Efficacy and Safety of Weekly Subcutaneous MLN1202 in Improving Diabetic Nephropathy in Participants With Macroalbuminuria

NCT02410499 | Withdrawn Phase 2 DMC

• 3 other identifiers: MLN1202-20052014-005142-21U1111-1168-1426
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to characterize the effects of 85 days treatment with MLN1202 on urinary albumin-to-creatinine ratio (UACR) in participants with type 2 diabetes, advanced kidney disease/diabetic nephropathy (DN) and macro-albuminuria (UACR\>300 mg/g) based on average of 3 consecutive first morning voids sample collection.

Conditions

Diabetic Nephropathy

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) at Day 85

  UACR will be calculated using the geometric mean of 3 consecutive days first in the morning urine voids. First morning void is defined as a void upon awakening and before beginning daily activities.

  Baseline and Day 85

Secondary Outcomes (2)

• Change from Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Over Time

  Baseline and Days 29, 57, 85, and 113

• Change from Baseline in Urinary Protein:Creatinine Ratio (UPCR) Over Time

  Baseline and Days 29, 57, 85, and 113

Study Arms (4)

Placebo

PLACEBO COMPARATOR

MLN1202 placebo-matching solution, subcutaneous injection (SC), once, on Day 1 (loading dose), followed by MLN1202 placebo-matching solution, SC, once, weekly, on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

Drug: MLN1202 Placebo

MLN1202 75 mg

EXPERIMENTAL

MLN1202 450 mg, solution, SC injection, once, on Day 1 (loading dose), followed by MLN1202 75 mg, solution, SC, once, weekly, on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

Drug: MLN1202

MLN1202 105 mg

EXPERIMENTAL

MLN1202 450 mg, solution, SC injection, once, on Day 1 (loading dose), followed by MLN1202 105 mg, solution, SC, once, weekly, on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

Drug: MLN1202

MLN1202 150 mg

EXPERIMENTAL

MLN1202 450 mg, solution, SC injection, once, on Day 1 (loading dose), followed by MLN1202 150 mg, solution, SC, once, weekly, on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

Drug: MLN1202

Interventions

MLN1202 Placebo DRUG

MLN1202 placebo-matching solution for SC injection

Placebo

MLN1202 DRUG

MLN1202 solution for SC injection

MLN1202 105 mg; MLN1202 150 mg; MLN1202 75 mg

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, the participant is capable of giving informed consent to enter the trial, including understanding and complying with protocol requirements.
• The participant or, when applicable, (eg, where the subject is capable of giving verbal informed consent to enter the trial but cannot physically sign a written, informed consent form), the participant'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.
• At the time of Screening the participant is male or female and aged 18-90 years inclusive at first dose of study medication.
• Was previously diagnosed with type 2 diabetes mellitus per American Diabetes Association criteria.
• Has an estimated glomerular filtration rate (eGFR) based on serum creatinine (eGFR, determined by Modification of Diet in Renal Disease \[MDRD\] equation) of 25-59 mL/min/1.73 m(2) at Screening.
• Has been on a stable dose of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) for 8 weeks prior to Screening.
• Has residual albuminuria despite stable treatment with an ACE inhibitor or an ARB for at least 8 weeks prior to Screening (albumin:creatinine ratio \[ACR\] of \> 300 mg/g creatinine, inclusive at Screening).
• Has glycosylated hemoglobin (HbA1c) less than or equal to 10.5% at screening.
• If a subject is regularly using dipeptidyl peptidase-4 inhibitor (DPP-4i) or sodium-glucose cotransporter 2 inhibitor (SGLT2i) to treat diabetes, he/she has been on a stable dose and regimen within 2 months prior to Screening.
• All participants 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.

You may not qualify if:

• Has received any investigational compound within 90 days prior to Screening.
• 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.
• Is taking any combination of dual renin-angiotensin system (RAS) inhibition (such as an ACE inhibitor and an ARB or an ACE inhibitor and a mineralocorticoid receptor antagonist).
• Has type 1 diabetes mellitus or a history of ketoacidosis.
• 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.
• Has received dialysis within 3 months of Screening.
• Has infectious diseases or leg ulcers at Screening (all per discretion of Principal Investigator \[PI\]).
• Has severe concurrent disease which, in the judgment of the investigator, would interfere significantly with the assessments of safety and efficacy during this study.
• Has known infection with human immunodeficiency virus (HIV), or a positive test for Hepatitis B, Hepatitis C, or tuberculosis (TB) at Screening. Subjects who have a positive TB skin test at Screening must rule out active or latent tuberculosis documented by chest x-ray in order to be considered eligible for study participation.
• 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.
• In the judgment of the principal investigator, participants who are likely to be non-compliant or uncooperative during the study.
• Has known non-diabetic kidney disease (such as autosomal dominant polycystic kidney disease (ADPCKD), Immunoglobulin A (IgA) nephropathy, focal segmental glomerulosclerosis, or obstructive uropathy). Hypertensive nephrosclerosis superimposed on diabetic kidney disease is acceptable.
• Had a previous renal transplant.
• Has hypersensitivity to other monoclonal antibodies (mAb) or to any component of the formulation of MLN1202.
• Has history of malignancy within the previous 5 years (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin).

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

plozalizumab

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2015
• First Posted: April 7, 2015
• Study Start: May 20, 2015
• Primary Completion: November 17, 2015
• Study Completion: November 17, 2015
• Last Updated: September 25, 2017

Record last verified: 2017-09