Diabetic Nephropathy: Adults (age 18 - 90 years inclusive) with type 2 diabetes, an eGFR of 25-59 mL/min/1.73 m2, and with macroalbuminuria (>300 mg/g) will be randomized.
Conditions
Interventions
Product Name: MLN1202
Product Code: MLN1202
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: plozalizumab
CAS Number: 1610761-46-0
Current Sponsor code: MLN1202
Concen
Sponsors
Takeda Development Centre Europe Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject eligibility is determined according to the following criteria: 1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements. 2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. At the time of Screening the subject is male or female and aged 18-90 years inclusive at first dose of study medication. 4. The subject was previously diagnosed with type 2 diabetes mellitus per ADA criteria. 5. The subject has an estimated glomerular filtration rate based on serum creatinine (eGFR, determined by MDRD equation) of 25-59 mL/min/1.73 m(2) at Screening. 6. The subject has been on a stable dose of ACE inhibitor or ARB for 8 weeks prior to Screening. 7. The subject has residual albuminuria despite stable treatment with an ACE inhibitor or an ARB for at least 8 weeks prior to Screening (urine albumin:creatinine ratio [UACR] of > 300 mg/g creatinine, inclusive at Screening). 8. The subject has HbA1c test result less than or equal to 10.5% at screening. 9. Subject regularly using DPP4i or SGLT2 to treat diabetes has been on a stable dose and regimen within 2 months prior to Screening. 10. All patients who are not surgically sterile or post-menopausal, or whose partners are not surgically-sterile or postmenopausal, must use two effective birth control methods or abstain from intercourse during this study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 62 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 94
Exclusion criteria
Exclusion criteria: Any subject who meets any of the following criteria will not qualify for entry into the study: 1. Subject has received any investigational compound within 90 days prior to Screening. 2. The subject is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 3. Subject is taking any combination of dual RAS inhibition (such as an ACE inhibitor and an ARB or an ACE inhibitor and a mineralocorticoid receptor antagonist). 4. Subject has type 1 diabetes mellitus or a history of ketoacidosis. 5. Subject has poorly-controlled blood pressure (systolic blood pressure >160 or diastolic blood pressure >110, with blood pressure measured in the seated position after at least 5 minutes of rest) at Screening and Day 1. 6. Subject has received dialysis within 3 months of Screening. 7. Subject has infectious diseases or leg ulcers at Screening (all per discretion of Principal Investigator [PI]). 8. Subject has severe concurrent disease which, in the judgment of the investigator, would interfere significantly with the assessments of safety and efficacy during this study. 9. Subject with known infection with human immunodeficiency virus (HIV), or a positive test for Hepatitis B, Hepatitis C, or TB at Screening. 10. Subject has used long-term immune suppressants, steroid therapy (except for topical use or inhalation), chronic use of non-steroidal anti-inflammatory drug (NSAIDs), cyclooxygenase type 2 (COX-2) inhibitors within 2 weeks prior to Screening. Short-term use is defined as a duration of =4 weeks of continuous use. 11. In the judgment of the principal investigator, patients who are likely to be non-compliant or uncooperative during the study. 12. Subjects with known non-diabetic kidney disease (such as autosomal dominant polycystic kidney disease (ADPCKD), IgA nephropathy, focal segmental glomerulosclerosis, or obstructive uropathy). Hypertensive nephrosclerosis superimposed on diabetic kidney disease is acceptable. 13. Subject had a previous renal transplant. 14. Subject has hypersensitivity to other monoclononal antibodies (mAb) or to any component of the formulation of MLN1202. 15. The subject has history of malignancy within the previous 5 years (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin). 16. Subject is symptomatic with dysuria, and has a positive urine culture at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the effects of 85 days treatment with MLN1202 on urinary albumin-creatinine ratio (UACR) in subjects with type 2 diabetes, advanced kidney disease (diabetic nephropathy) and macro-albuminuria (UACR>300 mg/g) based on an average of 3 consecutive days first morning void sample collection.;Secondary Objective: Secondary Objectives: To characterize the effect of MLN1202 on urinary albumin-creatinine ratio over time. To characterize the effect of MLN1202 on total protein-creatinine ratio over time. Additional Objectives: To characterize the effect of study drug on glycosylated hemoglobin fraction (HbA1c); high sensitivity C-reactive protein (hs-CRP); homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function HOMA-BCF; and renal function, as measured by creatinine. To assess the safety and tolerability of study drug; evaluate the PK of MLN1202 given by SC injection in patients with CKD. To evaluate the correlation between genetic markers and the effect of MLN1202 on UACR; subject’s pain during weekly SC injections; the role of baseline urinary MCP-1 as a biomarker for the effect of MLN1202 on albuminuria.;Primary end point(s): Efficacy: The primary endpoint for this study is UACR at 85 days, relative to the baseline (average of 3 consecutive first in the morning urine voids). ;Timepoint(s) of evaluation of this end point: Day 85, relative to baseline average of 3 consecutive first in the morning voids | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints for this study are: • UACR change from baseline over time at Day 29, 57, 85, and 113, (these collections will be single first morning void with the exception of Day 85 and 113 which will use the average of 3 consecutive first morning voids). • Urinary protein:creatinine change from baseline over time at Day 29, 57, 85, and 113, relative to baseline. Additional Endpoints: • UACR change from baseline over time at Day 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 113 (these collections will be single first morning voids with the exception of Days 85 and 113 which will use the average of 3 consecutive first morning voids). • Change from Baseline in plasma glycosylated hemoglobin at Day 29, 57, 85, and 113. • Percent change from Baseline in serum hs-CRP at Day 29, 57, 85, and 113. • Change from Baseline in HOMA-IR and HOMA-BCF at Day 85. • Change from Baseline in serum creatinine at Day 29, 57, 85, and 113. • Change from Baseline in eGFR at Day 29, 57, 85, and 113. • The safety and tolerability of therapy will be assessed by collected AEs, labs, vital signs, physical examination, and electrocardiogram (ECG). • Pharmacokinetic parameters of MLN1202 in subjects with chronic kidney disease. • A 1-10 pain scale measures [Pain Assessment Scale, Appendix G] will be used to evaluate subject’s pain during weekly SC injections. Pharmacodynamic Endpoints: The following pharmacodynamic (PD) parameters will be determined: • Concentrations of MCP-1 in serum and urine. • Counts and relative percentages of monocyte and neutrophil populations (from differential white blood cell counts and flow cytometry of classical, inflammatory and intermediate monocytes, and mature, intermediate, and immature neutrophils in peripheral blood). • Change from Baseline in renal tumor necrosis factor alpha [TNF-a]. Immunogenicity Endpoints: • Proportion of patients with positive ADA (monthly) during the study. • Proportion of patient | — |
Countries
Austria, Denmark, Mexico, Peru, Serbia, Slovakia, South Africa, United States
Contacts
Public ContactMedical Director, Clinical Science
Takeda Development Centre Americas, Inc.
Outcome results
None listed