VX-147 for Kidney Disease

(AMPLITUDE Trial)

Recruiting at 276 trial locations

Overseen By Medical Information

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Transplant, Uncontrolled hypertension, Diabetes, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing VX-147, a new drug, in adults and children with a genetic form of kidney disease. The drug aims to reduce the harmful effects of a specific protein in the kidneys.

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.

What makes the drug VX-147 unique for treating kidney disease?

VX-147 (Inaxaplin) is unique because it is specifically designed to target the underlying causes of kidney disease, potentially offering a novel approach compared to existing treatments that often focus on managing symptoms rather than addressing the root cause. ^{1 2 3 4 5}

Eligibility Criteria

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?

Trial Timeline

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

Treatment Details

Interventions

• Placebo (Drug)
• VX-147 (Small Molecule)

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

[Anuria in HIV+ patients treated with indinavir]. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Effective elimination of high-dose methotrexate by repeated hemodiafiltration and high-flux hemodialysis in patients with acute kidney injury. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Coadministration of vindesine with high-dose methotrexate therapy increases acute kidney injury via BCRP, MRP2, and OAT1/OAT3. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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