Phase 2/3 Adaptive Study of VX-147 in Adult and Pediatric Participants With APOL1- Mediated Proteinuric Kidney Disease Mediated Proteinuric Kidney Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of VX-147 in adult and pediatric participants with apolipoprotein L1 (APOL1)-mediated proteinuric kidney disease.

Official Title
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A Phase 2/3 Adaptive, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of VX-147 in Adult and Pediatric Subjects With APOL1-mediated Proteinuric Kidney Disease

Conditions
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Proteinuric Kidney Disease

Intervention / Treatment
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* Drug: VX-147
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: APOL1 genotype of G1/G1, G2/G2, or G1/G2 Proteinuric kidney disease Key Exclusion Criteria: Solid organ or bone marrow transplant Uncontrolled hypertension History of diabetes mellitus Known underlying cause of kidney disease including but not limited to sickle cell disease Other protocol defined Inclusion/Exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2: VX-147<br>Participants will be randomized to receive different dose levels of VX-147. | Drug: VX-147<br>* Tablets for oral administration.<br>|
| Placebo Comparator: Phase 2: Placebo<br>Participants will receive placebo matched to VX-147. | Drug: Placebo<br>* Tablets for oral administration.<br>|
| Experimental: Phase 3: VX-147<br>Participants will receive VX-147 with the dose to be based on the outcome of Phase 2. | Drug: VX-147<br>* Tablets for oral administration.<br>|
| Placebo Comparator: Phase 3: Placebo<br>Participants will receive placebo matched to VX-147. | Drug: Placebo<br>* Tablets for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48 (Assessed at the Week 48 Interim Analysis) |  | From Baseline at Week 48 | 
| Estimated Glomerular Filtration Rate (eGFR) Slope Assessed at the Week 48 Interim Analysis |  | From Baseline Through >= Week 48 | 
| eGFR Slope Assessed at Study Completion |  | From Baseline Through Study Completion (Approximately 2 Years After the Last Participant Enrolls) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Composite Clinical Outcome of a Sustained Decline of >=30 Percent (%) in eGFR, the Onset of end-stage Kidney Disease or Death |  | From Baseline Through Study Completion (Approximately 2 Years After the Last Participant Enrolls) | 
| Safety and Tolerability as Assessed by Number of Participants With Adverse events (AEs) and Serious Adverse Events (SAEs) |  | Day 1 Through Study Completion (Approximately 2 Years After the Last Participant Enrolls) | 
| Maximum Plasma Concentration (Cmax) of VX-147 |  | Day 1 and Week 40 | 
| Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-147 |  | Day 1 and Week 40 | 
| Observed Pre-dose Plasma Concentration (Ctrough) of VX-147 |  | Day 1 up to Week 40 | 
| Acceptability Tablet Formulation of VX-147 in Pediatric Participants using the Convenience Domain of the Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 |  | Day 1 and Week 48 |