Study of LY3016859 in Participants With Diabetic Nephropathy

NCT01774981 | Completed Phase 1 Results

• 3 other identifiers: 14353I5V-MC-TGAB2012-004496-40
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this two-part study is to investigate the safety, tolerability and efficacy of LY3016859 after multiple intravenous (IV) dosing's in participants with diabetic nephropathy (DN). Part A will be dose escalation for safety and tolerability and Part B will evaluate Proteinuria.

Conditions

Diabetic Nephropathy

Outcome Measures

Primary Outcomes (2)

• Part B:Change From Baseline in Proteinuria

  Proteinuria is defined as the ratio of protein to creatinine.

  Baseline, 16 Weeks

• Part A and Part B: Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs

  Treatment-emergent adverse events (TEAEs) are events which were not present at baseline or pre-existing conditions at baseline that worsened in severity following the start of treatment. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.

  Baseline up to 32 Weeks

Secondary Outcomes (2)

• Part B: Change From Baseline in Proteinuria Over Time

  Baseline, 19 Weeks

• Part B: Change From Baseline in Albuminuria Over Time

  Baseline, 19 Weeks

Study Arms (8)

Placebo (Part A)

PLACEBO COMPARATOR

Part A: Placebo administered by 60 minute Intravenous (IV) infusion at Week 1 and Week 4.

Drug: Placebo

10 mg LY3016859 (Part A)

EXPERIMENTAL

Part A: 10 milligram (mg) LY3016859 administered by 60 minute IV infusion at Week 1 and Week 4.

Drug: LY3016859

100 mg LY3016859 (Part A)

EXPERIMENTAL

Part A: 100 mg LY3016859 administered by 60 minute IV infusion at Week 1 and Week 4.

Drug: LY3016859

750 mg LY3016859 (Part A)

EXPERIMENTAL

Part A: 750 mg LY3016859 administered by 60 minute IV infusion at Week 1 and Week 4.

Drug: LY3016859

Placebo (Part B)

PLACEBO COMPARATOR

Part B: Placebo administered by 60 minute IV infusion at Weeks 1, 4, 7, 10 and 13.

Drug: Placebo

50 mg LY3016859 (Part B)

EXPERIMENTAL

Part B: 50 mg LY3016859 administered by 60 minute IV infusion at Weeks 1, 4, 7, 10 and 13.

Drug: LY3016859

250 mg LY3016859 (Part B)

EXPERIMENTAL

Part B: 250 mg LY3016859 administered by 60 minute IV infusion at Weeks 1, 4, 7, 10 and 13.

Drug: LY3016859

750 mg LY3016859 (Part B)

EXPERIMENTAL

Part B: 750 mg LY3016859 administered by 60 minute IV infusion at Weeks 1, 4, 7, 10 and 13.

Drug: LY3016859

Interventions

Placebo DRUG

Administered IV

Placebo (Part A); Placebo (Part B)

LY3016859 DRUG

Administered IV

10 mg LY3016859 (Part A); 100 mg LY3016859 (Part A); 250 mg LY3016859 (Part B); 50 mg LY3016859 (Part B); 750 mg LY3016859 (Part A); 750 mg LY3016859 (Part B)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stable diabetic kidney disease (DKD) while taking Standard of Care medication (SOC), as defined by:
• Estimated glomerular filtration rate (eGFR) less than (\<) 90 milliliter per minute per 1.73 square meter (ml/min/1.73m²) as determine utilizing the Modification of Diet in Renal Disease (MDRD) equation
• Taking an angiotensin convertible enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) at a stable dose for greater than or equal to (≥) 2 months prior to randomization and agree to continue to take such throughout the duration of the study
• Type 1 or Type 2 diabetes on a stable treatment regimen and adequately controlled in the opinion of the investigator
• First morning protein-creatine ratio (PCR) at screening ≥400 milligrams per gram (mg/g) (Part B only)
• Clinical chemistry labs within acceptable range for the participant population, as per investigator judgment
• Men and women of non-childbearing potential as determined by medical history and physical examination
• Non-vasectomized male participants must agree to use a medically accepted method of contraception with all sexual partners during the study and for 90 days following the final dosing. Medically accepted effective forms of contraception may include condoms with contraceptive foam or having partners use diaphragms with contraceptive jelly or cervical caps with contraceptive jelly
• Female participants must be postmenopausal or surgically sterile to participate in this study. This is defined as females between age 45 to 75 years, inclusive, and either 12 months without a menstrual period \[no follicle stimulating hormone (FSH) test required\] or 6-12 months without a menstrual period and follicle stimulating hormone (FSH) greater than (\>) 40 international units per liter (IU/L)
• Must weigh ≥50 kilograms (kg) at time of screening and dosing
• Acceptable sitting blood pressure (BP) per the following American Heart Association (AHA) guidelines:
• Normal: systolic blood pressure (SBP) \<120 millimeters of mercury (mmHg) and diastolic blood pressure (DBP) \<80 mmHg
• Prehypertension: SBP 120-139 or DBP 80-89
• High Blood Pressure (Hypertension) Stage 1: SBP 140-159 mmHg or DBP 90-99
• Have given written informed consent prior to any study-specific procedures

You may not qualify if:

• Have a diagnosis of chronic kidney disease (CKD) other than DKD, (hypertensive nephrosclerosis superimposed on DKD is acceptable)
• Have SBP \>160 mmHg or DBP \>100 mmHg
• o Individuals with Stage 1 BP elevation (SBP 140-159 mmHg or DBP 90-99 mmHg) on some occasions during study, may be acceptable, as long as only non-protein-lowering antihypertensives are adjusted to achieve target BP goals (\<140/90 mmHg)
• Current use of (or within 2 weeks of enrollment), or projected need for a renin inhibitor or aldosterone antagonist, or a combination of Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB)
• Individuals in whom dialysis or transplantation is anticipated within 6 months of screening
• Have a history of acute kidney injury within 3 months of screening
• Are currently enrolled in, or discontinued within the last 60 days from, a clinical trial involving an investigational drug that has not received regulatory approval for any indication and/or have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives of the administered drug (whichever is longer) prior to dosing
• Have previously completed or withdrawn from this study or any other study investigating LY3016859
• Have a diagnosis of Class III or IV congestive heart failure (as defined by the New York Heart Association)
• Have an abnormality in the 12-lead Electrocardiogram (ECG) that, in the opinion of the investigator increases the risks associated with participating in the study. In addition, individuals with the following findings will be excluded:
• Confirmed corrected QT (QTcF) interval \>450 milliseconds (msec) for men and \>470 msec for women
• Irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular ectopic beats
• History of unexplained syncope
• Family history of unexplained sudden death or sudden death due to long QT syndrome
• T-wave configurations are not of sufficient quality for assessing QT interval, as determined by the investigator

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (7)

Innovative Research of West Florida

Clearwater, Florida, 33756, United States

Location

Creighton University Medical Center

Omaha, Nebraska, 68131, United States

Location

Northeast Clinical Research Center

Bethlehem, Pennsylvania, 18017, United States

Location

Southeast Renal Research Institute

Chattanooga, Tennessee, 37408, United States

Location

TAD Clinical Research

Lufkin, Texas, 75904, United States

Location

Renal Associates, PA

San Antonio, Texas, 78215, United States

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Sofia, 1612, Bulgaria

Location

MeSH Terms

Conditions

Diabetic Nephropathies

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLilly (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST_

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2013
• First Posted: January 24, 2013
• Study Start: March 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: September 19, 2019
• Results First Posted: August 15, 2017

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

US (6); BU (1)