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

Phase

2/3

Condition

Kidney Disease

Treatment

N/A

Clinical Study ID

TX400010

VX21-147-301

Ages 18-65
All Genders

Study Summary

"The AMPLITUDE clinical research study is exploring an investigational study drug, called VX-147, for people living with APOL1-mediated kidney disease. This will involve looking at two different amounts (doses) of the investigational study drug to help doctors and researchers decide which dose is safest and works the best. This study will measure if people who get the investigational drug have better outcomes than those who take the placebo.

About 466 people will take part in this study around the world."

Eligibility Criteria

Inclusion

Inclusion Criteria1. 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 aVertex-designated investigational clinical study assay.4. For Phase 2, subjects must be between the ages of 18 and 65 years at time of signing firstICF, inclusive. For Phase 3, subjects must be between the ages of 10 and 65 years at time ofsigning first ICF, inclusive. Subjects must be <66 years of age at time of randomization.Pediatric subjects may be enrolled only after IDMC review of Phase 2 data is completed, thePhase 3 dose is selected, and a recommendation by the IDMC on the inclusion of pediatricsubjects is made. Up to approximately 15% of the total number of subjects planned forenrollment may be >61 to â‰¤65 years of age at time of signing first ICF, inclusive.5. A BMI of 18 to 45 kg/m2, inclusive, and a total body weight â‰¥40 kg.6. A UPCR of â‰¥0.7 g/g to <10 g/g in the first morning void based on the average of3 measurements collected on 3 separate days within a 7-day period, during the ScreeningPeriod.7. Estimated glomerular filtration rate (eGFR) â‰¥25 to < 75 mL/min/1.73 m2 during theScreening Period, based on the Modified Chronic Kidney Disease EpidemiologyProtocol VX21-147-301, Version 6.3 (US) Page 42 of 97Vertex Pharmaceuticals Incorporated Confidential InformationCollaboration (CKD-EPI) equation without the race adjustment25 for subjects â‰¥18 years onDay 1 and the Chronic Kidney Disease in Children Under 25 (CKiD-U25) equation2 forsubjects <18 years on Day 1.8. On a stable, maximum tolerated labeled dose (at least 4 weeks before screening) of anangiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), butnot both concomitantly, unless documented to be intolerant to ACE inhibitor/ARB.9. Subjects taking sodium glucose co-transporter-2 (SGLT2) inhibitors, mineralocorticoidreceptor antagonists (MRAs) or permitted immunosuppressants (prednisone â‰¤10 mg orsteroid equivalent, mycophenolate, tacrolimus, cyclosporine, or azathioprine) must have beenon a stable dose for 4 weeks before screening.

Exclusion

Exclusion Criteria1. History of any illness or any clinical condition that, in the opinion of the investigator, mightconfound the results of the study or pose an additional risk in administering study drug(s) tothe subject. This includes, but is not limited to, the following:â€¢ Solid organ or bone marrow transplantationâ€¢ Cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervicalcarcinoma in situ (each being disease-free for the last 5 years)â€¢ Clinically significant and active bacterial, viral, fungal, or parasitic infectionâ€¢ Clinically significant liver diseaseâ€¢ Ongoing alcohol abuse or illicit drug useâ€¢ Any condition possibly affecting drug absorption (e.g., gastrectomy, gastrointestinal tractsurgery except appendectomy and cholecystectomy)â€¢ Stroke or myocardial infarction within 6 months before screening2. Evidence of FSGS with a known cause other than due to APOL1 mutations. This includes butis not limited to the following:â€¢ 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.â€¢ FSGS occurring in a subject with known sickle cell disease.â€¢ Known genetic mutation other than APOL1 G1 or G2 that is associated with FSGS.â€¢ Positive serology for human immunodeficiency virus-1 (HIV-1) or humanimmunodeficiency virus-2 (HIV-2).3. History of diabetes mellitus. A diagnosis of prediabetes is permitted.4. Known underlying cause of kidney disease in the opinion of the investigator including butnot limited to biopsy-confirmed or suspected cases of the following: lupus nephritis,myeloma kidney, glomerular basement membrane disease, membranoproliferativeglomerulitis, polycystic kidney disease, sickle cell disease, diabetic nephropathy, HIVnephropathy, autoimmune-induced nephropathy, amyloidosis, anti-phospholipase A2Protocol VX21-147-301, Version 6.3 (US) Page 43 of 97Vertex Pharmaceuticals Incorporated Confidential Informationreceptor-mediated nephropathy, monoclonal gammopathy related kidney disease,complement related glomerulonephritis, thrombotic microangiopathy or hemolytic uremicsyndrome, Alport syndrome, immunoglobulin A (IgA) nephropathy, post-streptococcalglomerulonephritis, or acute kidney injury within the past 3 months if eGFR is not atpre-injury baseline.5. Abnormal laboratory values at screening that present a risk to subject safety in the opinion ofthe investigator, or any of the following abnormal laboratory values at screening:â€¢ Serum albumin <1 g/dLâ€¢ Total bilirubin â‰¥1.5 Ã— upper limit of normal (ULN)â€¢ Aspartate transaminase (AST) or alanine transaminase (ALT) â‰¥2 Ã— ULNâ€¢ Hemoglobin <9 g/dL.6. Risk factors for Torsade de Pointes (e.g., familial long QT syndrome, chronic hypokalemia,heart failure) or concomitant medications that prolong the QT/QTc interval or any history ofcardiac disorders that, in the opinion of the investigator, might put the subject at risk or mayconfound the results of the study.7. Any clinically significant ECG abnormality (as determined by the investigator) or medianQTcF of triplicate standard 12-lead ECGs >450 msec at screening.8. Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, or positiveHIV test during screening.9. Screening blood pressure, based on the average of 3 measurements, of â‰¥180 mm Hg(systolic) or â‰¥100 mm Hg (diastolic) for subjects â‰¥12 years old, and â‰¥30 mm Hg above the95th percentile based on age, sex and height for subjects 10 to <12 years old.10. Pregnant or nursing female subjects. Females of childbearing potential must have a negativepregnancy test at screening (serum test) and Day 1 (urine test).11. Participation in another interventional clinical study within 28 days or 5 half-lives, whicheveris longer, before the first dose of study drug.12. Inability to adhere to the study restrictions defined in Section 9.5, including restrictionsbefore the first dose of study drug for strong CYP3A4 inhibitors or moderate and stronginducers, cyclophosphamide, rituximab, or high dose systemic corticosteroids (>10 mg/dayof prednisone or prednisone equivalent).13. Subject, or close relative or a caregiver of the subject, is the investigator or a subinvestigator,research assistant, pharmacist, study coordinator, or other staff directly involved with theconduct of the study at that site. An adult (aged 18 years or older) who is a relative of a studystaff member may be enrolled in the study provided the following:â€¢ The adult lives independently of and does not reside with the study staff member; andâ€¢ The adult participates in the study at a site other than the site at which the family memberis employed.14. Known hypersensitivity to investigational medicinal product or to any of its excipients.

Study Design

April 26, 2023

Study Description

This study is being done to learn more about the safety and effectiveness of the investigational drug VX-147 in participants with APOL1-Mediated Chronic Kidney Disease.People of recent African ancestry are more likely to have certain APOL1 variants and are more at risk for CKD. Currently, treatment for CKD exists only to control some aspects of the disease, such as high blood pressure. However, it is important to also treat the worsening of the kidney function as well as the underlying cause of CKD. VX-147 is being studied to determine if it can slow or stop the worsening of kidney function as well as target the underlying cause of this disease.VX-147 is an investigational drug; â€œinvestigationalâ€ means the drug is not approved by the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA) in the European Union or health authorities in other countries and is still being tested for safety and effectiveness.

For more information, please contact:

Nelson Chen, Senior Clinical Research Coordinator
646-317-0785
nec9039@nyp.org

Connect with a study center

The Rogosin Institute
New York, New York 10021
United States
Active - Recruiting

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