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Trial registered on ANZCTR


Registration number
ACTRN12618001511224
Ethics application status
Approved
Date submitted
30/08/2018
Date registered
10/09/2018
Date last updated
19/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of the effect and safety of sparsentan in the treatment of patients with immunoglobulin A 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] 295787 0
021IGAN17001
Universal Trial Number (UTN)
U1111-1218-8831
Trial acronym
IgAN
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Immunoglobulin A Nephropathy 309216 0
Condition category
Condition code
Renal and Urogenital 308089 308089 0 0
Kidney disease
Inflammatory and Immune System 308310 308310 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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 and maintain systolic blood pressure >100 mmHg and diastolic blood pressure >60 mmHg after 2 weeks will increase their dose to 400 mg at Week 3 through Week 110. If patients do not tolerate the increase in dose, they can move back down to the initial dose for the duration of the study. Patient's compliance with the treatment will be assessed. Patients will be asked to return all unused study medication at each visit.
Intervention code [1] 312120 0
Treatment: Drugs
Comparator / control treatment
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 and maintain systolic blood pressure >100 mmHg and diastolic blood pressure >60 mmHg after 2 weeks will increase their dose to 300 mg at Week 3 through Week 110. If patients do not tolerate the increase in dose, they can move back down to the initial dose for the duration of the study. Patient's compliance with the treatment will be assessed. Patients will be asked to return all unused study medication at each visit.
Control group
Active

Outcomes
Primary outcome [1] 307071 0
Change from baseline in urine protein/creatinine ratio (UP/C) at Week 36
Timepoint [1] 307071 0
After the last patient randomized has undergone the Week 36 visit
Secondary outcome [1] 350545 0
Rate of change in estimated glomerular filtration rate (eGFR) over a 52-week period following initial acute effect of randomized therapy.
Timepoint [1] 350545 0
Week 58 post-randomization
Secondary outcome [2] 350546 0
Rate of change in estimated glomerular filtration rate (eGFR) over a 104-week period following initial acute effect of randomized therapy.
Timepoint [2] 350546 0
Week 110 post-randomization
Secondary outcome [3] 350547 0
Number of patients with urinary protein excretion <=0.3 g/day at Week 36.
Timepoint [3] 350547 0
Week 36 post-randomization

Eligibility
Key inclusion criteria
• 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
• Systolic BP <=150 mmHg and diastolic BP <=100 mmHg at screening
• Agree to contraception
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• 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)
• History of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (HbA1c >8%), or nonfasting blood glucose >180 mg/dL at screening
• 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% or hemoglobin value <9 g/dL at Screening
• Potassium >5.5 mEq/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
• For male: planning to father a child during the course of the study
• Participation in a study of another investigational product within 28 days of screening

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)
Enrolled patients will be randomly assigned in a 1:1 ratio to sparsentan or the active control (irbesartan), based on a predefined randomization code (generated by the Sponsor or designee) via the interactive randomization technology (IRT) at the Day 1/Randomization visit.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software (i.e. computerized sequence generation). Randomized patients will be stratified by their screening eGFR value (30 to <60 mL/min/1.73 m2 and >=60 mL/min/1.73 m2) and screening total urine protein (<=1.75 g/day and >1.75 g/day).
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
Safety/efficacy
Statistical methods / analysis
The primary analysis will test the following hypotheses: H0: Change from baseline in proteinuria (UP/C) at Week 36 is equal between sparsentan and irbesartan; H1: Change from baseline in proteinuria (UP/C) at Week 36 is different between sparsentan and irbesartan. Proteinuria (UP/C) data will be analyzed via a mixed model repeated measures analysis, where UP/C will be analyzed on a log scale and the analysis will be stratified by the randomization strata.

The rate of change in eGFR over 52 and 104 weeks, following acute effect of randomized therapy will each be analyzed via a mixed model random coefficients analysis. The analysis will be stratified by the randomization strata, and the estimates will be annualized for ease of presentation and interpretation.

The number of patients achieving urinary protein excretion <=0.3 g/day at Week 36 will be analyzed via a logistic regression, stratified by the randomization strata.

Descriptive statistics will be used to summarize the safety data. Observed data will be listed by patient.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2018
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
280
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 11644 0
Nepean Hospital - Kingswood
Recruitment hospital [2] 11645 0
John Hunter Hospital - New Lambton
Recruitment hospital [3] 11646 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 11647 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [5] 11648 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [6] 11649 0
Simon Roger Gosford Renal Research - Gosford
Recruitment hospital [7] 11650 0
Prince of Wales Hospital - Randwick
Recruitment hospital [8] 11651 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 23691 0
2747 - Kingswood
Recruitment postcode(s) [2] 23692 0
2305 - New Lambton
Recruitment postcode(s) [3] 23693 0
2065 - St Leonards
Recruitment postcode(s) [4] 23694 0
6009 - Nedlands
Recruitment postcode(s) [5] 23695 0
4575 - Birtinya
Recruitment postcode(s) [6] 23696 0
2250 - Gosford
Recruitment postcode(s) [7] 23697 0
2031 - Randwick
Recruitment postcode(s) [8] 23698 0
2139 - Concord
Recruitment outside Australia
Country [1] 20753 0
United States of America
State/province [1] 20753 0
Country [2] 20754 0
United Kingdom
State/province [2] 20754 0
Country [3] 20755 0
Belgium
State/province [3] 20755 0
Country [4] 20756 0
Czech Republic
State/province [4] 20756 0
Country [5] 20757 0
France
State/province [5] 20757 0
Country [6] 20758 0
Germany
State/province [6] 20758 0
Country [7] 20759 0
Italy
State/province [7] 20759 0
Country [8] 20760 0
Lithuania
State/province [8] 20760 0
Country [9] 20761 0
Poland
State/province [9] 20761 0
Country [10] 20762 0
Portugal
State/province [10] 20762 0
Country [11] 20764 0
New Zealand
State/province [11] 20764 0
Country [12] 20765 0
Taiwan, Province Of China
State/province [12] 20765 0
Country [13] 20766 0
Croatia
State/province [13] 20766 0
Country [14] 20767 0
Estonia
State/province [14] 20767 0
Country [15] 20768 0
Hong Kong
State/province [15] 20768 0
Country [16] 20769 0
Spain
State/province [16] 20769 0
Country [17] 20770 0
Korea, Democratic People's Republic Of
State/province [17] 20770 0

Funding & Sponsors
Funding source category [1] 300379 0
Commercial sector/Industry
Name [1] 300379 0
Retrophin, Inc.
Country [1] 300379 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Retrophin, Inc.
Address
3721 Valley Centre Drive, #200
San Diego, CA 92130 USA
Country
United States of America
Secondary sponsor category [1] 299830 0
Commercial sector/Industry
Name [1] 299830 0
Retrophin, Inc.
Address [1] 299830 0
3721 Valley Centre Drive, #200
San Diego, CA 92130 USA
Country [1] 299830 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301189 0
Sydney Local Health District Human Research Ethics Committee - Concord Repatriation General Hospital EC00118
Ethics committee address [1] 301189 0
Concord Repatriation General Hospital (CRGH)
Building 20, Hospital Road
Concord NSW 2139
Ethics committee country [1] 301189 0
Australia
Date submitted for ethics approval [1] 301189 0
02/07/2018
Approval date [1] 301189 0
07/09/2018
Ethics approval number [1] 301189 0
CH62/6/2018-122

Summary
Brief summary
IgAN is a serious, progressive disease in which 20% to 40% of patients progress to end-stage renal disease (ESRD) within 10 to 20 years of diagnosis. As most patients are diagnosed in their 20s or 30s, they face the prospect of dialysis or the need for kidney transplantation in the prime of their lives. The purpose of the study is to analyse the change in the urine protein/creatinine ratio (UP/C), based on a 24-hour urine sample at Week 36, when comparing sparsentan to irbesartan.

Patients enrolled in the PROTECT study (Protocol 021IGAN17001) will be randomly assigned in a 1:1 ratio (like flipping a coin) to sparsentan or the active control (irbesartan) at the Day 1/Randomization visit. Study medication (sparsentan and irbesartan) will be administered as a single oral morning dose.

The hypothesis to be tested relates to the change in proteinuria (protein in the urine) at Week 36 for sparsentan compared to irbesartan.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86158 0
Dr Jonathan Barratt
Address 86158 0
UHL NHS Trust
The John Walls Renal Unit, Leicester General Hospital
Gwendolen Road, Leicester LE5 4PW, UK
Country 86158 0
United Kingdom
Phone 86158 0
+44-116-258-8043
Fax 86158 0
+44-116-258-4764
Email 86158 0
[email protected]
Contact person for public queries
Name 86159 0
Marilyn Van den Broeck
Address 86159 0
3721 Valley Centre Drive, #200
San Diego, CA 92130 USA
Country 86159 0
United States of America
Phone 86159 0
+1-877-659-5518
Fax 86159 0
Email 86159 0
[email protected]
Contact person for scientific queries
Name 86160 0
Marilyn Van den Broeck
Address 86160 0
3721 Valley Centre Drive, #200
San Diego, CA 92130 USA
Country 86160 0
United States of America
Phone 86160 0
+1-877-659-5518
Fax 86160 0
Email 86160 0
[email protected]

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