Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03762850




Registration number
NCT03762850
Ethics application status
Date submitted
27/11/2018
Date registered
4/12/2018
Date last updated
3/07/2024

Titles & IDs
Public title
A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy
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
Secondary ID [1] 0 0
2017-004605-41
Secondary ID [2] 0 0
021IGAN17001
Universal Trial Number (UTN)
Trial acronym
PROTECT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immunoglobulin A Nephropathy 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - sparsentan
Treatment: Drugs - irbesartan
Treatment: Drugs - Dapagliflozin

Experimental: sparsentan - Double-blind: Sparsentan will be administered daily as a 200-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 200 mg after 2 weeks will increase their dose to 400- mg and continue treatment to Week 110.

Active comparator: irbesartan - Double-blind: Irbesartan will be administered daily as a 150-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 150 mg after 2 weeks will increase their dose to 300 mg and continue treatment to Week 110.

Experimental: dapagliflozin + sparsentan (Sub study) - OLE Sub study: Dapagliflozin will be administered daily as a 5-mg oral tablet, in addition to 400-mg of Sparsentan, for a period of 12 weeks.

Experimental: sparsentan (Sub Study) - OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.


Treatment: Drugs: sparsentan
Target dose of 400 mg daily

Treatment: Drugs: irbesartan
Target dose of 300 mg daily

Treatment: Drugs: Dapagliflozin
Target dose of 10 mg daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in the Urine Protein/Creatinine (UP/C) at Week 36
Timepoint [1] 0 0
Baseline (Day 1) and at Week 36
Secondary outcome [1] 0 0
Total Slope of Estimated Glomerular Filtration Rate (eGFR) Over a 110-week Period
Timepoint [1] 0 0
From Day 1 to Week 110
Secondary outcome [2] 0 0
Annualized Slope of eGFR Following the Initial Acute Effect of Randomized Treatment (Chronic Slope)
Timepoint [2] 0 0
From Week 6 to Week 110 post randomization

Eligibility
Key inclusion criteria
Key Inclusion Criteria for the Double-Blind Period:

* Age 18 years or older at screening
* Biopsy-proven primary IgAN
* Proteinuria of =1 g/day at screening
* eGFR =30 mL/min/1.73 m2 at screening
* Currently on stable dose of ACEI and/or ARB therapy, for at least 12 weeks prior to screening (maximum tolerated dose and at least one-half of the maximum labeled dose)
* Systolic BP =150 mmHg and diastolic BP =100 mmHg at screening
* Willing to undergo change in ACEI and/or ARB and anti-hypertensive medications
* Agree to contraception

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for the Double-Blind Period:

* IgAN secondary to another condition
* Presence of cellular glomerular crescents in >25% of glomeruli on renal biopsy (if biopsy available within 6 months of screening)
* Chronic kidney disease (CKD) in addition to IgAN
* History of organ transplantation, with exception of corneal transplants
* Require any prohibited medications
* Treatment of systemic immunosuppressive medications (including corticosteroids) for >2 weeks within 3 months of screening
* History of heart failure or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema
* Clinically significant cerebrovascular disease or coronary artery disease within 6 months of screening
* Jaundice, hepatitis, or known hepatobiliary disease or elevations of transaminases (ALT/AST) >2 times upper limit of normal at screening
* History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years
* Hematocrit value <27% (0.27 V/V) or hemoglobin value <9 g/dL (90 g/L) at Screening
* Potassium >5.5 mEq/L (5.5 mmol/L) at Screening
* History of alcohol of illicit drug use disorder
* History of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist, including sparsentan or irbesartan, or has a hypersensitivity to any of the excipients in the study medications
* For female: Pregnancy, or planning to become pregnant during the course of the study, or breastfeeding
* Participation in a study of another investigational product within 28 days of screening

Key Inclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 visit:

* Completed participation in the double-blind period, including the Week 114 visit
* Did not permanently discontinue study medication during the double-blind period
* Agree to contraception

Key Exclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 and Week 114 visits:

* Progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT)
* Development of any criteria for discontinuation of study medication or discontinuation from the study, between Week 110 and Week 114
* Patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 110 and Week 114
* eGFR =20 mL/min/1.73 m2 at Week 110
* Female patient is pregnant or breastfeeding

Key Inclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:

* Participating in the open-label extension and is willing and able to provide signed informed consent for participation in the open-label extension period Sub study
* A urine protein excretion value of =0.3 g/day.
* An eGFR of =25 mL/min/1.73m2
* On a stable dose of sparsentan for =8 weeks in the open-label extension period that is the maximum tolerated dose.

Key Exclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:

* Progressed to ESRD requiring RRT
* Initiated or changed dose of a systemic immunosuppressive medication (including systemic steroids) within 12 weeks
* Taking an SGLT2 inhibitor within 12 weeks

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/12/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
Accrual to date
Final
406
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Travere Investigational Site - Concord
Recruitment hospital [2] 0 0
Travere Investigational Site - Gosford
Recruitment hospital [3] 0 0
Travere Investigational Site - Kingswood
Recruitment hospital [4] 0 0
Travere Investigational Site - New Lambton Heights
Recruitment hospital [5] 0 0
Travere Investigational Site - Randwick
Recruitment hospital [6] 0 0
Travere Investigational Site - St Leonards
Recruitment hospital [7] 0 0
Travere Investigational Site - Birtinya
Recruitment hospital [8] 0 0
Travere Investigational Site - Adelaide
Recruitment hospital [9] 0 0
Travere Investigational Site - Reservoir
Recruitment hospital [10] 0 0
Travere Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2250 - Gosford
Recruitment postcode(s) [3] 0 0
2747 - Kingswood
Recruitment postcode(s) [4] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [5] 0 0
2031 - Randwick
Recruitment postcode(s) [6] 0 0
2065 - St Leonards
Recruitment postcode(s) [7] 0 0
4575 - Birtinya
Recruitment postcode(s) [8] 0 0
5000 - Adelaide
Recruitment postcode(s) [9] 0 0
3073 - Reservoir
Recruitment postcode(s) [10] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
United States of America
State/province [21] 0 0
Wisconsin
Country [22] 0 0
Belgium
State/province [22] 0 0
Bonheiden
Country [23] 0 0
Belgium
State/province [23] 0 0
Brugge
Country [24] 0 0
Belgium
State/province [24] 0 0
Gent
Country [25] 0 0
Belgium
State/province [25] 0 0
Kortrijk
Country [26] 0 0
Belgium
State/province [26] 0 0
Liège
Country [27] 0 0
Belgium
State/province [27] 0 0
Roeselare
Country [28] 0 0
Croatia
State/province [28] 0 0
Osijek
Country [29] 0 0
Croatia
State/province [29] 0 0
Zagreb
Country [30] 0 0
Czechia
State/province [30] 0 0
Praha 10
Country [31] 0 0
Czechia
State/province [31] 0 0
Praha 2
Country [32] 0 0
Estonia
State/province [32] 0 0
Tallinn
Country [33] 0 0
Estonia
State/province [33] 0 0
Tartu
Country [34] 0 0
France
State/province [34] 0 0
Bouches-du-Rhone
Country [35] 0 0
France
State/province [35] 0 0
Herault
Country [36] 0 0
France
State/province [36] 0 0
Isere
Country [37] 0 0
France
State/province [37] 0 0
Loire
Country [38] 0 0
France
State/province [38] 0 0
Paris
Country [39] 0 0
France
State/province [39] 0 0
Puy De Dome
Country [40] 0 0
France
State/province [40] 0 0
Créteil
Country [41] 0 0
Germany
State/province [41] 0 0
Baden Wuerttemberg
Country [42] 0 0
Germany
State/province [42] 0 0
Lower Saxony
Country [43] 0 0
Germany
State/province [43] 0 0
Nordrhein Westfalen
Country [44] 0 0
Germany
State/province [44] 0 0
North Rhine Westphalia
Country [45] 0 0
Germany
State/province [45] 0 0
Rheinland Palatinate
Country [46] 0 0
Germany
State/province [46] 0 0
Schleswig Holstein
Country [47] 0 0
Germany
State/province [47] 0 0
Schleswig-Holstein
Country [48] 0 0
Germany
State/province [48] 0 0
Thueringen
Country [49] 0 0
Germany
State/province [49] 0 0
Berlin
Country [50] 0 0
Hong Kong
State/province [50] 0 0
Kowloon
Country [51] 0 0
Hong Kong
State/province [51] 0 0
New Territories
Country [52] 0 0
Hong Kong
State/province [52] 0 0
Hong Kong
Country [53] 0 0
Italy
State/province [53] 0 0
Bergamo
Country [54] 0 0
Italy
State/province [54] 0 0
Lombardia
Country [55] 0 0
Italy
State/province [55] 0 0
Bari
Country [56] 0 0
Italy
State/province [56] 0 0
Catania
Country [57] 0 0
Italy
State/province [57] 0 0
Catanzaro
Country [58] 0 0
Italy
State/province [58] 0 0
Lecco
Country [59] 0 0
Italy
State/province [59] 0 0
Modena
Country [60] 0 0
Italy
State/province [60] 0 0
Pavia
Country [61] 0 0
Italy
State/province [61] 0 0
Roma
Country [62] 0 0
Italy
State/province [62] 0 0
Torino
Country [63] 0 0
Korea, Republic of
State/province [63] 0 0
Gyeonggi-do
Country [64] 0 0
Korea, Republic of
State/province [64] 0 0
Anyang-Si
Country [65] 0 0
Korea, Republic of
State/province [65] 0 0
Busan
Country [66] 0 0
Korea, Republic of
State/province [66] 0 0
Incheon
Country [67] 0 0
Korea, Republic of
State/province [67] 0 0
Seoul
Country [68] 0 0
Lithuania
State/province [68] 0 0
Kaunas
Country [69] 0 0
Lithuania
State/province [69] 0 0
Vilnius
Country [70] 0 0
New Zealand
State/province [70] 0 0
Auckland
Country [71] 0 0
New Zealand
State/province [71] 0 0
Hamilton
Country [72] 0 0
New Zealand
State/province [72] 0 0
Hastings
Country [73] 0 0
New Zealand
State/province [73] 0 0
New Plymouth
Country [74] 0 0
Poland
State/province [74] 0 0
Kraków
Country [75] 0 0
Poland
State/province [75] 0 0
Olsztyn
Country [76] 0 0
Poland
State/province [76] 0 0
Warszawa
Country [77] 0 0
Poland
State/province [77] 0 0
Wroclaw
Country [78] 0 0
Poland
State/province [78] 0 0
Lódz
Country [79] 0 0
Portugal
State/province [79] 0 0
Coimbra
Country [80] 0 0
Portugal
State/province [80] 0 0
Lisboa
Country [81] 0 0
Portugal
State/province [81] 0 0
Loures
Country [82] 0 0
Portugal
State/province [82] 0 0
Setúbal
Country [83] 0 0
Portugal
State/province [83] 0 0
Vila Nova De Gaia
Country [84] 0 0
Spain
State/province [84] 0 0
Baleares
Country [85] 0 0
Spain
State/province [85] 0 0
Valencia
Country [86] 0 0
Spain
State/province [86] 0 0
Barcelona
Country [87] 0 0
Spain
State/province [87] 0 0
Madrid
Country [88] 0 0
Spain
State/province [88] 0 0
Sevilla
Country [89] 0 0
Spain
State/province [89] 0 0
Zaragoza
Country [90] 0 0
Taiwan
State/province [90] 0 0
Hualien City
Country [91] 0 0
Taiwan
State/province [91] 0 0
Kaohsiung
Country [92] 0 0
Taiwan
State/province [92] 0 0
New Taipei City
Country [93] 0 0
Taiwan
State/province [93] 0 0
Taichung
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Berkshire
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Cambridgeshire
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Cleveland
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Derbyshire
Country [98] 0 0
United Kingdom
State/province [98] 0 0
East Sussex
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Greater London
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Greater Manchester
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Lancashire
Country [102] 0 0
United Kingdom
State/province [102] 0 0
Leicestershire
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Scotland
Country [104] 0 0
United Kingdom
State/province [104] 0 0
Staffordshire
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Strathclyde
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Surrey
Country [107] 0 0
United Kingdom
State/province [107] 0 0
West Glamorgan
Country [108] 0 0
United Kingdom
State/province [108] 0 0
West Midlands
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Liverpool
Country [110] 0 0
United Kingdom
State/province [110] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Travere Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To determine the long-term (approximately 2 years) nephroprotective potential of treatment with sparsentan as compared to an angiotensin receptor blocker in patients with immunoglobulin A nephropathy (IgAN).
Trial website
https://clinicaltrials.gov/study/NCT03762850
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Priscila Preciado, MD
Address 0 0
Travere Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03762850