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

• Register: ClinicalTrials.gov
• Last refreshed on: 27 November 2023
• Main ID: NCT03556007
• Date of registration: 07/05/2018
• Prospective Registration: No
• Primary sponsor: Nektar Therapeutics
• Public title: A Study of NKTR-358 (LY3471851) in Participants With Systemic Lupus Erythematosus (SLE)
• Scientific title: A Phase 1, Double-blind, Randomized, Placebo-controlled, Ascending Multiple-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous NKTR-358 in Patients With Systemic Lupus Erythematosus
• Date of first enrolment: April 18, 2018
• Target sample size: 48
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03556007
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Study Director
• Affiliation: Nektar Therapeutics

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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 (ß-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.

Exclusion Criteria:

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.

- History of major surgery within 12 weeks of screening or will require major surgery
during the study.

- Clinically significant electrocardiographic abnormalities.

- History of any significant cardiovascular disease (e.g., myocardial infarction,
congestive heart failure, uncontrolled hypertension, cerebrovascular accident),
thrombotic episode, or any severe non-SLE medical illness within the previous 1 year.

- History of cancer, apart from:

- Squamous or basal cell carcinoma of the skin that has been successfully treated.

- Cervical cancer in situ that has been successfully treated.

Medications:

- Receipt of any investigational product (small molecule or biologic agent) within 4
weeks or 5 half-lives prior to signing of the ICF, whichever is greater.

- Receipt of belimumab in 6 months prior to screening.

- History of treatment with rituximab or ocrelizumab (or other B cell depleting agent)
within 6 months prior to screening. For participants who received their last treatment
with rituximab or ocrelizumab more than 6 months earlier, evidence of significant and
persisting low B cell levels in blood.

- History of cytotoxic medications (e.g., cyclophosphamide) within preceding 12 months.

- Receipt of any intra-articular, intramuscular, or intravenous (IV) glucocorticoids
within 6 weeks prior to screening.

- Receipt of blood products within 6 months prior to screening.

General:

- Receipt of blood products within 6 months prior to screening and donation of blood or
plasma to a blood bank or for a clinical study (except for screening of this study)
within 28 days prior to screening.

- Participants who have a history of organ or bone marrow transplant.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: LY3471851

Drug: Placebo

Primary Outcome(s)

Safety and Tolerability of LY3471851 - Number of Participants Experiencing Adverse Events [Time Frame: Informed consent until last study visit (approximately 79 days after first dose of study drug)]

Secondary Outcome(s)

PD: Measurement of Cytokines in Blood [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (Joint Score): Evaluation of Swollen Joints in the Body [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI): Physical Examination [Time Frame: 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 [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (SLEDAI): Blood: Measurement of Anti-dsDNA, Complement, White Blood Cells and Platelets [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI): Blood Analysis [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI): Urine Analysis [Time Frame: 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 [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

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 [Time Frame: Baseline until 14 days after last dose (approximately 43 days after first dose of study drug)]

Change in Disease Activity (Cutaneous Lupus Erythematosus Disease Area Severity Index (CLASI): Evaluation of Mucous Membrane [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (Cutaneous Lupus Erythematosus Disease Area Severity Index (CLASI): Evaluation of Scalp [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (Cutaneous Lupus Erythematosus Disease Area Severity Index (CLASI): Evaluation of Hair Loss [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

PD: Measurement Activity of Tregs [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (SLEDAI): Urine; Measurement of Hematuria, Pyuria, Urinary Casts, Creatinine, Protein [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

PD: Measurement of Change in Number of Subsets of Conventional T Cells (Tcons) in Blood [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

PK: Maximum Observed Drug Concentration (Cmax) of LY3471851 After First and Last Dose [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (Cutaneous Lupus Erythematosus Disease Area Severity Index (CLASI): Evaluation of Skin on the Body [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Change in Disease Activity (Joint score): Evaluation of Tender Joints in the Body [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

PD: Measurement of Change in Number of Natural Killer Cells (NK Cells) in Blood [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

PK: Time to Maximum Plasma Concentration (Tmax) of LY3471851 [Time Frame: Baseline until last study visit (approximately 79 days after first dose of study drug)]

Secondary ID(s)

J1P-MC-KFAB

17-358-02

17238

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Eli Lilly and Company