A study to learn if atrasentan is safe and works in people with IgA nephropathy who are taking an SGLT2i

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Digestive System Diseases [C06]

Trial duration

12 Dec 2023 → 29 Oct 2025

Decision date (initial)

2023-10-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-503828-13-00

WHO UTN

U1111-1290-6758

ClinicalTrials.gov

NCT05834738

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of atrasentan vs placebo while on background therapy with SGLT2i

Secondary objectives 1

1. To evaluate the efficacy of atrasentan vs placebo while on background therapy with SGLT2i at 24 weeks of treatment

Conditions and MedDRA coding

Nephrology

Study design 1 period

Regulatory references

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Subjects aged 18 and older at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures.
2. Biopsy-proven IgAN that, in the opinion of the investigator, is not due to secondary causes. a. Biopsy could have occurred at any point in time prior to study. b. A diagnostic report must be available for review by the Sponsor or designee.
3. Receiving a maximally tolerated and stable dose of a renin-angiotensin system inhibitor (RASi) for at least 12 weeks prior to screening. Investigator discretion should be used in determining maximally tolerated and optimized dose.
4. eGFR ≥ 30 mL/min/1.73 m2 at screening based on the CKD-EPI equation (https://www.kidney.org/professionals/kdoqi/gfr_calculator).
5. Willing to abide with 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
6. Willing and able to provide written informed consent and comply with all study visits and study procedures.
7. Inclusion Criteria for SGLT2i Stable Subjects. Receiving treatment with SGLT2i at a stable dose for at least 8 weeks prior to screening.
8. Inclusion Criteria for SGLT2i Stable Subjects. Must have a 24-hour total urine protein of > 0.5 grams/day
9. Inclusion Criteria for Run-In Subjects. Must have a 24-hour total urine protein of >0.85 grams/day at screening.
10. Inclusion Criteria for Run-In Subjects. Willing to participate in an 8-week run-in period with an SGLT2i.
11. 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.
12. Additional Inclusion Criteria for Run-in Subjects at the end of Run-In. Must have a 24-hour total urine protein of > 0.5 grams/day confirmed at the Week -1 visit
13. Additional Inclusion Criteria for Run-in Subjects at the end of Run-In. Must have an eGFR of ≥ 30 mL/min/1.73 m2 based on the CKD-EPI equation at their Week -1 Visit*. * Please keep in mind for subjects that go through the run-in period with SGLT2i, there is the potential for an acute eGFR reduction of about 10%, but can be up to 30% in rare cases (Meraz-Muñoz, 2021; Heerspink, 2021a).
14. Subjects who are unable to fulfill the last 3 criteria during the run-in period will be considered run-in failures.

Exclusion criteria 18

1. Concurrent diagnosis of another cause of chronic kidney disease including diabetic kidney disease or another primary glomerulopathy.
2. Clinical suspicion of rapidly progressive glomerulonephritis (RPGN) based on KDIGO guidelines or clinical suspicion of Henoch-Schonlein Purpura (IgA vasculitis).
3. Clinical diagnosis of nephrotic syndrome.
4. Diagnosis of Type 1 diabetes.
5. Brain natriuretic peptide (BNP) value of > 200 pg/mL at screening.
6. Platelet count <80,000 per µL at screening.
7. History of organ transplantation (subjects with history of corneal transplant are not excluded).
8. Use of systemic immunosuppressant medications including systemic corticosteroids (e.g., prednisone, prednisolone, budesonide, 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.
9. Confirmed blood pressure >150 mmHg systolic or >95 mmHg diastolic based on a blood pressure measurement obtained at screening.
10. Known history of heart failure or prior hospital admissions for conditions relating to fluid overload such as pulmonary edema, uncontrolled peripheral edema, pleural effusion, or ascites.
11. Known history of clinically significant liver disease or transaminase or bilirubin values more than twice the upper limit of normal. Subjects with treated hepatitis C can be considered for inclusion into the study upon consultation with the Sponsor’s Medical Lead (or designee).
12. Hemoglobin below 9 g/dL at screening or prior history of blood transfusion for anemia within 3 months of screening.
13. History of malignancy unless cancer free for at least 5 years or nonmelanoma skin cancer that was completely resected. A subject with curatively treated cervical carcinoma in situ is eligible for this study.
14. Pregnancy, breast feeding, or intent to become pregnant during the study period and at least 1 month afterward for females.
15. Intent to father a child or donate sperm during the study period and at least 1 month afterward for males.
16. Have received any investigational agent or approved treatment for IgAN (other than a RAS inhibitor and SGT2i) 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.
17. Concurrent clinically significant, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the Investigator or Sponsor’s Medical Lead (or designee), might confound the results of the study or pose additional risk to the subject by their participation in the study
18. History of an alcohol or illicit drug-related disorder within the past 1 year.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The change in proteinuria (UPCR from a 24-hour urine collection) from Baseline to Week 12

Secondary endpoints 1

1. In Treatment Period 2, the change in proteinuria (UPCR from a 24 hour urine collection) from Baseline to Week 24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 8

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications