SPARSENTAN for Proteinuric glomerular diseases|Focal segmental glomerulosclerosis|Minimal change disease|IgA nephropathy|IgA vasculitis|Alport syndrome

Inclusion criteria

• {"criterion_text":"- 1. For All Subjects (All Three Populations) - The subject or parent/legal guardian is willing and able to provide signed informed consent/assent, the subject is willing to provide assent before any screening procedures.\n- 3. For Population 3- Subject weighs ≥40 kg\n- 4. For Population 3- The subject has been on ACEI and/or ARB therapy for at least 12 weeks prior to screening.\n- 2. For All Subjects (All Three Populations) - The subject has an eGFR ≥30 mL/min/1.73 m2 at screening.\n- 3. For All Subjects (All Three Populations) - The subject has a mean seated blood pressure between the 5th and 95th percentile for sex and height.\n- 1. For Population 1 - Male or female ≥1 year at screening to <18 years of age at Day 1.\n- 2. For Population 1 - Has a UP/C ≥1.5 g/g (170 mg/mmol) at screening AND one of the following: • Kidney biopsy-proven FSGS or MCD histological patterns and clinical presentation consistent with primary FSGS or MCD and qualifying proteinuria at screening despite history or ongoing treatment with corticosteroids and/or other immunosuppressive disease-modifying agents • Documentation of a genetic mutation in a podocyte protein associated with FSGS or MCD. Subjects with a documented podocytic mutation do not require kidney biopsy • Kidney biopsy-proven FSGS histological pattern with medical history and clinical presentation consistent with maladaptive cause of the lesion.\n- 1. For Population 2 - Male or female ≥2 years to <18 years of age at Day 1 (Baseline).\n- 2.For Population 2 - Has UP/C ≥0.6 g/g (68 mg/mmol) at screening AND one of the following: • Kidney biopsy-confirmed IgAN, IgAV or AS • Diagnosis of AS by genetic testing (pathogenic X-linked COL4A5 mutation OR autosomal-recessive mutations in both alleles of COL4A3 and/or COL4A4 OR autosomal-dominant COL4A3 and/or COL4A4 and digenic mutations [ie, simultaneous mutations in 2 of the COL4A3, COL4A4, and COL4A5 genes].\n- 1. For Population 3- Male or female ≥8 years at screening and <18 years of age at Day 1 (Baseline).\n- 2. For Population 3- The subject has UP/C ≥1.0 g/g (113 mg/mmol) at screening AND has kidney biopsy-confirmed IgAN"}

Exclusion criteria

• {"criterion_text":"- For All Subjects (All Three Populations) 1. Weighs <7.3 kg at screening\n- Female of childbearing potential who do not agree to use 1 highly reliable method of contraception from 7 days before the first dose of the study medication until 28 days after the last dose of study medication and have a - serum pregnancy test at screening and a - urine pregnancy, with + results confirmed by serum, at every study visit\n- Has participated in a study of another study medication within 28 days before screening or plans to participate in such a study during the course of this study\n- Has FSGS or MCD histological pattern secondary to viral infections, drug toxicities, or malignancies\n- The subject has had prior exposure to sparsentan\n- The subject or parent/legal guardian is unable to adhere to the requirements of the study\n- Has immunoglobulin A (IgA) glomerular deposits not in the context of primary IgAN or IgAV (ie, secondary to another condition\n- The subject has had an acute onset or presentation of glomerular disease or a diagnostic biopsy or a relapse of glomerular disease requiring new or different class of immunosuppressive treatment within 6 months before screening\n- Taking chronic immunosuppressive medications and not on a stable dose for ≥1 month before screening\n- Requires any of the prohibited concomitant medications\n- Has undergone any organ transplantation, with the exception of corneal transplants\n- Has clinically significant congenital vascular disease\n- Has a documented history of congenital or acquired heart failure and/or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema\n- Has hemodynamically significant cardiac valvular disease\n- For Population 3 - The subject is unable to swallow the study medication tablets whole.\n- Has jaundice, hepatitis, or known hepatobiliary disease, or ALT and/or AST >2 times the UL of normal at screening\n- Has a history of malignancy within the past 2 years\n- Has a screening hematocrit <27% (0.27 L/L) or a hemoglobin value <9 g/dL (90 g/L)\n- Has a screening potassium value >5.5 mEq/L (5.5 mmol/L)\n- Has any abnormal clinical laboratory screening values that are considered to be clinically significant\n- Has a history of allergy to any Ang II antagonist or ERA, including sparsentan, or has a hypersensitivity to any of the excipients\n- Female is pregnant, plans to become pregnant during the course of the study, or is breastfeeding"}

Primary endpoints

• {"endpoint_text":"- The incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events (AEs) leading to treatment discontinuation, and adverse events of interest (AEOIs)","definition_or_measurement_approach":"Incidence measured as counts/rates of TEAEs, SAEs, AEs leading to discontinuation, and specified AEOIs observed during treatment."}
• {"endpoint_text":"- Change from baseline in urine protein/creatinine ratio (UP/C) over 108 weeks","definition_or_measurement_approach":"Change from baseline in UP/C measured over a 108-week treatment period."}

Secondary endpoints

• {"endpoint_text":"- Observed plasma PK concentrations at scheduled timepoints and visits","definition_or_measurement_approach":"Measurement of plasma pharmacokinetic concentrations at predefined timepoints and visits."}
• {"endpoint_text":"- Relevant steady-state PK parameters (area under the plasma concentration-time curve during a dosing interval [AUCτ], maximum steady-state plasma drug concentration [Cmax_ss], and minimum steady-state plasma drug concentration [Cmin_ss])","definition_or_measurement_approach":"Calculation of steady-state PK parameters including AUCτ, Cmax_ss and Cmin_ss from plasma concentration-time data."}
• {"endpoint_text":"- Change from baseline in urine albumin/creatinine ratio (UA/C) and eGFR over 108 weeks","definition_or_measurement_approach":"Change from baseline in UA/C and estimated glomerular filtration rate measured over 108 weeks."}
• {"endpoint_text":"- The proportion of subjects achieving complete remission of proteinuria, defined as UP/C <0.3 g/g, over 108 weeks","definition_or_measurement_approach":"Proportion achieving UP/C <0.3 g/g at assessments over 108 weeks."}
• {"endpoint_text":"- The proportion of subjects with focal segmental glomerulosclerosis (FSGS) and/or minimal change disease (MCD) histological patterns achieving partial remission, defined as UP/C ≤1.5 g/g and >40% reduction in UP/C over 108 weeks","definition_or_measurement_approach":"Proportion meeting criteria of UP/C ≤1.5 g/g and >40% reduction from baseline over 108 weeks among subjects with FSGS and/or MCD histology."}
• {"endpoint_text":"- The proportion of subjects who discontinue study medication due to inability to tolerate the smell, taste, aftertaste, volume of administration, or method of administration of the oral suspension (Population 1 and Population 2).","definition_or_measurement_approach":"Proportion of subjects discontinuing due to tolerability issues related to oral suspension sensory characteristics or administration method in Populations 1 and 2."}

Methods

• Country-specific recruitment procedures (documents: K1_*_Recruitment Procedure for Italy, Germany, Sweden, Poland, Spain, Netherlands).
• Social media templates for recruitment (documents: K2_*_Recruitment Material_Social media template in multiple languages) to be used for outreach.
• Study brochures and study guides (K2_*_Recruitment Material_Brochure and _Study Guide) for families/patients.
• Study informational websites (K2_*_Recruitment Material_Study website / Study Informational Website) in country/language-specific versions.
• Study flyers (K2_*_Recruitment Material_Study Flyer) distributed at sites and locally.
• Consent navigator and bilingual materials (K2_*_Recruitment Material_Consent Navigator_Bilingual) to support informed consent/assent discussions.

Italy

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

03-07-2024

Processing Time Days

90

Number Of Sites

5

Number Of Participants

8

Germany

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

26-06-2024

Processing Time Days

83

Number Of Sites

3

Number Of Participants

5

Sweden

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

24-06-2024

Processing Time Days

81

Number Of Sites

2

Number Of Participants

2

Poland

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

15-07-2024

Processing Time Days

102

Number Of Sites

1

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

26-06-2024

Processing Time Days

83

Number Of Sites

4

Number Of Participants

8

Netherlands

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

25-06-2024

Processing Time Days

82

Number Of Sites

2

Number Of Participants

2

Primary sponsor

Full Name

Travere Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

codes:1|12|2|8|9

Name

Veristat LLC

Responsibilities

code:7

Name

Cytel Inc.

Responsibilities

DMC

Name

4G Clinical B.V.

Responsibilities

IXRS

Name

Q2 Solutions LLC

Responsibilities

PK Sample analysis

Name

Scout Clinical

Responsibilities

Patient Reimbursement

Third parties

• {"country":"United States","full_name":"Clinical Technology Transfer Group PLLC","duties_or_roles":"site contracts management","organisation_type":"Non-Pharmaceutical company"}
• {"country":"India","full_name":"Qinecsa Solutions India Private Limited","duties_or_roles":"SAE reporting","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"Home Healthcare","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Quipment","duties_or_roles":"equipment","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"Serology, Endocrinology, ECG Analysis/review","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"codes:1|12|2|8|9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veristat LLC","duties_or_roles":"code:7","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"QP declaration and QP certification of IMP","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"DMC","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"IXRS","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"PK Sample analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}