APOL1-mediated Proteinuric Kidney Disease MedDRA version: 20.0 Level: SOC Classification code 10038359 Term: Renal and urinary disorders System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: VX-147
Product Code: VX-147
Pharmaceutical Form: Tablet
INN or Proposed INN: inaxaplin
Current Sponsor code: VX-147
Other descriptive name: VX-147
Concentration unit: mg milligram(s)
Con
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject (or their legally appointed representative) will sign and date informed consent form (ICF) and, when appropriate, an assent form. 2. Willing and able to comply with scheduled visits, treatment plan, study restrictions laboratory tests, contraceptive guidelines, and other study procedures. 3. Subject has an APOL1 genotype of G1/G1, G2/G2, or G1/G2 obtained with a Vertex designated investigational clinical study assay. 4. For Phase 2, subjects must be between the ages of 18 years at time of signing ICF and 65 years at Screening, inclusive. For Phase 3, subjects must be between the ages of 12 years at time of signing ICF and 65 years at Screening, inclusive. Up to approximately 15% of the total number of subjects planned for enrollment may be >61 to =65 years of age. 5. A BMI of 18.0 to 40.0 kg/m2, inclusive, and a total body weight =40 kg. 6. A UPCR of =0.7 g/g and =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject. This includes, but is not limited to, the following: • Solid organ or bone marrow transplantation • Cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (each being disease-free for the last 5 years) • Clinically significant and active bacterial, viral, fungal, or parasitic infection • Clinically significant liver disease • Ongoing alcohol abuse or illicit drug use • Any condition possibly affecting drug absorption (e.g., gastrectomy, gastrointestinal tract surgery except appendectomy and cholecystectomy) • Stroke or myocardial infarction within 6 months before screening 2. Evidence of FSGS with a known cause other that due to APOL1 mutations. This includes but is not limited to the following: • FSGS occurring concomitantly to administration of drugs known to induce FSGS, including but not limited to lithium, interferon, and bisphosphonates (e.g., pamidronate), or FSGS occurring in a subject using intravenous illicit drugs at the time of diagnosis. • FSGS occurring in a subject with known sickle cell disease. • Known genetic mutation other than APOL1 G1 or G2 that is associated with FSGS. • Positive serology for human immunodeficiency virus-1 (HIV-1) or human immunodeficiency virus-2 (HIV-2). 3. History of diabetes mellitus. 4. Known underlying cause of kidney disease in the opinion of the investigator including but not limited to biopsy-confirmed or suspected cases of the following: lupus nephritis, myeloma kidney, glomerular basement membrane disease, membranoproliferative glomerulitis, polycystic kidney disease, sickle cell disease, diabetic nephropathy, HIV nephropathy, autoimmune-induced nephropathy, amyloidosis, anti phospholipase A2 receptor-mediated nephropathy, monoclonal gammopathy related kidney disease, complement related glomerulonephritis, thrombotic microangiopathy or hemolytic uremic syndrome, Alport syndrome, immunoglobulin A (IgA) nephropathy, post streptococcal glomerulonephritis, or acute kidney injury within the past 3 months if eGFR is not at pre-injury baseline. 5. Abnormal laboratory values at screening that present a risk to subject safety in the opinion of the investigator, or any of the following abnormal laboratory values at screening: • Serum albumin 450 msec at screening. 8. Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, or positive HIV test during screening. 9. Screening blood pressure, based on the average of 3 measurements, of =150 mm Hg (systolic) or =90 mm Hg (diastolic), for subjects =18 years old and =140 mm Hg systolic and =90 mm Hg diastolic for subjects <18 years old. 10. Pregnant or nursing female sub
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Study end;Secondary end point(s): - Time to composite clinical outcome of a sustained decline of =30% from baseline in estimated glomerular filtration rate (eGFR), the onset of end-stage kidney disease (ESKD; i.e., maintenance dialysis for =28 days, kidney transplantation, or a sustained eGFR of <15 mL/min/1.73 m2) or death. (Sustained is defined as confirmation by a second measurement after =28 days) (assessed at the final analysis) - Safety and tolerability based on adverse events (AEs), clinical laboratory values (i.e., hematology, serum chemistry, coagulation studies, urinalysis), standard 12-lead ECGs, and vital signs - Plasma PK parameters of VX-147 | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the efficacy of VX-147 to reduce proteinuria - To evaluate the efficacy of VX 147 on renal function as measured by eGFR slope ;Secondary Objective: - To evaluate the efficacy of VX-147 to decrease the risk of the composite clinical outcome - To evaluate the safety and tolerability of VX-147 - To identify the optimal dose from Phase 2 to carry forward to Phase 3 - To characterize the plasma pharmacokinetics (PK) of VX-147 ;Primary end point(s): - Percent change in UPCR from baseline at Week 48 (assessed at the IA) - eGFR slope (with =48 weeks of eGFR data assessed at the IA and at least 2 years of eGFR data assessed at the final analysis) ;Timepoint(s) of evaluation of this end point: - From baseline to Week 48. - From baseline to at least 2 years. | — |
Countries
Belgium, Brazil, Canada, Colombia, France, Ghana, Martinique, Netherlands, Portugal, Puerto Rico, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed