Effectiveness and Safety of Sparsentan as treatment for Immunoglobulin A Nephropathy (IgAN)

• Register: EUCTR
• Last refreshed on: 18 January 2021
• Main ID: EUCTR2017-004605-41-CZ
• Date of registration: 17/07/2018
• Prospective Registration: Yes
• Primary sponsor: Travere Therapeutics Inc.
• Public title: Effectiveness and Safety of Sparsentan as treatment for Immunoglobulin A Nephropathy (IgAN)
• Scientific title: A Randomized, Multicenter, Double-blind, Parallel-group, Active-control Study of the Efficacy and Safety of Sparsentan for the Treatment of Immunoglobulin A Nephropathy
• Date of first enrolment: 03/10/2018
• Target sample size: 380
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004605-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Croatia, Czech Republic, Czechia, Estonia, France, Germany, Hong Kong, Italy, Korea, Republic of, Lithuania, New Zealand, Poland, Portugal, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Travere Therapeutics Call Center
• Affiliation: Travere Therapeutics Inc.

• Name: Travere Therapeutics Call Center
• Affiliation: Travere Therapeutics Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria for Double-Blind Period:

1. Male or female, aged =18 years.
2. Biopsy-proven IgAN.
3. Urine total protein value =1.0 g/day at screening.
4. eGFR =30 mL/min/1.73 m2 at screening.
5. The patient has been on a stable dose of ACEI and/or ARB therapy for at least 12 weeks prior to screening.
6. At screening, systolic blood pressure =150 mmHg and diastolic blood pressure =100 mmHg.
7. Women of childbearing potential (WOCBP) must agree to the use of two forms of contraception.

Inclusion Criteria for Open-Label Extension Period:
Based on assessments at the Week 110 visit, a patient must meet all of the following criteria to be eligible for the open-label extension period.
1. The patient completed participation in the double-blind period, including the Week 114 visit.
2. The patient is willing and able to provide signed informed consent for participation in the open-label extension period.
3. The patient did not permanently discontinue study medication during the double-blind period.
4. WOCBP, beginning at menarche, must agree to the use of 1 highly reliable (ie, can achieve a failure rate of <1% per year) method of contraception from 7 days prior to the first dose of study medication until 90 days after the last dose of study medication (including open-label sparsentan). One additional barrier method must also be used during sexual activity, such as a diaphragm or diaphragm with spermicide (preferred), or male partner’s use of male condom or male condom with spermicide (preferred), from the Week 114 visit until 90 days after the last dose of study medication.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 340
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
Exclusion Criteria for the Double-Blind Period:

1. IgAN secondary to another condition.
2. Cellular glomerular crescents present in >25% of glomeruli on renal biopsy within 6 months prior to screening.
3. The patient has a chronic kidney disease (CKD) in addition to IgAN.
4. Any organ transplantation, with the exception of corneal transplants.
5. Treatment with any of the prohibited concomitant medications.
6. Treatment with any systemic immunosuppressive medications (including corticosteroids) for >2 weeks within 3 months prior to screening.
7. Documented history of heart failure and/or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema.
8. Clinically significant cerebrovascular disease and/or coronary artery disease.
9. Jaundice, hepatitis, or known hepatobiliary disease (excluding asymptomatic cholelithiasis), or transaminase levels >2 times the upper limit of the normal range at screening.
10. History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years.
11. A screening hematocrit value <27% (0.27 V/V) or hemoglobin value <9 g/dL (90 g/L).
12. A screening potassium value of >5.5 mEq/L (5.5 mmol/L).
13. Female patient is pregnant, breastfeeding or planning to conceive during the study.
14. Participation in a study of another investigational product within 28 days prior to screening.

Exclusion Criteria for the Open-Label Extension Period:
Based on assessments at the Week 110 and Week 114 visits, a patient who meets any of the following criteria will be excluded from the open-label extension period:
1. The patient has progressed to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT).
2. The patient developed any criteria for discontinuation of study medication or discontinuation from the study, respectively, between Week 110 and Week 114.
3. The patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 110 and Week 114.
4. The patient has an eGFR =20 mL/min/1.73 m2 at Week 110.
5. The female patient is pregnant or is breastfeeding.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

Immunoglobulin A Nephropathy (IgAN)
MedDRA version: 20.0 Level: PT Classification code 10021263 Term: IgA nephropathy System Organ Class: 10038359 - Renal and urinary disorders

Intervention(s)

Product Name: Sparsentan tablets/Over-encapsulated Sparsentan tablets
Product Code: RE-021
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sparsentan
CAS Number: 254740-64-2
Current Sponsor code: RE-021
Other descriptive name: SPARSENTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Irbesartan tablets
Product Name: over-encapsulated Irbesartan Tablets
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Irbesartan
CAS Number: 138402-11-6
Other descriptive name: IRBESARTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Irbesartan tablets
Product Name: over-encapsulated Irbesartan Tablets
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Irbesartan
CAS Number: 138402-11-6
Other descriptive name: IRBESARTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Name: Sparsentan
Product Code: RE-021
Pharmaceutical Form: Tablet
INN or Proposed INN: Sparsentan
CAS Number: 254740-64-2
Current Sponsor code: RE-021
Other descriptive name: SPARSENTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: The efficacy objective of the study is to determine the effect of sparsentan on proteinuria and preservation of renal function, as compared to an angiotensin receptor blocker, in patients with immunoglobulin A nephropathy (IgAN).

The safety objective of the study is to assess the safety and tolerability of sparsentan by double-blind monitoring of safety endpoints.

The open-label objective of the study is to assess the long-term efficacy, safety, and tolerability of open-label treatment with sparsentan in patients with IgAN.

Primary end point(s): Efficacy End points:
The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C) at Week 36.

Safety End points:
• Descriptive statistics will be used to summarize the safety data.

Open-Label Extension Period Endpoints:
Endpoints for the open-label extension period include, but are not necessarily limited to:
• The absolute and percent change from Week 114 in eGFR at each visit
• The percent change from Week 114 in UP/C at each visit
• Changes from Week 114 in QoL at each visit
• Changes from Week 114 in body weight, vital signs, physical examinations, peripheral edema, and clinical laboratory parameters
• Changes from Week 114 in lipid profile (total cholesterol and triglycerides, low density lipoprotein C [LDL-C], and high density lipoprotein C [HDL-C])
• The incidence of TEAEs during the open-label extension period

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Primary efficacy endpoints will be evaluated at Week 36 or as defined above. The primary safety endpoint will be evaluated from randomization to Week 114 or as defined above.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to week 114

Secondary end point(s): Rate of change of eGFR

Secondary ID(s)

2017-004605-41-GB

021IGAN17001

Source(s) of Monetary Support

Travere Therapeutics Inc.

Ethics review

Status: Approved
Approval date: 03/10/2018
Contact: