This randomized, double-blind, placebo-controlled Phase 2/3 adaptive study will first evaluate two doses of VX-147 in subjects with APOL1-mediated proteinuric kidney disease for 12 weeks to select a dose for Phase 3 and subsequently evaluate the efficacy and safety of the single, selected dose in the Phase 3 portion of the study.
The study comprises three periods: screening, treatment, and follow-up. The initial treatment period for Phase 2 is 12 weeks. Subjects enrolled for Phase 2 and Phase 3 who receive the non-selected dose will switch to the Phase 3 dose in a blinded manner after the Phase 3 dose is determined. The study will complete when 187 composite clinical outcome events are accrued among subjects in Phase 2 and Phase 3 who received placebo or the Phase 3 dose and when all enrolled subjects have at least 2 years of eGFR data.

The purpose of this study is to test to see if you have a certain genetic mutation (changes in DNA) so we can learn more about kidney disease. The study involves one blood and saliva test and takes about 30 minutes. The blood test is to see if you have genetic changes in your DNA of a protein called APOL1. People who have this gene mutation may be at risk of losing their kidney function faster than others. The test won't cost you anything. In fact, if you decide to participate, you will be compensated $45. You should know that the test used to determine if you have an APOL1 genetic mutation is not FDA approved, however the FDA has approved this test for research purposes. If you were to participate in this study and take the blood test, and the result indicated you have this mutation, there may be an opportunity in the future to volunteer in an additional research study where you will receive the treatment. This treatment is designed by Vertex, especially for people with kidney disease from APOL1 mutation.