Clinical trial NCT02358096: A Study to Evaluate ASP8232 as Add-On Therapy to Angiotensin Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) in Reducing Albuminuria in Patients With Type 2 Diabetes and Chronic Kidney Disease
Official title: A Phase 2, Double-Blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of ASP8232 as Add-On Therapy to Angiotensin Converting Enzyme Inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) in Reducing Albuminuria in Patients With Type 2 Diabetes and Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Type 2 Diabetes
Keywords: Chronic Kidney Disease
Type 2 Diabetes
ASP8232
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2015-02-06
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of ASP8232 in reducing Urinary Albumin to Creatinine Ratio (UACR) in subjects with Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD) at 12 weeks compared to placebo.


Eligibility criteria: Inclusion Criteria:

* Subject must have an estimated glomerular filtration rate (eGFR) ) \>=25 and \<75 ml/min/1.73m2.
* Subject must have a documented diagnosis of T2DM and received anti-diabetic medication (oral and/or parenteral) for at least 1 year prior to screening
* Subject's glycated hemoglobin (HbA1c) level is \< 11.0% (\<97 mmol/mol) at screening.
* Subject is on a stable therapy with an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB) for at least 3 months prior to screening.
* Subject who receives anti-hypertensive treatment, non-insulin anti-diabetic agents and/or vitamin D receptor activators at screening needs to be on stable therapy for at least 3 months prior to screening. Subjects on insulin therapy may have the insulin type/dose/schedule adjusted even during the 3 months prior to screening.
* If the subject has been subjected to specific dietary interventions then this has to be stable over the past 3 months prior to screening visit.
* Subject's UACR is ≥ 200 and ≤ 3000 mg/g in a first morning void (FMV) sample at screening AND the geometric mean UACR of all FMV samples at visit 4 and at visit 5 is ≥ 200 and ≤ 3000 mg/g AND the UACR in at least 3 FMV samples at visit 4 and visit 5 is ≥ 200 mg/g.

Exclusion Criteria:

* Subject is on, or previously received, renal replacement therapy (e.g. dialysis or kidney transplantation).
* Subject has obstructive uropathy or other causes of renal impairment not related to parenchymal renal disorder and/or disease of the kidney; or subject currently has or has had in the past renal disease secondary to malignancy.
* Subject's renal impairment and/or albuminuria is considered to be of other origin than Diabetic Kidney Disease.
* Subject has known (auto-) immune disorder and/or received immunosuppression for more than 2 weeks, cumulatively, within 12 weeks prior to screening or anticipated need for immuno-suppressive therapy during the study.
* Subject has active urinary tract infection which requires treatment or clinically significant infection at the time of screening or randomization
* Subject is diagnosed with type 1 diabetes mellitus or diabetes mellitus with unclear etiology.
* Subject has a sitting systolic blood pressure (SBP) \<90 or \>160 mmHg and/or a diastolic blood pressure (DBP) \>90 mmHg at screening.

Primary outcomes:
measure: Mean change of log transformed urinary albumin to creatinine ratio (UACR) from baseline to end of treatment
timeFrame: Baseline and end of treatment (12 weeks)
Secondary outcomes:
measure: Proportion of subjects with either >30% or >40% or >50% reduction in UACR from baseline to end of treatment
timeFrame: Baseline and end of treatment (12 weeks)
measure: Mean change of log transformed albumin excretion rate (AER) from baseline to end of treatment
timeFrame: Baseline and end of treatment (12 weeks)
measure: Proportion of subjects with either >30% or >40% or >50% reduction in AER from baseline to end of treatment
timeFrame: Baseline and end of treatment (12 weeks)
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: Site CZ42002
city: Ceské Budejovice
country: Czechia
facility: Site CZ42003
city: Prague 4
country: Czechia
facility: Site CZ42001
city: Praha 10
country: Czechia
facility: Site CZ42005
city: Praha 9
country: Czechia
facility: Site CZ42004
city: Copenhagen
country: Denmark
facility: Site DK45016
city: Gentofte
country: Denmark
facility: Site DK45004
city: Herlev
country: Denmark
facility: Site DK45001
city: Hillerød
country: Denmark
facility: Site DK45002
city: Holsterbro
country: Denmark
facility: Site DK45007
city: Viborg
country: Denmark
facility: Site DK45006
city: Berlin
country: Germany
facility: Site DE49004
city: Düsseldorf
country: Germany
facility: Site DE49002
city: Elsterwerda
country: Germany
facility: Site DE49008
city: Heidelberg
country: Germany
facility: Site DE49003
city: Balatonfüred
country: Hungary
facility: Site HU36002
city: Budapest
country: Hungary
facility: Site HU36016
city: Budapest
country: Hungary
facility: Site HU36010
city: Hatvan
country: Hungary
facility: Site HU36003
city: Kaposvar
country: Hungary
facility: Site HU36012
city: Szekesfehervar
country: Hungary
facility: Site HU36017
city: Szigetvar
country: Hungary
facility: Site HU36007
city: Szikszó
country: Hungary
facility: Site HU36005
city: Veszprem
country: Hungary
facility: Site HU36018
city: Bergamo
country: Italy
facility: Site IT39007
city: Pavia
country: Italy
facility: Site IT39005
city: Piacenza
country: Italy
facility: Site IT39002
city: Rome
country: Italy
facility: Site IT39012
city: Turin
country: Italy
facility: Site IT39004
city: Rotterdam
country: Netherlands
facility: Site NL31004
state: Zuid-Holland
city: Dordrecht
country: Netherlands
facility: Site NL31001
city: Hoogeveen
country: Netherlands
facility: Site NL31003
city: Lodz
country: Poland
facility: Site PL48026
city: Lodz
country: Poland
facility: Site PL48008
city: Lodz
country: Poland
facility: Site PL48004
city: Oświęcim
country: Poland
facility: Site PL48027
city: Plock
country: Poland
facility: Site PL48003
city: Poznan
country: Poland
facility: Site PL48001
city: Radom
country: Poland
facility: Site PL48022
city: Rzeszow
country: Poland
facility: Site PL48006
city: Sopot
country: Poland
facility: Site PL48005
city: Torun
country: Poland
facility: Site PL48002
city: Warszawa
country: Poland
facility: Site PL48025
city: Barcelona
country: Spain
facility: Site ES34001
city: Barcelona
country: Spain
facility: Site ES34005
city: Barcelona
country: Spain
facility: Site ES34004
city: Barcelona
country: Spain
facility: Site ES34002
city: Ciudad Real
country: Spain
facility: Site ES34007
city: Lugo
country: Spain
facility: Site ES34006
city: Madrid
country: Spain
facility: Site ES34008
city: Madrid
country: Spain
facility: Site ES34012
city: Majadahonda
country: Spain
facility: Site ES34010
city: Palma de Mallorca
country: Spain
facility: Site ES34003
city: Burton-on-Trent
country: United Kingdom
facility: Site GB44004
city: Chester
country: United Kingdom
facility: Site GB44001
city: London
country: United Kingdom
facility: Site GB44005
city: South Yorkshire
country: United Kingdom
facility: Site GB44003
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Executive Director
role: STUDY_DIRECTOR
References:
citation: de Zeeuw D, Renfurm RW, Bakris G, Rossing P, Perkovic V, Hou FF, Nangaku M, Sharma K, Heerspink HJL, Garcia-Hernandez A, Larsson TE. Efficacy of a novel inhibitor of vascular adhesion protein-1 in reducing albuminuria in patients with diabetic kidney disease (ALBUM): a randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2018 Dec;6(12):925-933. doi: 10.1016/S2213-8587(18)30289-4. Epub 2018 Nov 6.