APOL1 Genotyping for Kidney Disease

Overseen By Ruth A Scott, BSc (Hons)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Almac Diagnostic Services LLC

Disqualifiers: Incomplete consent, Specimen issues, others

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

Compensation: Varies

Number of Visits: 1

1000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new method for identifying specific gene types linked to a form of kidney disease. It will help find people with certain high-risk genes, making them eligible for further testing of a new treatment. The treatment under study is a synthetic antisense oligonucleotide, a type of medicine designed to target and block harmful genetic activity. Participants should have a diagnosis related to APOL1-mediated kidney disease and be identified by their doctor as suitable candidates.

As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research that could lead to new treatment options for kidney disease.

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 prior data suggests that the APOL1 Genotyping Clinical Trial Assay is safe?

Research has shown that scientists are investigating synthetic molecules called antisense oligonucleotides (ASOs) to treat a type of kidney disease linked to the APOL1 gene. In mouse studies, a specific ASO named IONIS-APOL1Rx reduced kidney problems.

ASOs have been tested in various studies and are generally well-tolerated, with most people not experiencing serious side effects. However, like any treatment, some unwanted effects can occur. Researchers are still collecting specific safety information for this ASO in humans, as it remains part of ongoing research.

Overall, the use of ASOs in clinical trials is increasing, indicating growing confidence in their safety. Still, monitoring for any side effects remains important as more people participate in these trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for APOL1-mediated kidney disease, which often focus on managing symptoms and slowing disease progression, the synthetic antisense oligonucleotide (ASO) treatment targets the underlying genetic cause. This ASO works by specifically binding to the RNA of the APOL1 gene, reducing the production of the harmful protein variants associated with high-risk genotypes. Researchers are excited because this approach could potentially offer a more precise and effective way to treat the disease at its genetic root, possibly leading to better outcomes for patients with these high-risk genotypes.

What evidence suggests that the APOL1 Genotyping CTA is effective for identifying candidates for APOL1-mediated kidney disease treatment?

Research has shown that treatments called antisense oligonucleotides (ASOs) can help with APOL1-mediated kidney disease (AMKD). These ASOs lower the activity of the APOL1 gene, which is linked to kidney damage. For example, in studies, the ASO named IONIS-APOL1Rx reduced APOL1 activity and protected mice from kidney damage. Another study found that ASOs improved kidney function in mice with existing kidney disease. This trial involves APOL1 genotyping to identify candidates for a Phase 2b clinical trial investigating the safety and efficacy of a synthetic ASO for treating AMKD. These results suggest that ASOs might be a promising way to manage AMKD by addressing its root cause. ^{1 5 6 7 8}

Who Is on the Research Team?

Richard Kennedy, MD PhD FRCP

Principal Investigator

Almac Diagnostic Services Ltd

Are You a Good Fit for This Trial?

This trial is for individuals who may have a genetic risk for kidney disease. They will be tested to see if they carry certain high-risk genes (APOL1 G1 and G2) that could make them eligible for another study on a new treatment.

Inclusion Criteria

The study participant's specimen must be distributed to the device test site accompanied by a complete Test Request Form signed by the appropriate clinical trial site personnel

Study participants must be identified as a potential candidate for the pharmaceutical company-sponsored clinical trial by their physician based on the clinical trial inclusion criteria

All participant specimens must meet predetermined specifications (e.g., undamaged, appropriate volume, appropriate specimen type, appropriate disease indication) for acceptance for testing by the device test site in accordance with established procedures

Exclusion Criteria

The study participant's specimen is distributed to the device test site without a complete Test Request Form

Study participants will be excluded as a potential candidate for the pharmaceutical company-sponsored clinical trial by their physician based on the clinical trial exclusion criteria as assessed at screening visit 1

The study participant has not agreed to and signed the (Clinical Trial) Informed Consent Form

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Genotyping

Participants submit a blood specimen for APOL1 Genotyping CTA to identify high-risk genotypes

Approximately 1 year

Ongoing monitoring

Follow-up

Participants are monitored for safety and effectiveness after genotyping

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Synthetic Antisense Oligonucleotide

Trial Overview The trial is testing the accuracy of the APOL1 Genotyping Clinical Trial Assay, which uses blood samples to detect specific genetic markers associated with an increased risk of kidney disease.

How Is the Trial Designed?

Group I: APOL1 Genotyping Experimental Treatment 1 Intervention

All study participants will submit a blood specimen for APOL1 Genotyping CTA screening. The APOL1 Genotyping CTA will identify individuals who are homozygous or compound heterozygous for apolipoprotein L1 (APOL1) high-risk genotypes (G1 and G2). The individuals who are identified as being homozygous or compound heterozygous for the APOL1 high-risk genotypes are candidates for enrolment onto an pharmaceutical company-sponsored, Phase 2b clinical trial which is investigating the safety and efficacy of a synthetic antisense oligonucleotide (ASO) for the treatment of APOL1-mediated kidney disease (AMKD).

Who Is Running the Clinical Trial?

Almac Diagnostic Services LLC

Lead Sponsor

Trials

1

Recruited

1,000+

Published Research Related to This Trial

A new method using ultra-performance liquid chromatography and mass spectrometry has been developed to detect and quantify different forms of the ApoL1 protein in plasma, which is important for understanding kidney disease risk.

This method allows for the identification of individuals at risk for chronic kidney disease without needing DNA samples, making it valuable for early detection and potential treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid detection and quantification of apolipoprotein L1 genetic variants and total levels in plasma by ultra-performance liquid chromatography/tandem mass spectrometry. Zhou, H., Hoek, M., Yi, P., et al.[2019]

Research indicates that the APOL1 gene is linked to chronic kidney disease (CKD), particularly in individuals of recent African ancestry, and understanding its mechanisms could enhance kidney transplant safety and donor allocation.

Local production of the APOL1 renal-risk variant in the kidneys plays a significant role in nephropathy development, but not all individuals with high-risk genotypes will experience CKD, suggesting that environmental factors may be more influential than genetic interactions in determining kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of Injury in APOL1-associated Kidney Disease. Ma, L., Divers, J., Freedman, BI.[2022]

Not all individuals with the high-risk APOL1 genotype develop kidney disease, indicating that other factors may influence disease progression.

The study identifies several biomarkers associated with renal outcomes in high-risk APOL1 individuals, which could enhance risk assessment and understanding of APOL1 nephropathy mechanisms in precision medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Biomarking" the transition from genetic risk to kidney disease. Kruzel-Davila, E., Skorecki, K.[2022]

A new mouse model expressing human APOL1 gene allows for better study of APOL1-associated kidney disease, particularly in understanding how the G1 variant contributes to renal issues when combined with inflammatory triggers like IFN-γ.

The antisense oligonucleotide IONIS-APOL1Rx effectively reduced APOL1 expression and protected against kidney damage in APOL1 G1 mice, suggesting it could be a promising treatment for kidney diseases linked to APOL1 variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antisense oligonucleotide treatment ameliorates IFN-γ-induced proteinuria in APOL1-transgenic mice. Aghajan, M., Booten, SL., Althage, M., et al.[2020]

The apolipoprotein L1 gene (APOL1) significantly contributes to the higher risk of chronic kidney disease in African Americans, with two risk variants greatly increasing this risk.

In kidney transplantation, organs from deceased African American donors with two APOL1 risk variants have shorter survival rates, highlighting the importance of APOL1 genotyping in donor selection and kidney allocation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apolipoprotein L1 Gene Effects on Kidney Transplantation. Freedman, BI., Locke, JE., Reeves-Daniel, AM., et al.[2023]

APOL1 high-risk genotypes significantly increase the risk of chronic kidney disease, particularly in individuals of sub-Saharan African ancestry, highlighting the need for targeted treatment approaches.

Current treatments like hypertension control and immunosuppressive agents are not very effective, but new therapies such as small molecule inhibitors and antisense oligonucleotides show promise and warrant further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment potential in APOL1-associated nephropathy. Friedman, DJ., Ma, L., Freedman, BI.[2023]

African Americans are at a significantly higher risk (4-5 times) for developing kidney diseases, including those related to hypertension and focal segmental glomerulosclerosis, due to specific genetic factors.

Two variants in the APOL1 gene are linked to this increased risk, suggesting that understanding the APOL1 genotype could improve patient care and lead to new treatment strategies for kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APOL1 and kidney disease. Pollak, MR., Genovese, G., Friedman, DJ.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12361766/

APOL1 Mediated Kidney Disease: A Review and Look ... All participants had an estimated glomerular filtration rate > 27 mL/min/1.73m2 and the primary outcome was a change in urine protein to creatinine ratio from ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06839833

APOL1 Genotyping CTA Clinical Performance Study ... trial which is investigating the safety and efficacy of a synthetic antisense oligonucleotide (ASO) for the treatment of APOL1-mediated kidney disease (AMKD).

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468024923014626

Review Novel Therapies in APOL1-Mediated Kidney Disease This review summarizes key mechanistic insights in the pathogenesis of AMKD, emergent therapies, and discusses future challenges.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9263291/

Antisense oligonucleotides ameliorate kidney dysfunction in ... Administration of APOL1 ASO1 was effective even for established disease in the NEFTA-rtTA/TRE-G2APOL1 (NEFTA/G2APOL1) mice. We observed a strong correlation ...

5. withpower.com withpower.com/trial/phase-kidney-diseases-2-2025-c4508

APOL1 Genotyping for Kidney Disease The antisense oligonucleotide IONIS-APOL1Rx effectively reduced APOL1 expression and protected against kidney damage in APOL1 G1 mice, suggesting it could be a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10658239/

Novel Therapies in APOL1-Mediated Kidney Disease Apolipoprotein L1 (APOL1) high-risk variants confer an increased risk for the development and progression of kidney disease among individuals of recent ...

7. academic.oup.com academic.oup.com/ndt/article/39/Supplement_1/gfae069-0695-1003/7678711

1003 Safety, tolerability, pharmacokinetics, and ... APOL1 mediated kidney disease (AMKD) is associated with toxic gain of function variants in people of African ancestry carrying the high-risk ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2590059525000986

APOL1 Mediated Kidney Disease: A Review and Look ... Zhang et al reported that the number of recipient risk variant alleles was associated with an increased risk of death, censored allograft loss, and risk of ...