A Study of NKTR-358 (LY3471851) in Participants With Systemic Lupus Erythematosus (SLE)

NCT03556007 | Completed Phase 1 FDA Drug

• 3 other identifiers: 17238J1P-MC-KFAB17-358-02
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 14

Brief Summary

The main purpose of this study is to evaluate the safety and tolerability of a study drug known as LY3471851 in participants with SLE. The study will last about 79 days for each participant.

Conditions

Systemic Lupus Erythematosus

Keywords

T regulatory cells

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of LY3471851 - Number of Participants Experiencing Adverse Events

  Safety and tolerability of LY3471851 as assessed through collection of adverse events, serious adverse events, change in vital signs (body temperature, blood pressure, heart rate, rate of breathing and oxygen in blood); electrocardiograms (ECG); laboratory evaluations (hematology, chemistry, liver function and urine analysis).

  Informed consent until last study visit (approximately 79 days after first dose of study drug)

Secondary Outcomes (20)

• Pharmacokinetics (PK): Area Under the Drug Concentration - Time Curve from Zero to the End of Dosing Interval (i.e, 14 days past each dose) (AUC[0-Day 14]) of LY3471851

  Baseline until 14 days after last dose (approximately 43 days after first dose of study drug)

• PK: Maximum Observed Drug Concentration (Cmax) of LY3471851 After First and Last Dose

  Baseline until last study visit (approximately 79 days after first dose of study drug)

• PK: Time to Maximum Plasma Concentration (Tmax) of LY3471851

  Baseline until last study visit (approximately 79 days after first dose of study drug)

• PK: Time to Decrease in Concentration of LY3471851 by Half (T1/2) Due to Elimination

  Baseline until last study visit (approximately 79 days after first dose of study drug)

• Pharmacodynamics (PD): Measurement of Change in Number of Regulatory T Cells (Tregs) and Subsets of Tregs in Blood

  Baseline until last study visit (approximately 79 days after first dose of study drug)

Study Arms (4)

Cohort 1 - 3 μg/kg LY3471851

EXPERIMENTAL

Participants received 3 microgram per kilogram (μg/kg) of LY3471851 or placebo on days 1, 15 and 29 by subcutaneous (SC) injection.

Drug: LY3471851; Drug: Placebo

Cohort 1 - 6 μg/kg LY3471851

EXPERIMENTAL

Participants received 6 μg/kg of LY3471851 or placebo on days 1, 15 and 29 by SC injection.

Drug: LY3471851; Drug: Placebo

Cohort 1 - 12 μg/kg LY3471851

EXPERIMENTAL

Participants received 12 μg/kg of LY3471851 or placebo on days 1, 15 and 29 by SC injection.

Drug: LY3471851; Drug: Placebo

Cohort 1 - 24 μg/kg LY3471851

EXPERIMENTAL

Participants received 24 μg/kg of LY3471851 or placebo on days 1, 15 and 29 by SC injection.

Drug: LY3471851; Drug: Placebo

Interventions

LY3471851 DRUG

LY3471851 drug product is a sterile liquid for subcutaneous injection that will be diluted with sterile 0.9% sodium chloride solution for injection (USP) prior to administration.

Also known as: NKTR-358

Cohort 1 - 12 μg/kg LY3471851; Cohort 1 - 24 μg/kg LY3471851; Cohort 1 - 3 μg/kg LY3471851; Cohort 1 - 6 μg/kg LY3471851

Placebo DRUG

The placebo dosing solution is 0.9% sodium chloride for injection (USP).

Cohort 1 - 12 μg/kg LY3471851; Cohort 1 - 24 μg/kg LY3471851; Cohort 1 - 3 μg/kg LY3471851; Cohort 1 - 6 μg/kg LY3471851

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give written informed consent and comply with study procedures and requirements.
• Body mass index (BMI) between 18.0 and 32.0 kilograms per square meter (kg/m²).
• Systolic blood pressure between 90 to 140 millimeters of mercury (mm Hg), diastolic blood pressure between 50 to 90 mm Hg, and resting heart rate between 40 to 100 beats per minute.
• Diagnosis of adult SLE according to the 1997 ACR classification criteria for at least 6 months prior to signing the informed consent form (ICF).
• Minimal to moderate SLE disease activity (active SLE clinical disease is not required for enrollment into the study and participants with severe SLE clinical disease activity, based on the evaluation of the investigator, should be excluded).
• If a participant is taking oral prednisone (or prednisone equivalent) for their SLE, the dose must be less than or equal to (≤) 10 milligrams per day (mg/day) for a minimum of 8 weeks prior to screening. In addition, the dose of oral prednisone or prednisone equivalent the participant is taking must be stable for a minimum of 2 weeks prior to screening.
• If a participant is taking any of the medications below for their SLE, the medication must have been administered for a minimum of 12 weeks prior to signing the ICF, and at a stable dose for a minimum of 8 weeks prior to signing the ICF:
• Azathioprine ≤ 200 mg/day
• Antimalarial (e.g., chloroquine, hydroxychloroquine, quinacrine)
• Mycophenolate mofetil ≤ 2 grams per day (g/day) or mycophenolic acid ≤ 1.44 g/day
• Oral, SC, or intramuscular methotrexate ≤ 15 milligrams per week (mg/week).
• Willing and able to participate in the study for a duration of up to 4 months.
• Willing and able to abstain from participating in another clinical study for a duration of up to 4 months.
• Female participants will be non-pregnant, non-lactating, and either postmenopausal for at least 2 years, or surgically sterile for at least 3 months, or will agree to use double barrier contraception from period prior to study enrollment until 5 months following the last dose received; women of child-bearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test at screening and randomization prior to administration of investigational product.
• Male participants with female partners of childbearing potential must agree to use double barrier contraception during the study (until 5 months following the last dose received). Sperm donation is also restricted during the time-frame that males must be using double barrier contraception. This criterion may be waived for male participants who have had a vasectomy greater than (\>) 6 months prior to enrollment.

You may not qualify if:

• Medical Conditions:
• Current active bacterial, viral, or fungal infection.
• Evidence of significant hematologic dysfunction.
• Evidence of significant liver or kidney dysfunction.
• History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome.
• Active severe or unstable neuropsychiatric SLE.
• Active severe SLE-driven renal disease or history of severe active lupus nephritis with persisting proteinuria levels greater than 0.5 grams/24 hours.
• Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE.
• History of, or current, inflammatory joint or skin disease other than SLE.
• History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than 2 weeks within the last 24 weeks prior to signing the ICF.
• Active tuberculosis (TB) on the basis of positive medical history or chest radiograph (OR) evidence of latent TB or by positive (or persistently indeterminate) Quantiferon-TB Gold or T-Spot test.
• Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection.
• Confirmed positive serology for hepatitis B, hepatitis C (Viral Hepatitis C Antibody Screen \[anti-HCV\]), or a positive result for human immunodeficiency virus (HIV) antibody screen.
• Any severe herpes infection at any time prior to screening per judgement of the investigator.
• History of opportunistic infection requiring hospitalization or intravenous antimicrobial treatment within 3 years prior to randomization.

Sponsors & Collaborators

• Nektar Therapeutics: lead
• Eli Lilly and Company: collaborator

Study Sites (14)

Investigator Site - Anniston

Anniston, Alabama, 36207, United States

Location

Investigator Site - La Jolla

La Jolla, California, 92037, United States

Location

Investigator Site - Clearwater

Clearwater, Florida, 33765, United States

Location

Investigator Site - Orlando

Orlando, Florida, 32806, United States

Location

Investigator Site-Tampa

Tampa, Florida, 33603, United States

Location

Investigator Site - Great Neck

Great Neck, New York, 11021, United States

Location

Investigator Site- Wilmington

Wilmington, North Carolina, 28401, United States

Location

Investigator Site - Middleburg Heights

Middleburg Heights, Ohio, 44130, United States

Location

Investigator Site - Duncansville

Duncansville, Pennsylvania, 16635, United States

Location

Investigator Site - Jackson

Jackson, Tennessee, 38305, United States

Location

Investigator Site - Memphis

Memphis, Tennessee, 38119, United States

Location

Investigator Site - Austin

Austin, Texas, 78745, United States

Location

Investigator Site - Dallas

Dallas, Texas, 75231, United States

Location

Investigator Site - Mesquite

Mesquite, Texas, 75150, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2018
• First Posted: June 14, 2018
• Study Start: April 18, 2018
• Primary Completion: August 29, 2019
• Study Completion: August 29, 2019
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)