Phase
Condition
Kidney Disease
Treatment
N/AClinical Study ID
Ages 18-65 All Genders
Study Summary
Eligibility Criteria
Inclusion
<p style="margin-left:0px;"><strong>Inclusion Criteria</strong></p><p style="margin-left:0px;">1. Subject (or their legally appointed representative) will sign and date informed consent form</p><p style="margin-left:0px;">(ICF) and, when appropriate, an assent form.</p><p style="margin-left:0px;">2. Willing and able to comply with scheduled visits, treatment plan, study restrictions</p><p style="margin-left:0px;">(Section 9.5) laboratory tests, contraceptive guidelines, and other study procedures.</p><p style="margin-left:0px;">3. Subject has an APOL1 genotype of G1/G1, G2/G2, or G1/G2 obtained with a</p><p style="margin-left:0px;">Vertex-designated investigational clinical study assay.</p><p style="margin-left:0px;">4. For Phase 2, subjects must be between the ages of 18 and 65 years at time of signing first</p><p style="margin-left:0px;">ICF, inclusive. For Phase 3, subjects must be between the ages of 10 and 65 years at time of</p><p style="margin-left:0px;">signing first ICF, inclusive. Subjects must be <66 years of age at time of randomization.</p><p style="margin-left:0px;">Pediatric subjects may be enrolled only after IDMC review of Phase 2 data is completed, the</p><p style="margin-left:0px;">Phase 3 dose is selected, and a recommendation by the IDMC on the inclusion of pediatric</p><p style="margin-left:0px;">subjects is made. Up to approximately 15% of the total number of subjects planned for</p><p style="margin-left:0px;">enrollment may be >61 to ≤65 years of age at time of signing first ICF, inclusive.</p><p style="margin-left:0px;">5. A BMI of 18 to 45 kg/m2, inclusive, and a total body weight ≥40 kg.</p><p style="margin-left:0px;">6. A UPCR of ≥0.7 g/g to <10 g/g in the first morning void based on the average of</p><p style="margin-left:0px;">3 measurements collected on 3 separate days within a 7-day period, during the Screening</p><p style="margin-left:0px;">Period.</p><p style="margin-left:0px;">7. Estimated glomerular filtration rate (eGFR) ≥25 to < 75 mL/min/1.73 m2 during the</p><p style="margin-left:0px;">Screening Period, based on the Modified Chronic Kidney Disease Epidemiology</p><p style="margin-left:0px;">Protocol VX21-147-301, Version 6.3 (US) Page 42 of 97</p><p style="margin-left:0px;">Vertex Pharmaceuticals Incorporated Confidential Information</p><p style="margin-left:0px;">Collaboration (CKD-EPI) equation without the race adjustment25 for subjects ≥18 years on</p><p style="margin-left:0px;">Day 1 and the Chronic Kidney Disease in Children Under 25 (CKiD-U25) equation2 for</p><p style="margin-left:0px;">subjects <18 years on Day 1.</p><p style="margin-left:0px;">8. On a stable, maximum tolerated labeled dose (at least 4 weeks before screening) of an</p><p style="margin-left:0px;">angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), but</p><p style="margin-left:0px;">not both concomitantly, unless documented to be intolerant to ACE inhibitor/ARB.</p><p style="margin-left:0px;">9. Subjects taking sodium glucose co-transporter-2 (SGLT2) inhibitors, mineralocorticoid</p><p style="margin-left:0px;">receptor antagonists (MRAs) or permitted immunosuppressants (prednisone ≤10 mg or</p><p style="margin-left:0px;">steroid equivalent, mycophenolate, tacrolimus, cyclosporine, or azathioprine) must have been</p><p style="margin-left:0px;">on a stable dose for 4 weeks before screening.</p><p style="margin-left:0px;">
Exclusion
<strong>Exclusion Criteria</strong></p><p style="margin-left:0px;">1. History of any illness or any clinical condition that, in the opinion of the investigator, might</p><p style="margin-left:0px;">confound the results of the study or pose an additional risk in administering study drug(s) to</p><p style="margin-left:0px;">the subject. This includes, but is not limited to, the following:</p><p style="margin-left:0px;">• Solid organ or bone marrow transplantation</p><p style="margin-left:0px;">• Cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical</p><p style="margin-left:0px;">carcinoma in situ (each being disease-free for the last 5 years)</p><p style="margin-left:0px;">• Clinically significant and active bacterial, viral, fungal, or parasitic infection</p><p style="margin-left:0px;">• Clinically significant liver disease</p><p style="margin-left:0px;">• Ongoing alcohol abuse or illicit drug use</p><p style="margin-left:0px;">• Any condition possibly affecting drug absorption (e.g., gastrectomy, gastrointestinal tract</p><p style="margin-left:0px;">surgery except appendectomy and cholecystectomy)</p><p style="margin-left:0px;">• Stroke or myocardial infarction within 6 months before screening</p><p style="margin-left:0px;">2. Evidence of FSGS with a known cause other than due to APOL1 mutations. This includes but</p><p style="margin-left:0px;">is not limited to the following:</p><p style="margin-left:0px;">• FSGS occurring concomitantly to administration of drugs known to induce FSGS,</p><p style="margin-left:0px;">including but not limited to lithium, interferon, and bisphosphonates (e.g., pamidronate),</p><p style="margin-left:0px;">or FSGS occurring in a subject using intravenous illicit drugs at the time of diagnosis.</p><p style="margin-left:0px;">• FSGS occurring in a subject with known sickle cell disease.</p><p style="margin-left:0px;">• Known genetic mutation other than APOL1 G1 or G2 that is associated with FSGS.</p><p style="margin-left:0px;">• Positive serology for human immunodeficiency virus-1 (HIV-1) or human</p><p style="margin-left:0px;">immunodeficiency virus-2 (HIV-2).</p><p style="margin-left:0px;">3. History of diabetes mellitus. A diagnosis of prediabetes is permitted.</p><p style="margin-left:0px;">4. Known underlying cause of kidney disease in the opinion of the investigator including but</p><p style="margin-left:0px;">not limited to biopsy-confirmed or suspected cases of the following: lupus nephritis,</p><p style="margin-left:0px;">myeloma kidney, glomerular basement membrane disease, membranoproliferative</p><p style="margin-left:0px;">glomerulitis, polycystic kidney disease, sickle cell disease, diabetic nephropathy, HIV</p><p style="margin-left:0px;">nephropathy, autoimmune-induced nephropathy, amyloidosis, anti-phospholipase A2</p><p style="margin-left:0px;">Protocol VX21-147-301, Version 6.3 (US) Page 43 of 97</p><p style="margin-left:0px;">Vertex Pharmaceuticals Incorporated Confidential Information</p><p style="margin-left:0px;">receptor-mediated nephropathy, monoclonal gammopathy related kidney disease,</p><p style="margin-left:0px;">complement related glomerulonephritis, thrombotic microangiopathy or hemolytic uremic</p><p style="margin-left:0px;">syndrome, Alport syndrome, immunoglobulin A (IgA) nephropathy, post-streptococcal</p><p style="margin-left:0px;">glomerulonephritis, or acute kidney injury within the past 3 months if eGFR is not at</p><p style="margin-left:0px;">pre-injury baseline.</p><p style="margin-left:0px;">5. Abnormal laboratory values at screening that present a risk to subject safety in the opinion of</p><p style="margin-left:0px;">the investigator, or any of the following abnormal laboratory values at screening:</p><p style="margin-left:0px;">• Serum albumin <1 g/dL</p><p style="margin-left:0px;">• Total bilirubin ≥1.5 × upper limit of normal (ULN)</p><p style="margin-left:0px;">• Aspartate transaminase (AST) or alanine transaminase (ALT) ≥2 × ULN</p><p style="margin-left:0px;">• Hemoglobin <9 g/dL.</p><p style="margin-left:0px;">6. Risk factors for Torsade de Pointes (e.g., familial long QT syndrome, chronic hypokalemia,</p><p style="margin-left:0px;">heart failure) or concomitant medications that prolong the QT/QTc interval or any history of</p><p style="margin-left:0px;">cardiac disorders that, in the opinion of the investigator, might put the subject at risk or may</p><p style="margin-left:0px;">confound the results of the study.</p><p style="margin-left:0px;">7. Any clinically significant ECG abnormality (as determined by the investigator) or median</p><p style="margin-left:0px;">QTcF of triplicate standard 12-lead ECGs >450 msec at screening.</p><p style="margin-left:0px;">8. Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, or positive</p><p style="margin-left:0px;">HIV test during screening.</p><p style="margin-left:0px;">9. Screening blood pressure, based on the average of 3 measurements, of ≥180 mm Hg</p><p style="margin-left:0px;">(systolic) or ≥100 mm Hg (diastolic) for subjects ≥12 years old, and ≥30 mm Hg above the</p><p style="margin-left:0px;">95th percentile based on age, sex and height for subjects 10 to <12 years old.</p><p style="margin-left:0px;">10. Pregnant or nursing female subjects. Females of childbearing potential must have a negative</p><p style="margin-left:0px;">pregnancy test at screening (serum test) and Day 1 (urine test).</p><p style="margin-left:0px;">11. Participation in another interventional clinical study within 28 days or 5 half-lives, whichever</p><p style="margin-left:0px;">is longer, before the first dose of study drug.</p><p style="margin-left:0px;">12. Inability to adhere to the study restrictions defined in Section 9.5, including restrictions</p><p style="margin-left:0px;">before the first dose of study drug for strong CYP3A4 inhibitors or moderate and strong</p><p style="margin-left:0px;">inducers, cyclophosphamide, rituximab, or high dose systemic corticosteroids (>10 mg/day</p><p style="margin-left:0px;">of prednisone or prednisone equivalent).</p><p style="margin-left:0px;">13. Subject, or close relative or a caregiver of the subject, is the investigator or a subinvestigator,</p><p style="margin-left:0px;">research assistant, pharmacist, study coordinator, or other staff directly involved with the</p><p style="margin-left:0px;">conduct of the study at that site. An adult (aged 18 years or older) who is a relative of a study</p><p style="margin-left:0px;">staff member may be enrolled in the study provided the following:</p><p style="margin-left:0px;">• The adult lives independently of and does not reside with the study staff member; and</p><p style="margin-left:0px;">• The adult participates in the study at a site other than the site at which the family member</p><p style="margin-left:0px;">is employed.</p><p style="margin-left:0px;">14. Known hypersensitivity to investigational medicinal product or to any of its excipients.</p>
Study Design
Study Description
Connect with a study center
The Rogosin Institute
New York, New York 10021
United StatesActive - Recruiting
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