therapy with SGLT2i.

Subjects will have safety and efficacy assessments for 1 year (52 weeks).

Study Timeline

• Study Start: 2023-07-20
• Status Verified: 2025-02
• Study First Submitted: 2025-02-20
• Study First Submitted QC: 2025-02-20
• Last Update Submitted: 2025-02-20
• Study First Posted: 2025-02-24
• Last Update Posted: 2025-02-24
• Primary Completion: 2025-10-22
• Study Completion: 2026-08-19

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

• Legal adults (per local and country specifications) ≥ 18 years of age at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures.

• Biopsy-proven IgA nephropathy.

• Receiving a maximally tolerated and stable dose of a RASi for at least 12 weeks prior to screening. Investigator discretion should be used in determining maximally tolerated and optimized dose.

• eGFR of at least 30 mL/min/1.73 m^2 at screening based on the 2021 CKD-EPI equation.

• Willing to agree to highly effective forms of contraception, as specified in the protocol, throughout the study and for up to 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 informed consent and comply with all study requirements.

• Inclusion Criteria for SGLT2i stable subjects

  • Receiving a stable dose of an SGLT2i for at least 8 weeks prior to screening
  • Must have a 24-hour urine protein of >0.5 grams/day.

• Inclusion Criteria for Run-In Subjects

  • Must have a 24-hour total urine protein of >0.85 grams/day at screening
  • Willing to participate in an 8-week run-in period with an SGLT2i (per Investigator choice)

• Additional Inclusion Criteria for Run-in Subjects at the end of Run-In

  • Must have completed the 8-week run-in period on a stable and well tolerated dose of an SGLT2i
  • Must have a 24-hour total urine protein of >0.5 grams/day confirmed at the Run-in Week 8 visit.
  • Must have an eGFR of ≥ 30 mL/min/1.73 m^2 based on the CKD-EPI equation at their Run-in Week 8 visit.

Exclusion Criteria

• Current diagnosis with another chronic kidney disease, including diabetic kidney disease.
• History of kidney transplantation or other organ transplantation.
• Use of systemic immunosuppressant medications, such as steroids, for more than 2 weeks in the past 3 months.
• Blood pressure above 150 mmHg systolic or 95 mmHg diastolic as evaluated by the Investigator.
• Known history of heart failure or prior hospital admissions for conditions relating to fluid overload that in the opinion of the Principal Investigator or Sponsor might confound the results of the study or pose additional risk to the participant by their participation in the study.
• Clinically significant history of liver disease as assessed by the Investigator.
• Hemoglobin below 9 g/dL as measured by the Investigator or prior history of blood transfusion for anemia within the past 3 months.
• Malignancy within the past 5 years. Exceptions to this criteria include nonmelanoma skin cancer and curatively treated cervical carcinoma in situ.
• For women, pregnancy, breast feeding, or intent to become pregnant during the study. and at least 1 month afterward.
• For men, intent to father a child or donate sperm during the study.
• Have received any investigational agent or approved treatment for IgAN (other than a RAS inhibitor) including SGLT2i (except for subjects in the SGLT2i stable stratum) within 1 month (or 5 half-lives of the agent, whichever is longer) prior to Screening. If the investigational agent is a cytotoxic or immunosuppressive agent then this washout period is 6 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence AB	Atrasentan	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)
Sequence AB	Placebo	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)
Sequence BA	Atrasentan	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)
Sequence BA	Placebo	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)

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Proteinuria at Week 12 in Both Treatment Periods 1 and 2	Baseline and 12 weeks or approximately 3 months	The change in urine protein: creatinine ratio (UPCR) from baseline to Week 12

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Proteinuria at Week 24 in Treatment Periods 2	Baseline and 24 weeks or approximately 6 months	The change in UPCR from baseline to Week 24
Number of Subjects With Adverse Events (AEs)	From informed consent until end of study, approximately 60 weeks	Type, incidence, severity, seriousness, and relatedness of AEs will be collected.
Plasma Concentration of Atrasentan	Treatment Period 1: Pre-dose on Weeks 2, 6 and 12; Treatment Period 2: Pre-dose on Weeks 2, 6, 12 and 24	Blood samples will be collected for the measurement of plasma concentrations of atrasentan.

Trial Locations

Locations (30)

Hospital Ribera Polusa; 🇪🇸 Lugo, Spain

Hospital Universitario De Getafe (HUG); 🇪🇸 Madrid, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Virgen Macarena; 🇪🇸 Sevilla, Spain

Hospital Clinico Universitario; 🇪🇸 Valencia, Spain

NUPEC Cardio; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

University of Alabama at Birmingham (UAB) - The Kirklin Clinic (TKC) - Nephrology Clinic; 🇺🇸 Birmingham, Alabama, United States

Fides Clinical Research; 🇺🇸 Atlanta, Georgia, United States

NANI Research; 🇺🇸 Oak Brook, Illinois, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of North Carolina at Chapel Hill - Nephrology and Hypertension; 🇺🇸 Chapel Hill, North Carolina, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

The St. George Hospital; 🇦🇺 Kogarah, New South Wales, Australia

Prince of Wales Hospital; 🇦🇺 Sydney, New South Wales, Australia

Monash Health- Monash Medical Centre; 🇦🇺 Melbourne, Victoria, Australia

Sunshine Hospital; 🇦🇺 St Albans, Victoria, Australia

Santa Casa de Misericordia de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Universidade Federal de Sao Paulo; 🇧🇷 São Paulo, Sao Paulo, Brazil

Hospital das Clinicas da Faculdade de Medicina da USP; 🇧🇷 São Paulo, Sao Paulo, Brazil

Soon Chun Hyang Central Medical Center (SCHMC) - Soon Chun Hyang University Hospital; 🇰🇷 Cheonan, Chungnam-Do, Korea, Republic of

Hallym University Sacred Heart Hospital; 🇰🇷 Anyang, Gyeonggi-do, Korea, Republic of

Dong-A University Medical Center (Dong-A University Hospital); 🇰🇷 Busan, Korea, Republic of

Chung-Ang University College; 🇰🇷 Seoul, Korea, Republic of

Hopsital Sultanah Aminah Johor Bharu (HSAJB) - Bangunan Bakawali Heodialysis Centre; 🇲🇾 Johor Bahru, Johor Darul Takzim, Malaysia

Universiti Kebangsaan Malaysia (UKM) - Medical Centre (Pusat Perubatan) (Hospital Canselor Tuanku Muhriz (HCTM)); 🇲🇾 Cheras, Kuala Lumpur, Malaysia

Hospital Raja Permaisuri Bainun (HRPB); 🇲🇾 Ipoh, Perak, Malaysia

University Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Malaysia

Hospital Torrecardenas; 🇪🇸 Almería, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital del Vall d´Hebron; 🇪🇸 Barcelona, Spain