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A study of mirabegron in young children with neurogenic detrusor overactivity

Mirabegron in Young Children Study | Astellas Clinical Trials

A study to learn how [14C]ASP0367 is processed by the body in healthy men

14C ASP0367 In Males Study | Astellas Clinical Trials

A Study of Gilteritinib (ASP2215) Combined with Chemotherapy in Children, Adolescents and Young Adults with FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)

Gilteritnib and Chemotherapy Study | Astellas Clinical Trials

A study to find the best dose of ASP5354 to show lymph nodes in people with breast cancer or melanoma during surgery

ASP5354 to Show Lymph Nodes Study | Astellas Clinical Trials

A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)

Intravesical Enfortumab Vedotin for Bladder Cancer Study | Astellas Clinical Trials

A study of the safety and tolerability of ASP7317 in adults who are losing their clear, sharp central vision due to geographic atrophy secondary to dry age-related macular degeneration

ASP7317 for Geographic Atrophy Study | Astellas Clinical Trials

A Study to Assess the Antitumor Activity, Safety, Pharmacokinetics and Biomarkers of Zolbetuximab (IMAB362) in Participants with Claudin (CLDN) 18.2 Positive, Metastatic or Advanced Unresectable Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma

Zolbetuximab Study | Astellas Clinical Trials

A Study of an Intratumoral Oncolytic Virus in Patients with Advanced Metastatic Solid Tumors

Intratumoral Oncolytic Virus Study | Astellas Clinical Trials

A Study to Assess ASP0598 Otic Solution Following Topical Application in the Ear in Subjects with Chronic Tympanic Membrane Perforation (CTMP)

ASP058 Otic Solution Study | Astellas Clinical Trials

A study to evaluate ASP0367 in participants with primary mitochondrial myopathy

ASP0367 Study for Primary Mitochondrial Myopathy | Astellas Clinical Trials

A study of ASP2138 in adults with stomach cancer or pancreatic cancer

ASP2138 Study for Stomach or Pancreatic Cancer | Astellas Clinical Trials

A study about how ASP5354 affects the body in healthy adults and in adults whose kidneys do not work well

ASP5354 for Healthy Adults and Adults with Poor Kidneys | Astellas Clinical Trials

A Study for Subjects With Prostate Cancer Who Previously Participated in an Enzalutamide Clinical Study

Prostate Cancer Study for Previous Participation in Enzalutamide  | Astellas Clinical Trials

A Study to Assess the Efficacy and Safety of IMAB362 in Combination with Nab-Paclitaxel and Gemcitabine (Nab-P + GEM) as First Line Treatment in Subjects with Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma

IMAB362 with Nab P and GEM Study for Pancreatic Cancer  | Astellas Clinical Trials

A study of gilteritinib, venetoclax and azacitidine as a combined treatment for people newly diagnosed with acute myeloid leukemia

Gilteritinib Venetoclax and Azacitidine Study for Acute Myeloid Leukemia | Astellas Clinical Trials

A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects with Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)

ASP7517 for Acute Myeloid Leukimia | Astellas Clinical Trials

A study to evaluate ASP0367 in participants with reduced maximum oxygen uptake due to poor systemic oxygen extraction

ASP0367 for Reduced Maxiumum Oxygen Uptake Study | Astellas Clinical Trials

A study of ASP3082 in adults with previously treated solid tumors

ASP3082 for Solid Tumors Study | Astellas Clinical Trials

A Study of ASP1570 in adults with locally advanced or metastatic solid tumors

ASP1570 for Advanced or Metastatic Tumors Study | Astellas Clinical Trials

Study of ASP7517 Alone and with Pembrolizumab in Participants with Advanced Solid Tumors Expressing WT1 Antigen

ASP7517 with Pembrolizumab Study | Astellas Clinical Trials

A Safety Surveillance Study in Subjects with Macular Degenerative Disease Treated with Human Embryonic Stem Cell-derived Retinal Pigment Epithelial Cell Therapy

Macular Degenerative Disease Study | Astellas Clinical Trials

A study to evaluate mirabegron in pediatric participants from 5 to less than 18 years of age with overactive bladder (OAB)

Mirabegron Study in Children with OAB Study | Astellas Clinical Trials

Study of ASP0739 Alone and with Pembrolizumab in Advanced Solid Tumors with NY-ESO-1 Expression Participants

ASP0739 with Pembrolizumab Study For Solid Tumors| Astellas Clinical Trials

A study of ASP0367 in people with kidneys that do not work well and in healthy people

ASP0367 Study for Adults with Poor Kidneys | Astellas Clinical Trials

Enfortumab vedotin and pembrolizumab vs. chemotherapy alone in untreated locally advanced or metastatic urothelial cancer

Enfortumab Vedotin and Pembrolizumab vs Chemotherapy Study | Astellas Clinical Trials

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Have questions about or want more information about A Study of LY3471851 in Participants With Gastric Cancer? Contact us by filling out your information below and we’ll respond to you.

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Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development.  Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared.  Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Participants received tacrolimus extended release (Astagraf XL) at a starting dose of 0.15 milligram per kilogram (mg/kg), once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 nanogram per milliliter (ng/mL) at all times during the study.

Participants received tacrolimus immediate release as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.

idtx-ma-3004-clrrs-03-disc01-en-final-02 redacted csr synopsis.pdf

idtx-ma-3004-clls-disc01-en-final-02.pdf

NCT02723591_Prot_000.pdf

NCT02723591_SAP_001.pdf

This study compared the incidence of a two-part composite endpoint consisting of de novo donor specific antibody (DSA) formation or a designation of immune activation (IA) on peripheral blood molecular profiling in participants maintained on twice daily, immediate-release tacrolimus versus those maintained on Astagraf XL in the first year post-transplant.

To compare the effects of immediate-release tacrolimus and Astagraf XL on Donor-Specific Antibody (DSA) formation and the development of Immune Activation (IA) in de novo kidney transplant recipients

This was an exploratory, two year (shortened to 1 year due to a stopping rule necessitated by the adaptive design), prospective, randomized, multi-center, open-label trial examining long-term kidney transplant outcomes through the use of an adaptive design and a two-part, composite surrogate endpoint. Specifically, it was designed to compare the effects of twice daily, immediate-release tacrolimus and once daily Astagraf XL on DSA formation and the development of a peripheral blood molecular profile indicating the presence of IA in de novo kidney transplant recipients during the first year following transplantation. For the purposes of this study, IA was defined as a positive molecular signature using a molecular assay in all participants.

Participants were screened prior to surgery and randomized 1:1 to receive immediate-release tacrolimus, administered twice daily, or Astagraf XL, as a component of a standard immunosuppression maintenance regimen also consisting of corticosteroids (if given per institutional protocol) and mycophenolate mofetil (MMF) (or Myfortic® equivalent). Investigators were encouraged to start participants on the randomized study treatment (immediate release tacrolimus or Astagraf XL) within 48 hours of transplantation (pre-transplant administration of study treatment was not allowed). However, if medically indicated per the treating physician’s discretion, initiation of study treatment was delayed for up to seven days post-transplant.

CN CDE Number

EudraCT Number

jRCT Number

NCT ID

Patient Level Data

Product ST Name

Therapeutic Area

Link to results on the Astellas Clinical Study Results website.

Site US10023

Site US10037

Site US10002

Site US10020

Site US10021

Site US10001

Site US10005

Site US10014

Site US10029

Site US10027

Site US10003

Site US10028

Site US10031

Site US10016

Site US10013

Site US10022

Site US10036

Site US10019

Site US10018

Site US10012

Site US10008

Site US10010

Site US10007

Site US10026

Site US10032

Site US10004

Site US10024

Site US10006

Site US10035

Site US10025

Site US10030

Astagraf XL® to Understand the Impact of Immunosuppression on De Novo DSA Development and Chronic Immune Activation in Kidney Transplantation

Age Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The randomized set consisted of all participants who were randomized to receive the study drug (Astagraf XL or BID tacrolimus).

DSA was considered as a categorical (binary) variable with positivity determined at a threshold criteria approaching mean fluorescence intensity (MFI)=1000 at any time during the study. IA was considered either present or absent using the Trugraf™ v2.0 molecular assay. A negative designation (Trugraf TX Normal) was referred to as Immune Quiescence (IQ). Due to operating characteristics of the assay, a positive designation was considered evidence of IA in all participants.

Logistic regression with DSA/IA occurrence by Month 12 as response, with treatment group, planned Campath use, KDPI level (as recorded in IVRS), HLA Class II mismatch, recipient age, recipient gender, recipient race, and pre-transplant calculated panel reactivity antibody (cPRA) as fixed effects, and pooled site as a random effect with standard variance components covariance type.

The Modified Full Analysis Set (mFAS) consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.

Percentage of Participants who were Positive for de novo DSA (dnDSA) or Immune Activation (IA) Occurrence

Positive

Negative

Indeterminate

Unknown

DSA was considered as a categorical (binary) variable with positivity determined at a threshold criteria approaching MFI=1000 at any time during the study. Indeterminate was defined as MFI signal was >1000 and DSA was suspected, but could not be confirmed due to inadequate donor typing. Participants whose samples for the test were not available were reported as unknown.

The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.

Percentage of Participants who were Positive, Negative or Indeterminate for dnDSA Occurrence

Peak MFI of DSA positive participants was reported.

The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study. Only those mFAS participants who tested positive for dnDSA were included in the analyses.

Peak Mean Fluorescence Intensity (MFI) of DSA Positive Participants

Weak

Moderate

Strong

DSA was considered as a categorical (binary) variable with positivity determined at a threshold criteria approaching MFI=1000 at any time during the study.

P-values obtained from a 2x3 Exact Test of treatment by strength levels.

Percentage of DSA Positive Participants with Weak, Moderate and Strong Antibody Strentgh

DSA was regarded as persistent under the following conditions: (i) DSA was detected and remained above the threshold for positivity (MFI = 1000) for two consecutive or nonconsecutive measurements, or (ii) the new appearance of a DSA at the threshold for positivity when preceded by a DSA of a different specificity that had subsequently become non-detectable.

Percentage of DSA Positive Participants with DSA Persistence

Percentage of participants who were positive or negative for C1q-binding DSA were reported.

Percentage of Participants who were Positive or Negative for Complement Component 1, Q Subcomponent (C1q)-binding DSA

Percentage of participants who were positive or negative for IgG3 isotype were reported.

Percentage of Participants who were Positive or Negative for DSA Immunoglobulin G (IgG3) Isotype

Percentage of DSA positive participants with HLA-DQ Class-II were reported.

The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study. Only those mFAS participants who tested positive for DSA were included in the analyses.

Percentage of DSA Positive Participants with Human Leukocyte Antigen, Class II, DQ Locus (HLA-DQ)

IA was considered either present or absent using the Trugraf™ v2.0 molecular assay. A negative designation (Trugraf TX Normal) was referred to as Immune Quiescence (IQ). Due to operating characteristics of the assay, a positive designation was considered evidence of IA in all participants.

Logistic regression with IA occurrence by Month 12 as response, with treatment group, planned Campath use, KDPI level (as recorded in IVRS), HLA Class II mismatch, recipient age, recipient gender, recipient race, and pre-transplant cPRA as fixed effects, and pooled site as a random effect with standard Variance Components covariance type.

Percentage of Participants who were Positive for IA Occurrence from Day 1 to Day 365 visit

Percentage of Participants who were Positive for IA Occurrence from Day 30 to Day 365 visit

IA was regarded as persistent under the following conditions: (i) IA was detected and remained above the threshold for positivity for two consecutive or non-consecutive measurements, or (ii) the new appearance of an IA at the threshold for positivity when preceded by an IA of a different specificity that had subsequently become non-detectable.

Percentage of Participants with IA Persistence

TG was defined as chronic glomerulopathy (cg) >0 on centrally-interpreted institutional protocol biopsy or biopsy obtained for cause during the first year post-transplant with +2 months visit window.

P-values obtained from a 2-sided Fisher's Exact Test of treatment arm by response.

The Biopsy Analysis Dataset (BAS) consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.

Percentage of Participants with Presence of Transplant Glomerulopathy (TG) on Biopsy

MI was defined as glomerulitis (g) + peritubular capillaritis (ptc)>=2 on centrally-interpreted institutional protocol biopsy or biopsy obtained for cause during the first year post-transplant, with +2 months visit window.

The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.

Percentage of Participants with Presence of Microcirculatory Inflammation (MI) on Biopsy

IFTA and inflammation was defined as IFTA positive and inflammation positive (i >0) on centrally-interpreted institutional protocol biopsy or biopsy obtained for cause during the first year posttransplant, with +2 months visit window.

Percentage of Participants with Presence of Interstitial Fibrosis and Tubular Atrophy (IFTA) and Inflammation on Biopsy

The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.

Percentage of Participants with Estimated Glomerular Filtration Rate (eGFR) Threshold of <30 Millimetre per Minute per 1.73 Meter Square (mL/min/1.73m^2)

The eGFR was calculated using the MDRD formula.

Percentage of Participants with eGFR Threshold of <40 mL/min/1.73m^2

Logistic regression with occurrence of eGFR < 50 by Month 12 as response, with treatment group, planned Campath use, KDPI level (as recorded in IVRS), HLA Class II mismatch, recipient age, recipient gender, recipient race, and pre-transplant cPRA as fixed effects, and pooled site as a random effect with standard Variance Components covariance type.

Percentage of Participants with eGFR Threshold of <50 mL/min/1.73m^2

Logistic regression with occurrence of 5-point eGFR decline by Month 12 as response, with treatment group, planned Campath use, KDPI level (as recorded in IVRS), HLA Class II mismatch, recipient age, recipient gender, recipient race, and pre-transplant cPRA as fixed effects, and pooled site as a random effect with standard Variance Components covariance type.

Percentage of Participants with a Five-point Decline in eGFR

Day 30

Day 90

Day 180

Day 270

Day 365

The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study. mFAS population with available data at each time point.

eGFR at Day 30, Day 90, Day 180, Day 270 and Day 365

Graft loss was defined as re-transplantation, transplant nephrectomy, or a return to dialysis for at least a six week duration, or participants' death.

Percentage of Participants with Graft Loss

Percentage of participants who died were reported.

Percentage of Participants who Died

Positivity was determined by local biopsy, central pathology, or reported adverse events.

Percentage of Participants with Biopsy-Proven Acute Rejection (BPAR)

Percentage of participants who were lost to follow-up were reported.

Percentage of Participants who were Lost to Follow-up

Percentage of participants with either graft loss, death, BPAR or lost to follow-up were reported.

Percentage of Participants with Either Graft Loss, Death, BPAR or Lost to Follow-up

Percentage of participants with ABMR were reported. Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. A positive assessment is defined as antibody mediated changes that are diagnosed as either acute ABMR or chronic active ABMR.

Percentage of Participants with any Antibody–Mediated Rejection (ABMR)

Percentage of participants with normal biopsy findings were reported.

Percentage of Participants with Normal Biopsy Findings

Percentage of participants with C4d deposition without active rejection were reported.

The BAS consisted of all mFAS participants who had at least 1 posttransplant central pathology assessment.

Percentage of Participants with C4d Deposition without Active Rejection

Percentage of participants with acute ABMR were reported.

Percentage of Participants with Acute ABMR

Grade I

Grade II

Grade III

Percentage of participants with grade I, II and III acute ABMR were reported. Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Acute ABMR was graded as Grade I: acute tubular necrosis-like -like minimal inflammation, Grade II: Capillary and or glomerular inflammation (ptc/g >0) and/or thromboses, and Grade III: arterial - v3.

The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment. Only those BAS participants who had acute AMBR were included in the analyses.

Percentage of Participants with Grade I, II and III Acute ABMR

Percentage of participants with chronic ABMR were reported.

Percentage of Participants with Chronic ABMR

Percentage of participants with borderline changes were reported.

Percentage of Participants with Borderline Changes

Percentage of participants with acute TCMR were reported.