APOL1-mediated proteinuric kidney disease
Conditions
Interventions
Active substance: VX*147
Activity: APOL1 inhibitor
Strength and route of administration: VX-147 15 mg tablets or matching placebo
tablets for oral administration
Sponsors
Vertex Pharmaceuticals
Eligibility
Age
12 Years to 99 Years
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 (Section 9.5) 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 =40 kg. 6. A UPCR of >=0.7 g/g and =25 to =18 years on Day 1 and CKD-EPI40 equation for subjects =180 mm Hg (systolic) or >=100 mm Hg (diastolic).
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 than 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 =1.5 × upper limit of normal (ULN) • Aspartate transaminase (AST) or alanine transaminase (ALT) >=2 × ULN • Hemoglobin 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 measure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • 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) | — |
Secondary
| Measure | Time frame |
|---|---|
| • 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 =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 • To evaluate the acceptability of VX-147 in pediatric subjects • Acceptability of tablet formulation of VX-147 in pediatric subjects using the convenience domain of the Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 | — |
Countries
Netherlands
Outcome results
None listed