Trial · NCT07539454
Registered outcomes13
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
1 to 13 of 13
Download this page as JSON| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Overall response rate (ORR) | Up to 5 years after completion of study treatment | The ORR will be estimated for each dose group and for all groups combined. The 95% confidence intervals will be constructed for the ORR. |
| Secondary | Incidence of adverse events (AEs) | Up to 5 years after completion of study treatment | The AEs will be tabulated by type, grade, and attribution. |
| Secondary | Duration of the response (DOR) | From the first date on which a partial response or complete response is documented until progression or death due to any cause, assessed up to 5 years after completion of study treatment | Non-responders will be excluded in DOR analysis. Participants who begin treatment but drop out prior to the first post-baseline response assessment will be considered non-responders. The Kaplan-Meier method will be used to describe the DOR for all treated participants. The proportional hazards model will be used to evaluate the association of HIV status and pretreatment status on the DOR. |
| Secondary | Cumulative proportion of study participants still in response | At 1 year | Will be estimated using the point estimate and the 95% confidence interval using Greenwood's formula for the standard error of the Kaplan-Meier estimate. |
| Secondary | Blood biomarkers | Up to 5 years after completion of study treatment | Will assess the effect of nirogacestat on blood biomarkers such as CD4+ and CD8+ T, CD19+, cell number, HIV and Kaposi sarcoma-associated herpesvirus virus load. The analysis of variance will be used to evaluate the changes from entry to 4 or 12 weeks in CD4 and CD8 cell counts and percentages and levels of plasma-associated HIV-1 ribonucleic acid (RNA). Descriptive statistics for biomarkers will be reported using mean, standard deviation, median, and range. Linear regression analysis and correlation coefficient analysis will be performed to examine the association between change from baseline in a specific biomarker and study covariates. |
| Secondary | Levels of Notch target and regulatory gene products | Baseline up to 5 years after completion of study treatment | Will assess baseline levels of Notch target and regulatory gene products as a target of Nirogacestat activity. Notch target and regulatory gene expression at baseline will be summarized using descriptive statistics, and data visualization will be performed using principal component analysis and T-distributed stochastic neighbor embedding (t-SNE) plots. Linear and generalized linear models will be used to examine the association between expression level and study covariates. When multiplicity adjustment is needed, Bonferroni correction and false discovery rate approaches will be considered. |
| Other | Tumor-associated Kaposi sarcoma-associated herpesvirus (KSHV) latent and lytic gene expression | Up to 5 years after completion of study treatment | Will assess the effect of Nirogacestat on tumor-associated KSHV latent and lytic gene expression. To evaluate the relationship between clinical response and quantitative measures of KSHV/human herpesvirus (HHV)-8 and HIV viral load, these measures will be tested to determine if they are normally distributed. If the data does not meet the assumptions of normality, the data will be transformed for analysis purposes. Analysis of variance will be used to assess the relationship between qualification of baseline levels of KSHV/HHV-8, HIV viral load, and response. Spearman rank correlation analysis will be used to evaluate the relationship between the qualification of baseline KSHV/HHV-8, HIV viral load and time to progression, and response duration. |
| Other | Activation of Notch target genes and Notch regulatory genes | Up to 5 years after completion of study treatment | Will assess effects of Nirogacestat on activation of Notch target genes and Notch regulatory genes. |
| Other | Tumor-associated endothelial-mesenchymal transition | At the end of Cycle 1 (each cycle is 28 days) | Will assess effects of Nirogacestat on tumor-associated endothelial-mesenchymal transition. Endothelial-mesenchymal transition will be assessed from scRNAseq. The following markers will be measured. Endothelial markers decreasing over time: CDH5 (VE-cadherin), PECAM1 (CD31), VWF (von Willebrand Factor), TEK (TIE2); Mesenchymal markers increasing over time: ACTA2 (a-SMA), VIM (vimentin), S100A4 (FSP-1), FN1 (Fibronectin); Master regulators of EMT increasing over time: SNAI1 (Snail), SNAI2 (Slug), TWIST1, ZEB1, ZEB2, LEF1. |
| Other | Peak plasma of Nirogacestat in KS patients | Cycle 1 pre-dose, 0.5, 1.5, and 3 hours post-first dose and Cycle 2 day 1, pre-dose (one cycle=28 days) | For pharmacokinetic analysis, 20 samples will be used (10 from responders and 10 from non-responders) to estimate peak plasma level. |
| Other | AUCs of Nirogacestat in KS patients | Cycle 1 pre-dose, 0.5, 1.5, and 3 hours post-first dose and Cycle 2 day 1, pre-dose (one cycle=28 days) | For pharmacokinetic analysis, 20 samples will be used (10 from responders and 10 from non-responders) to estimate area under the curve (AUC)s such as AUC0-last and AUC0-∞, clearance, half-life, time of maximum concentration, and concentration maximum. |
| Other | Tissue biomarkers at progression by single cell transcriptomics or single cell RNA sequencing (scRNAseq) | Up to 5 years after completion of study treatment | Will assess effects of Nirogacestat on tissue biomarkers at progression by single cell transcriptomics or scRNAseq. Descriptive statistics will be used for results of scRNAseq for 20 samples (10 samples from responders and 10 samples from non-responders). Differential expression analysis will be performed and visualization using volcano plot, boxplot, t-SNE will be displayed. |
| Other | Tissue biomarkers by multiplex immunohistochemistry (IHC) | Baseline and after 28 days of therapy | Will assess effects of Nirogacestat on tissue biomarkers by multiplex IHC. Descriptive statistics will be used for results of multiplex IHC for 20 samples (10 samples from responders and 10 samples from non-responders). Differential expression analysis will be performed and visualization using volcano plot, boxplot, t-SNE will be displayed. For multiplexed IHC analysis, mean fluorescent intensity for each biomarker will be obtained by time point and change from baseline will be calculated and summarized using descriptive statistics. |
Source ClinicalTrials.govtrials-2026-11-12-0.5.0
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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