MLN1202 75, 105, 150 mg as add-on to ACE/ARB to treat Diabetic Nephropathy

• Conditions: 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.; MedDRA version: 18.0Level: PTClassification code 10061835Term: Diabetic nephropathySystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2014-005142-21-DK
• Lead Sponsor: Takeda Development Centre Europe Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-16
• Last Update Posted: 14 March 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 156

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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified