VX-147 for Kidney Disease

(AMPLITUDE Trial)

Recruiting at 435 trial locations

Overseen By Medical Information

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Transplant, Uncontrolled hypertension, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

466 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called VX-147 (also known as Inaxaplin) for individuals with a specific type of kidney disease linked to certain genes. The main goal is to determine if VX-147 is safe and effective in treating this condition, which causes the kidneys to leak protein into the urine. The study consists of two phases: one tests different doses of VX-147, and the other confirms the best dose. Ideal participants have a known genetic marker for this kidney disease and experience protein in their urine. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that VX-147, also known as Inaxaplin, was safe and well-tolerated in earlier studies. Participants who took single doses up to 165 mg and daily doses up to 120 mg for 14 days did not experience major safety issues. This suggests the treatment is unlikely to cause serious side effects at these levels. Although the current trial is in a later stage, which typically involves gathering more safety information, earlier results offer some confidence in its safety for potential participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney disease?

Researchers are excited about VX-147 for kidney disease because it targets a specific genetic mutation associated with the condition, potentially offering a more personalized approach than current treatments. While most existing therapies focus on managing symptoms or slowing disease progression, VX-147 aims to address the underlying cause. This novel mechanism could lead to more effective and long-lasting results, giving hope to patients who have limited options with standard treatments like ACE inhibitors or ARBs.

What evidence suggests that VX-147 might be an effective treatment for kidney disease?

Research has shown that VX-147, also known as inaxaplin, may help treat kidney disease that causes high protein levels in urine. In studies, this treatment significantly reduced protein levels in urine, an important indicator of kidney disease. Early research suggests that VX-147 works by blocking the APOL1 protein, which is linked to kidney damage. Tests on mice showed a decrease in protein levels in their urine, indicating possible benefits for humans. This trial will compare VX-147 to a placebo to evaluate its effectiveness in slowing kidney disease related to APOL1. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults and kids with a genetic form of kidney disease linked to APOL1 genes. Participants should have protein in their urine, indicating kidney issues, but can't have diabetes, other known causes of kidney disease like sickle cell, uncontrolled high blood pressure, or a history of organ or bone marrow transplants.

Inclusion Criteria

Have you been told to have levels of protein in your urine (this is referred as proteinuria)?

Have you been diagnosed with chronic kidney disease (CKD) or focal segmental glomerulosclerosis (FSGS) syndrome?

Has a doctor told you that you have kidney problem?

Exclusion Criteria

Do you have a history of diabetes?

Are you currently undergoing dialysis treatment?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2 Treatment

Participants receive different dose levels of VX-147 or placebo

8-12 weeks

Phase 3 Treatment

Participants receive VX-147 or placebo based on Phase 2 outcomes

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• VX-147

Trial Overview The study is testing VX-147's effectiveness and safety compared to a placebo (a treatment with no active drug) in treating APOL1-mediated proteinuric kidney disease. It will also look at how the body processes the drug.

How Is the Trial Designed?

Group I: Phase 3: VX-147 Experimental Treatment 1 Intervention

Participants will receive VX-147 with the dose to be based on the outcome of Phase 2.

Group II: Phase 2: VX-147 Experimental Treatment 1 Intervention

Participants will be randomized to receive different dose levels of VX-147.

Group III: Phase 2: Placebo Placebo Group 1 Intervention

Participants will receive placebo matched to VX-147.

Group IV: Phase 3: Placebo Placebo Group 1 Intervention

Participants will receive placebo matched to VX-147.

Who Is Running the Clinical Trial?

Vertex Pharmaceuticals Incorporated

Lead Sponsor

Trials

267

Recruited

36,100+

Dr. David Altshuler

Vertex Pharmaceuticals Incorporated

Chief Medical Officer since 2020

MD, PhD

Dr. Reshma Kewalramani

Vertex Pharmaceuticals Incorporated

Chief Executive Officer since 2020

MD, trained in internal medicine and nephrology

Published Research Related to This Trial

Indinavir, a medication used in HIV+ patients, can lead to severe acute renal failure due to its tendency to crystallize in urine, particularly influenced by dosage and urinary pH.

In the two reported cases, renal failure was resolved by stopping indinavir, providing fluids, and acidifying urine, highlighting the importance of monitoring kidney function in patients on this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anuria in HIV+ patients treated with indinavir]. Rebassa Llull, MJ., Conte Visús, A., Grases Freixedas, F., et al.[2013]

In a study involving 4786 participants with cardiovascular disease and diabetes or metabolic syndrome, low-dose methotrexate (LD-MTX) was found to cause less decline in kidney function compared to a placebo, indicating its potential safety for patients with normal kidney function or mild-to-moderate chronic kidney disease (CKD).

The incidence of kidney adverse events was lower in the LD-MTX group (2.97 per 100 person-years) compared to the placebo group (3.99 per 100 person-years), suggesting that LD-MTX may be a safer option for managing inflammation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial. Sparks, JA., Vanni, KMM., Sparks, MA., et al.[2023]

Chronic kidney disease (CKD) affects 25-30% of type 2 diabetic patients, but many oral antidiabetic medications are not safe or effective for these patients due to renal impairment, necessitating careful management.

Newer antidiabetic agents, particularly dipeptidyl peptidase-4 inhibitors, are generally better tolerated in CKD, although dose adjustments are needed for most except linagliptin, while the safety and efficacy of SGLT2 inhibitors in CKD are still under investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of oral glucose-lowering agents in patients with renal impairment]. Scheen, AJ.[2012]

In three cases of acute kidney injury (AKI) following high-dose methotrexate (HD-MTX) treatment for diffuse large B-cell lymphoma, daily high-flux hemodialysis (HF-HD) or online hemodiafiltration (HDF) effectively enhanced methotrexate elimination when glucarpidase was unavailable.

All patients experienced normalization of renal function within 3-6 weeks, with only one case of severe pancytopenia, demonstrating that repeated dialysis sessions can safely manage methotrexate toxicity in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective elimination of high-dose methotrexate by repeated hemodiafiltration and high-flux hemodialysis in patients with acute kidney injury. Sakran, R., Milo, G., Jabareen, A., et al.[2022]

Coadministration of vindesine (VDS) significantly increases the risk of acute kidney injury (AKI) in patients receiving high-dose methotrexate (HD-MTX), with an odds ratio of 2.62 based on a study of 178 patients across 211 treatment cycles.

The mechanism behind this increased risk is linked to VDS inhibiting key transporters (BCRP, MRP2, and OAT1/OAT3), leading to higher serum concentrations of methotrexate and delayed elimination, which are closely associated with the occurrence of AKI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coadministration of vindesine with high-dose methotrexate therapy increases acute kidney injury via BCRP, MRP2, and OAT1/OAT3. Huang, C., Xia, F., Xue, L., et al.[2022]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2202396

Inaxaplin for Proteinuric Kidney Disease in Persons with ... The primary efficacy outcome was the percent change from the baseline urinary protein-to-creatinine ratio at week 13. Secondary outcomes ...

2. investors.vrtx.com investors.vrtx.com/news-releases/news-release-details/vertex-advances-inaxaplin-vx-147-phase-3-portion-adaptive-phase

Vertex Advances Inaxaplin (VX-147) into Phase 3 Portion ... The clinical trial is designed to assess the impact of inaxaplin on kidney function and proteinuria for people living with proteinuric kidney ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05312879

NCT05312879 | Phase 2/3 Adaptive Study of VX-147 in ... The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of VX-147 in adult and pediatric participants

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36920755/

Inaxaplin for Proteinuric Kidney Disease in Persons with ... Results: In preclinical studies, inaxaplin selectively inhibited APOL1 channel function in vitro and reduced proteinuria in the mouse model. ...

5. ir.zailaboratory.com ir.zailaboratory.com/news-releases/news-release-details/vertex-announces-key-advancements-across-kidney-portfolio

Vertex Announces Key Advancements Across Kidney ... Up to 72% of adult IgAN patients progress to end-stage renal disease within 20 years of diagnosis. There are no approved therapies that ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11006409/

Safety and Tolerability of the APOL1 Inhibitor, Inaxaplin ... Inaxaplin is safe and well tolerated at single doses up to 165 mg and multiple doses up to 120 mg daily for 14 days.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06794996

Study Details | NCT06794996 | Inaxaplin in Participants ... The purpose of the study is to evaluate the efficacy, safety, and tolerability of Inaxaplin (IXP) in participants with proteinuric APOL1- mediated kidney ...