APOL1 Genotyping for Kidney Disease
Recruiting in Palo Alto (17 mi)
Overseen byRichard Kennedy, MD PhD FRCP
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Almac Diagnostic Services LLC
Disqualifiers: Incomplete consent, Specimen issues, others
No Placebo Group
Trial Summary
What is the purpose of this trial?Clinical Performance Study SP2024001, is a prospective, interventional study to assess the clinical performance of the APOL1 Genotyping Clinical Trial Assay (CTA) in the intended use population and environment. The study will use the APOL1 Genotyping CTA to test deoxyribonucleic acid (DNA) extracted from blood specimens to 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).
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 the Synthetic Antisense Oligonucleotide treatment safe for humans?
Research on a treatment called IONIS-APOL1Rx, a type of Synthetic Antisense Oligonucleotide, showed it was effective in mice for reducing kidney problems related to the APOL1 gene. However, there is no specific safety data available for humans yet, so more studies are needed to confirm its safety in people.
12345How does the drug Synthetic Antisense Oligonucleotide differ from other treatments for APOL1-related kidney disease?
This drug is unique because it targets the APOL1 gene directly, using antisense oligonucleotides (short DNA or RNA molecules) to reduce the production of harmful proteins linked to kidney disease, offering a personalized approach for those with specific genetic risk factors.
23567Eligibility Criteria
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
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
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
+1 more
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
+1 more
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: APOL1 GenotypingExperimental Treatment1 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).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Almac Diagnostic Services LLCDurham, NC
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Who Is Running the Clinical Trial?
Almac Diagnostic Services LLCLead Sponsor
References
Mechanisms of Injury in APOL1-associated Kidney Disease. [2022]An improved understanding of the pathogenesis in apolipoprotein L1 (APOL1) gene-associated chronic kidney disease (CKD) arose from observations in kidney transplantation. APOL1 genotyping could soon improve the safety of living kidney donation in individuals with recent African ancestry and alter the allocation of deceased donor kidneys.
Antisense oligonucleotide treatment ameliorates IFN-γ-induced proteinuria in APOL1-transgenic mice. [2020]African Americans develop end-stage renal disease at a higher rate compared with European Americans due to 2 polymorphisms (G1 and G2 risk variants) in the apolipoprotein L1 (APOL1) gene common in people of African ancestry. Although this compelling genetic evidence provides an exciting opportunity for personalized medicine in chronic kidney disease, drug discovery efforts have been greatly hindered by the fact that APOL1 expression is lacking in rodents. Here, we describe a potentially novel physiologically relevant genomic mouse model of APOL1-associated renal disease that expresses human APOL1 from the endogenous human promoter, resulting in expression in similar tissues and at similar relative levels as humans. While naive APOL1-transgenic mice did not exhibit a renal disease phenotype, administration of IFN-γ was sufficient to robustly induce proteinuria only in APOL1 G1 mice, despite inducing kidney APOL1 expression in both G0 and G1 mice, serving as a clinically relevant "second hit." Treatment of APOL1 G1 mice with IONIS-APOL1Rx, an antisense oligonucleotide (ASO) targeting APOL1 mRNA, prior to IFN-γ challenge robustly and dose-dependently inhibited kidney and liver APOL1 expression and protected against IFN-γ-induced proteinuria, indicating that the disease-relevant cell types are sensitive to ASO treatment. Therefore, IONIS-APOL1Rx may be an effective therapeutic for APOL1 nephropathies and warrants further development.
"Biomarking" the transition from genetic risk to kidney disease. [2022]Only some individuals carrying the high-risk APOL1 genotype go on to develop kidney disease phenotypes. In this issue of Kidney International, Nadkarni and colleagues report the associations of several biomarkers with renal outcomes in individuals with high-risk APOL1 genotypes. In the era of precision medicine, these findings should translate into improved longitudinal risk assessment for this high-risk population and might also provide additional insights regarding sites and mechanisms of APOL1 nephropathy.
Treatment potential in APOL1-associated nephropathy. [2023]More than 5 million African-Americans, and millions more in Africa and worldwide, possess apolipoprotein L1 gene (APOL1) high-risk genotypes with an increased risk for chronic kidney disease. This manuscript reviews treatment approaches for slowing the progression of APOL1-associated nephropathy.
Apolipoprotein L1 Gene Effects on Kidney Transplantation. [2023]The pathogenesis of many common etiologies of nephropathy has been informed by recent molecular genetic breakthroughs. It now is apparent that the ethnic disparity in the risk for nondiabetic chronic kidney disease between African Americans and European Americans is explained largely by variation in the apolipoprotein L1 gene (APOL1). The presence of two APOL1 renal risk variants markedly increases an individual's risk for kidney disease. In transplantation, kidneys from deceased African Americans with two APOL1 renal risk variants have shorter survival intervals after engraftment, regardless of the ethnicity of the recipient. Precision medicine will transform the clinical practice of nephrology and kidney transplantation, and play an important role in the allocation of kidneys from deceased and living kidney donors with recent African ancestry. This article reviews existing data on APOL1 in deceased-donor and living-donor kidney transplantation. It considers the impact of including APOL1 genotyping in decisions on the allocation and discard of deceased-donor kidneys, as well as the selection of living donors.
APOL1 and kidney disease. [2022]We review recent work on the genetic basis of kidney disease in African Americans and its relationship to variation in the APOL1 gene.
Rapid detection and quantification of apolipoprotein L1 genetic variants and total levels in plasma by ultra-performance liquid chromatography/tandem mass spectrometry. [2019]Human genetics studies in African Americans have shown a strong correlation between polymorphisms in the ApoL1 gene and chronic kidney disease (CKD). To gain further insight into the etiology of ApoL1-associated kidney diseases, the determination of circulating levels of both wild type as well as ApoL1 variants could be of significant use. To date, antibodies that discriminate between all three ApoL1 variant forms (wild type, G1 and G2) are not available. We aimed to develop a rapid method for detecting and quantifying ApoL1 variants and total levels in plasma.