Overview
To evaluate the safety and efficacy of sparsentan tablets for the treatment of patients with proteinuria after kidney transplantation with once-daily dosing for 36 weeks.
Description
This is a 46-week, open-label, multicenter, single-group Phase 4 study to determine the safety and efficacy of sparsentan for the treatment of patients post kidney transplantation with IgAN or FSGS with proteinuria (≥ 0.5 g/g).
Eligible participants with a kidney transplant receiving stable standard of care (SOC) therapy, including standard immunosuppressive therapy (IST) to prevent graft rejection, will be enrolled to receive sparsentan treatment for 36 weeks. Participants will remain on standard IST for the duration of the study and will stop RAASi prior to initiating sparsentan treatment. The final dose of a RAASi should be taken on the day before the Day 1 visit.
Participants with a kidney transplant, at least one year prior to screening, with biopsy-proven IgAN will take 200 mg orally once daily (QD) for 2 weeks, then 400 mg QD through Week 36. Participants with a kidney transplant with FSGS histological pattern in the graft will take 400 mg orally QD for 2 weeks, then 800 mg QD through Week 36.
Study visits will be conducted at Day 5 and Weeks 2, 4, 6, 12, 24, and 36 following Day 1. Following the 36 week treatment period, all participants will complete a 4 week off-sparsentan treatment follow-up period (ie, no study drug), during which time treatment will be at the discretion of the investigator. Participants will have a telephone visit at Week 40.
Eligibility
Inclusion Criteria:
- Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
- Male and female aged ≥18 years
- Participants with a kidney transplant with biopsy-proven IgAN or FSGS histological pattern in the graft.
- A period of >12 months since kidney transplantation.
- UPCR ≥0.5 g/g and eGFR (CKD-EPI creatinine-based formula ≥25 mL/min/1.73 m2.
- Participants who can become pregnant, must agree to the use of 1 highly reliable method of contraception from 7 days prior to the first dose of study intervention until 30 days after the last dose of study intervention.
- Systolic BP ≤160 mmHg and ≥100 mmHg, and diastolic BP ≤100 mmHg and ≥60 mmHg at screening.
- For participants on an ACEI and/or ARB, and/or sodium glucose cotransporter-2 (SGLT2) inhibitor, the dosing regimen(s) is stable for ≥6 weeks prior to screening.
Exclusion Criteria:
- Participant has multiorgan transplants (with the exception of pancreas and corneal transplants).
- Immunosuppressive therapy (IST) regimen for kidney transplant or other chronic ISTs including enteric budesonide that is not stable for >6 weeks prior to Day 1. Exceptions include routine changes in the dose of CNIs to meet target level.
- <3 months after antirejection treatment and active rejection.
- Active bacterial, fungal or viral infection and/or active treatment of infection including BK virus (BKV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Hepatitis B and C <3 months prior to and during the screening period.
- Current treatment for surgical complications.
- History of heart failure (New York Heart Association [NYHA] Class II-IV).
- Jaundice, hepatitis, or known hepatobiliary disease.
- Malignancy within the past 2 years with the exception of adequately treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin, with no evidence or recurrence.
- History of alcohol or illicit drug use disorder
- History of serious side effects or allergic response to any angiotensin II antagonist or ERA.
- Participant requires any of the prohibited concomitant medications
- Treatment with sparsentan <12 weeks prior to screening
- Participant has participated in a study of another investigational product <28 days prior to screening or plans to participate in such a study during the course of this study.
- Hematocrit <27%, hemoglobin <90 g/L (9 g/dL), or potassium >5.5 mmol/L (5.5 mEq/L).
- The participant is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
- The participant, in the opinion of the Investigator, is unable to adhere to the requirements of the study, including the ability to swallow the study IMP whole.
- The participant, in the opinion of the Investigator, has a medical condition or abnormal clinically significant laboratory screening value not listed above that may interfere with the evaluation of sparsentan safety or activity.