INAXAPLIN for APOL1-mediated proteinuric kidney disease (AMKD)

Inclusion criteria

• {"criterion_text":"- 1. Subject (or their legally appointed representative) will sign and date informed consent form (ICF) and, when appropriate, an assent form.\n- 2. Willing and able to comply with scheduled visits, treatment plan, study restrictions laboratory tests, contraceptive guidelines, and other study procedures.\n- 3. Subject has an APOL1 genotype of G1/G1, G2/G2, or G1/G2 obtained with a Vertex-designated investigational clinical study assay.\n- 4. For Phase 2, subjects must be between the ages of 18 and 65 years at time of signing first ICF, inclusive. For Phase 3, subjects must be between the ages of 12 and 65 years at time of signing 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, the Phase 3 dose is selected, and a recommendation by the IDMC on the inclusion of pediatric subjects is made. Up to approximately 15% of the total number of subjects planned for enrollment may be >61 to ≤65 years of age at time of signing first ICF, inclusive.\n- 5. A BMI of 18 to 45 kg/m2, inclusive, and a total body weight ≥40 kg.\n- 6. A UPCR of ≥0.7 g/g to <10 g/g in the first morning void based on the average of 3 measurements collected on 3 separate days within a 7-day period, during the Screening Period.\n- 7. Estimated glomerular filtration rate (eGFR) ≥25 to < 75 mL/min/1.73 m2 during the Screening Period, based on the Modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without the race adjustment27 for subjects ≥18 years on Day 1 and the Chronic Kidney Disease in Children Under 25 (CKiD-U25) equation2 for subjects <18 years on Day 1.\n- 8. On a stable, maximum tolerated labeled dose (at least 4 weeks before screening) of an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), but not both concomitantly, unless documented to be intolerant to ACE inhibitor/ARB.\n- 9. Subjects taking sodium glucose co-transporter-2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRAs) or permitted immunosuppressants (prednisone ≤10 mg or steroid equivalent, mycophenolate, tacrolimus, cyclosporine, or azathioprine) must have been on a stable dose for 4 weeks before screening.\n- 10. Subjects must be affiliated with a social security scheme."}

Exclusion criteria

• {"criterion_text":"- 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.\n- 2. Evidence of FSGS with a known cause other than due to APOL1 mutations.\n- 3. History of diabetes mellitus. A diagnosis of prediabetes is permitted.\n- 4. Known underlying cause of kidney disease\n- 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 g/dL • Total bilirubin ≥1.5 × upper limit of normal (ULN) • Aspartate transaminase (AST) or alanine transaminase (ALT) ≥2 × ULN • Hemoglobin <9 g/dL.\n- 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 of cardiac disorders\n- 7. Any clinically significant ECG abnormality (as determined by the investigator) or median QTcF of triplicate standard 12-lead ECGs >450 msec at screening.\n- 8. Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, or positive HIV test\n- 9. Screening blood pressure, based on the average of 3 measurements, of ≥180 mm Hg (systolic) or ≥100 mm Hg (diastolic).\n- 10. Pregnant or nursing female subjects. Females of childbearing potential must have a negative pregnancy test at screening (serum test) and Day 1 (urine test).\n- 11. Known hypersensitivity to investigational medicinal product or to any of its excipients."}

Primary endpoints

• {"endpoint_text":"- Percent change in UPCR evaluated from baseline at Week 48 (assessed at the IA)\n- 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)","definition_or_measurement_approach":"Percent change in UPCR evaluated from baseline at Week 48 (assessed at the interim analysis). eGFR slope measured with ≥48 weeks of eGFR data for interim analysis and at least 2 years of eGFR data for the final analysis."}

Secondary endpoints

• {"endpoint_text":"- Time to composite clinical outcome of a sustained decline of ≥30% from baseline in estimated glomerular filtration rate (eGFR), the onset of ESKD (i.e., maintenance dialysis for ≥28 days, kidney transplantation, or a sustained eGFR of <15 mL/min/1.73 m2), or death. Sustained is defined as confirmation by a second measurement after ≥28 days (assessed at the final analysis).","definition_or_measurement_approach":"Time-to-event composite: sustained ≥30% decline in eGFR (confirmed by second measurement ≥28 days later), onset of ESKD (maintenance dialysis ≥28 days, kidney transplant, or sustained eGFR <15 mL/min/1.73 m2), or death; assessed at final analysis."}
• {"endpoint_text":"- Safety and tolerability based on adverse events (AEs), clinical laboratory values (i.e., hematology, serum chemistry, urinalysis, coagulation studies), standard 12-lead ECGs, and vital signs","definition_or_measurement_approach":"Standard safety assessments including AEs, labs (hematology, chemistry, urinalysis, coagulation), 12-lead ECGs and vital signs."}
• {"endpoint_text":"- Plasma PK parameters of VX-147","definition_or_measurement_approach":"Measurement of plasma pharmacokinetic parameters of VX-147 (PK sampling and standard PK analyses)."}
• {"endpoint_text":"- Acceptability of tablet formulation of VX-147 in pediatric subjects using the convenience domain of the Treatment Satisfaction Questionnaire for Medication (TSQM)","definition_or_measurement_approach":"Assessment of acceptability in pediatric subjects via the convenience domain of the TSQM questionnaire."}

Methods

• Recruitment posters (multiple versions and languages: BE_EN, BE_FR, BE_NL; Web poster layouts for France and Belgium).
• Patient brochures and pediatric patient brochures (documented versions for BE and FR in EN/FR/NL).
• Recruitment video/storyboard materials (Adult Genetic Testing Video Storyboard; Recruitment Video Storyboard).
• Dear Doctor letters (with and without hyperlinks) to clinicians.
• Post-genotyping leaflets and 'Next Steps' cards for adults and pediatric subjects.
• Pediatric visit-by-visit guides and pediatric recruitment posters (multiple numbered poster versions).
• Materials explicitly prepared in multiple languages (English, French, Dutch) and country-specific packs (Belgium and France).

Belgium

Earliest CTIS Part Ii Submission Date

09-10-2024

Latest Decision Or Authorization Date

10-06-2025

Processing Time Days

244

Number Of Sites

2

Number Of Participants

3

France

Earliest CTIS Part Ii Submission Date

09-10-2024

Latest Decision Or Authorization Date

07-10-2025

Processing Time Days

363

Number Of Sites

12

Number Of Participants

30

Primary sponsor

Full Name

Vertex Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States