PF-07817883 for Kidney Failure

Recruiting at 2 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 5 days

16 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to learn about: * how PF-07817883 is processed in the body of adult participants. * the safety of PF-07817883. These participants will have different levels of kidney function loss: * moderate * severe * none or healthy Participants with moderate, severe or no loss of kidney function may be taken into one of 3 groups. This study is seeking for participants who: * are male or female of 18 to 90 years of age. * have different levels of damage to kidney function or for one of the groups, no damage * are willing to follow the requirements of the study including stay at clinic for 5 nights and 6 days. About, 8 participants may be selected in groups 2 and 3. In group 1, around 8 to 12 participants may be selected. If participants agree to take part in the study, it may take up to 4 weeks to complete all the tests to confirm if they are fit to be in the study. If they seem to be fit for the study, participants will be admitted to a clinic research unit (CRU) at least 8 hours before dosing. On Day 1, participants will receive a single amount of study medicine (Day 1). A series of blood samples will be collected before and after giving medicines. Participants will be discharged from the CRU on Day 5. A follow-up phone call (or CRU visit, if needed), will occur 28-35 days after taking the medicine. The whole study will last for a minimum of 5 weeks and a maximum of 10 weeks.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. Please consult with the study coordinators for more details.

What data supports the idea that PF-07817883 for Kidney Failure is an effective drug?

The available research does not provide any data on PF-07817883 for Kidney Failure. Instead, it discusses other treatments for kidney-related conditions, such as mycophenolate mofetil for nephrotic syndrome, valsartan combined with other drugs for IgA nephropathy, and bortezomib for kidney transplant rejection. Without specific data on PF-07817883, we cannot determine its effectiveness for Kidney Failure compared to these alternatives. ^{1 2 3 4 5}

What safety data is available for PF-07817883 (Ibuzatrelvir) in treating kidney failure?

The provided research does not contain safety data for PF-07817883 (Ibuzatrelvir) in treating kidney failure. The studies focus on other drugs like atazanavir and tenofovir, which are associated with renal issues, but do not mention PF-07817883 or Ibuzatrelvir. ^{6 7 8 9 10}

Is the drug PF-07817883 (Ibuzatrelvir) a promising treatment for kidney failure?

The provided research articles do not mention PF-07817883 (Ibuzatrelvir) or its effects on kidney failure. Therefore, based on the available information, we cannot determine if it is a promising treatment for kidney failure. ^{8 9 11 12 13}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults aged 18 to 90 with varying levels of kidney function, including moderate and severe impairment or no damage at all. Participants must have a stable renal function as indicated by eGFR values and meet body weight requirements. They should be willing to stay in the clinic for an extended period.

Inclusion Criteria

My BMI is at least 16 and I weigh more than 99 lbs.

My kidney function is stable, with eGFR values not varying more than 25%.

Exclusion Criteria

I have a condition that might affect how my body absorbs medication.

I have received a kidney transplant.

Positive test result for severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) infection at the time of screening or Day -1

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment

Participants receive a single dose of PF-07817883 and are monitored for pharmacokinetics and safety

5 days

In-patient stay at clinic for 5 nights and 6 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

28-35 days

Follow-up phone call or CRU visit if needed

Treatment Details

Interventions

• PF-07817883

Trial Overview The study tests how PF-07817883, a potential treatment for Coronavirus, is processed in the body across different levels of kidney health. It involves one dose of medication followed by blood sample collection over several days within a controlled clinical setting.

Participant Groups

Group I: Cohort 3 Experimental Treatment 1 Intervention

Moderate renal impairment

Group II: Cohort 2 Experimental Treatment 1 Intervention

Severe renal impairment

Group III: Cohort 1 Experimental Treatment 1 Intervention

No renal impairment

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Mycophenolate mofetil (MMF) combined with prednisone significantly reduced urine protein levels and increased serum albumin in patients with refractory nephrotic syndrome, with all patients having minor lesions achieving clinical remission.

The treatment was generally safe, with manageable side effects; however, one patient had to withdraw due to decreased hemoglobin, while renal function remained stable throughout the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mycophenolate mofetil in the treatment of primary nephrotic syndrome]. Zhao, M., Chen, X., Chen, Y., et al.[2016]

Combining valsartan with clopidogrel and leflunomide significantly reduced proteinuria in patients with progressive IgA nephropathy, with reductions of 62.35% and 69.47% in the respective treatment groups after 24 months.

The combination treatment was associated with minimal adverse reactions and improved renal function compared to valsartan alone, suggesting it could be a safer and more effective option for managing IgA nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy. Cheng, G., Liu, D., Margetts, P., et al.[2018]

Bortezomib shows promise in lowering donor-specific antibody levels and improving graft survival when administered before or shortly after kidney transplantation, based on recent studies.

Its effectiveness as a treatment for antibody-mediated rejection post-transplant is still uncertain, indicating a need for more randomized trials to establish its long-term success and optimal timing for administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib in kidney transplantation. Shah, N., Meouchy, J., Qazi, Y.[2018]

In a study of 38 patients with HIV-associated nephropathy, adding corticosteroids to antiretroviral therapy significantly improved kidney function (measured by eGFR) over 2 years compared to those on antiretroviral therapy alone.

Despite the improvement in kidney function, the group receiving corticosteroids experienced higher mortality, indicating that routine use of corticosteroids cannot be recommended without further research to identify which patients might benefit safely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa. Wearne, N., Swanepoel, CR., Duffield, MS., et al.[2020]

In a study of 311 patients with IgA nephropathy, corticosteroids combined with cyclophosphamide or leflunomide showed significant improvements in kidney function and protein levels compared to corticosteroids alone or with ACEI/ARB.

Complete remission rates were highest in the corticosteroid plus cyclophosphamide (41%) and leflunomide (52.2%) groups, indicating that these combinations may enhance treatment efficacy, although predictors for complete remission included lower proteinuria and less tubular atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the effectiveness of cyclophosphamide, leflunomide, corticosteroids, or conservative management alone in patients with IgA nephropathy: a retrospective observational study. Chen, S., Yin, Q., Ren, S., et al.[2023]

Atazanavir, a new HIV protease inhibitor known for its favorable side effects and once-daily dosing, was associated with acute renal failure in a young man, marking a significant safety concern.

The renal biopsy revealed acute interstitial nephritis, which is the first documented case of this condition linked to atazanavir, highlighting the need for monitoring renal function in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute interstitial nephritis associated with atazanavir, a new protease inhibitor. Brewster, UC., Perazella, MA.[2015]

In a study of 286 adults who switched from TDF-based antiretroviral therapy to ABC/3TC, renal function improved significantly, with serum creatinine levels decreasing and estimated glomerular filtration rate (eGFR) increasing over 12 months.

Viral suppression remained effective throughout the switch, with over 93% of patients maintaining a plasma viral load of less than 50 copies/mL, regardless of whether they were taking atazanavir or another third drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a switch from tenofovir- to abacavir-based antiretroviral therapy, with or without atazanavir, on renal function. Guillemi, SA., Ling, SH., Dahlby, JS., et al.[2018]

In a study of 14,477 adult HIV patients, atazanavir (ATV) was not significantly associated with an increased risk of nephrolithiasis compared to other protease inhibitors (PIs), suggesting its safety in this regard.

When comparing ATV to PI-free regimens, there was a positive association with nephrolithiasis in the commercial insurance database, but not in the Medicaid database, indicating variability that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nephrolithiasis and renal failure among patients exposed to atazanavir, other PIs and PI-free regimens. Nkhoma, E., Kumar, M., Hines, P., et al.[2018]

In a study of 650 HIV-1-infected adults on tenofovir-containing therapy, 55% experienced rapid kidney function decline (RKFD), but only 2% progressed to stage 3 chronic kidney disease (CKD) over a median follow-up of 54 weeks.

Older age and lower baseline kidney function significantly increased the risk of RKFD, with each 10-year increase in age raising the risk by 70%, while women were found to have nearly four times the risk of developing stage 3 CKD compared to men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of stage 3 chronic kidney disease and progression on tenofovir-based regimens. Zachor, H., Machekano, R., Estrella, MM., et al.[2022]

In a study of 741 HIV-infected women, those taking Tenofovir disoproxil fumarate (TDF) with the boosted protease inhibitor lopinavir/ritonavir (LPV/r) experienced significantly more renal events compared to those taking TDF with nevirapine (NVP), with an odds ratio of 3.12.

While the overall incidence of renal events was low (3.2%), higher baseline HIV-1 RNA levels and lower creatinine clearance were identified as risk factors for developing renal insufficiency that required treatment modification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal events among women treated with tenofovir/emtricitabine in combination with either lopinavir/ritonavir or nevirapine. Mwafongo, A., Nkanaunena, K., Zheng, Y., et al.[2022]

In a study of 399 HIV-infected patients, proximal renal tubular dysfunction (PRTD) was found to be associated with cumulative exposure to tenofovir (TDF) and atazanavir, indicating a significant risk factor for kidney issues in these patients.

The analysis revealed that even after discontinuing TDF treatment, the risk of PRTD remained high, suggesting potential long-term effects on kidney function in individuals receiving antiretroviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy. Dauchy, FA., Lawson-Ayayi, S., de La Faille, R., et al.[2015]

In a review of 65 HIV patients at a specialized clinic, tenofovir (TDF) toxicity was the most common reason for referral, but only 13.2% of patients needed to stop the medication immediately, indicating that TDF can often be continued safely with proper monitoring.

The clinic also highlighted that optimizing blood pressure control was a key outcome, suggesting that hypertension is an important but often overlooked factor contributing to renal dysfunction in HIV patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating presentations and outcomes of a joint HIV-renal clinic. Scott, J., Williams, D.[2018]

In a study of 3520 HIV-infected individuals, switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) resulted in improved estimated glomerular filtration rate (eGFR), particularly in those with lower baseline eGFR levels.

The switch to TAF also led to a decrease in urine protein-to-creatinine ratio (UPCR), indicating reduced proteinuria, which suggests better renal health in patients with renal dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Renal Function After Switching From TDF to TAF in HIV-Infected Individuals: A Prospective Cohort Study. Surial, B., Ledergerber, B., Calmy, A., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Mycophenolate mofetil in the treatment of primary nephrotic syndrome]. [2016]

2. Australia pubmed.ncbi.nlm.nih.gov

Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy. [2018]

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

Bortezomib in kidney transplantation. [2018]

4. England pubmed.ncbi.nlm.nih.gov

The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa. [2020]

5. England pubmed.ncbi.nlm.nih.gov

A comparison of the effectiveness of cyclophosphamide, leflunomide, corticosteroids, or conservative management alone in patients with IgA nephropathy: a retrospective observational study. [2023]

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

Acute interstitial nephritis associated with atazanavir, a new protease inhibitor. [2015]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of a switch from tenofovir- to abacavir-based antiretroviral therapy, with or without atazanavir, on renal function. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Nephrolithiasis and renal failure among patients exposed to atazanavir, other PIs and PI-free regimens. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Incidence of stage 3 chronic kidney disease and progression on tenofovir-based regimens. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Renal events among women treated with tenofovir/emtricitabine in combination with either lopinavir/ritonavir or nevirapine. [2022]

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

Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy. [2015]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Investigating presentations and outcomes of a joint HIV-renal clinic. [2018]

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

Changes in Renal Function After Switching From TDF to TAF in HIV-Infected Individuals: A Prospective Cohort Study. [2022]