The purpose of this study is to learn about the effects, safety and how PF-06823859 is processed in adults with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) showing some skin symptoms. This study is seeking for participants who: * are adults of 18 years of age or older. * are confirmed to have CLE or SLE with involvement of the skin. * have a Cutaneous Lupus Erythematosus Disease Area and Severity Index activity (CLASI-A) score of at least 8. About 48 participants will be selected to receive active study medicine (PF-06823859) or placebo (an infusion without drug). About 32 are grouped to receive the active study medicine and 16 are to receive placebo. They will be receiving the treatments by intravenous infusion (injected directly into the veins). At week 16 all participants receiving the active study drug since day 1 and participants who have received placebo since day 1 and are not responding clinically will receive active study medication. Patients who have received placebo since Day 1 and who have had a clinical response will continue to receive placebo till week 40. All participants will have last follow-up visit at Week 60. The study will compare participants receiving PF-06823859 to participants who receive placebo. This will help us see if PF-06823859 is safe and effective to treat CLE or SLE with skin symptoms and improve participant's CLASI-A score. Participants will take part in this study for about 65 weeks. This includes up to a 5-week selection period, a 12-week Q4Wk treatment period, a 36-week Q8Wk treatment period, and a 12-week follow-up period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
8
Placebo (intravenous infusion)
PF-06823859 (intravenous infusion)
The Kirklin Clinic of UAB Hospital
Birmingham, Alabama, United States
University of Alabama at Birmingham - School of Medicine
Birmingham, Alabama, United States
University of Alabama at Birmingham, Department of Dermatology
Birmingham, Alabama, United States
The University of Alabama at Birmingham
Birmingham, Alabama, United States
Mayo Clinic Hospital
Phoenix, Arizona, United States
Mayo Clinic in Arizona - Scottsdale
Scottsdale, Arizona, United States
Dermatology Research Associates
Los Angeles, California, United States
Emory University
Atlanta, Georgia, United States
The University of Kansas Hospital
Kansas City, Kansas, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
...and 9 more locations
Change From Baseline in Type 1 Interferon (IFN) Gene Signature (GS) Score in Lesional Skin at Week 12
Change from baseline GS was calculated as GS(t) - GS(0), where GS(t) was the gene signature score at Week 12 and GS(0) was the gene signature score at Baseline, where the GS(t) was calculated as the mean of log2 transformed counts per million reads from each of 13 genes in RNAseq, the higher GS indicated coordinated higher expression. There is no minimum/maximum limit to the GS score. Gene expression was quantified using RNA sequencing and summarized as log2-transformed counts per million mapped reads \[log2(CPM)\]. Higher values indicate higher normalized gene expression and without a bounded scale or defined minimum or maximum value.
Time frame: Baseline, Week 12
Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) Score at Week 12
CLASI-A measures erythema and scaling or hypertrophy in thirteen skin regions. CLASI-A scores ranges from 0 to 70, with higher scores indicating more severe skin disease.
Time frame: Baseline, Week 12
Percent Change From Baseline in CLASI-A Score at Weeks 4, 8, 16, 20, 24, 32, 40, 48 and 60
CLASI-A measures erythema and scaling or hypertrophy in thirteen skin regions. CLASI-A scores ranges from 0 to 70, with higher scores indicating more severe skin disease. Participants receiving PF-06823859 continued Q4W then Q8W treatment, while both participants receiving placebo switched to PF-06823859 at Week 16. Results are reported by treatment sequence to reflect protocol pathways and maintained the initial randomized comparison.
Time frame: Baseline, Weeks 4, 8, 16, 20, 24, 32, 40, 48 and 60
Change From Baseline in CLASI-A Score at Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
CLASI-A measures erythema and scaling or hypertrophy in thirteen skin regions. CLASI-A scores ranges from 0 to 70, with higher scores indicating more severe skin disease. Participants receiving PF-06823859 continued Q4W then Q8W treatment, while both participants receiving placebo switched to PF-06823859 at Week 16. Results are reported by treatment sequence to reflect protocol pathways and maintained the initial randomized comparison.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
Percentage of Participants With Greater Than or Equal to (>=) 50 Percent Reduction in CLASI-A Score at Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
CLASI-A measures erythema and scaling or hypertrophy in thirteen skin regions. CLASI-A scores ranges from 0 to 70, with higher scores indicating more severe skin disease. Percentage of participants with \>=50 percent reduction in CLASI-A score at the specified timepoints was reported in this outcome measure. Participants receiving PF-06823859 continued Q4W then Q8W treatment, while both participants receiving placebo switched to PF-06823859 at Week 16. Results are reported by treatment sequence to reflect protocol pathways and maintained the initial randomized comparison.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
Percentage of Participants With >=4 Points Reduction in CLASI-A Score at Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
CLASI-A measures erythema and scaling or hypertrophy in thirteen skin regions. CLASI-A scores ranges from 0 to 70, with higher scores indicating more severe skin disease. Percentage of participants with \>=4 points reduction in CLASI-A score at the specified timepoints was reported in this outcome measure. Participants receiving PF-06823859 continued Q4W then Q8W treatment, while both participants receiving placebo switched to PF-06823859 at Week 16. Results are reported by treatment sequence to reflect protocol pathways and maintained the initial randomized comparison.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
Percentage of Participants With >=7 Points Reduction in CLASI-A Score at Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
CLASI-A measures erythema and scaling or hypertrophy in thirteen skin regions. CLASI-A scores ranges from 0 to 70, with higher scores indicating more severe skin disease. Percentage of participants with \>=7 points reduction in CLASI-A score at the specified timepoints was reported in this outcome measure. Participants receiving PF-06823859 continued Q4W then Q8W treatment, while both participants receiving placebo switched to PF-06823859 at Week 16. Results are reported by treatment sequence to reflect protocol pathways and maintained the initial randomized comparison.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
Change From Baseline in Physician Global Assessment (PhGA) Score at Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
PhGA score was assigned by physician as the number within the 0 to 100 millimeter range on visual assessment scale and provided a global characterization of disease. Higher scores indicating more severe disease. Participants receiving PF-06823859 continued Q4W then Q8W treatment, while both participants receiving placebo switched to PF-06823859 at Week 16. Results are reported by treatment sequence to reflect protocol pathways and maintained the initial randomized comparison.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60
Number of Participants With Laboratory Test Abnormalities of Grade 3 or More According to Common Terminology Criteria for Adverse Events (CTCAE) Version (v) 5.0
Laboratory test included activated partial thromboplastin time prolonged, alanine aminotransferase increased, alkaline phosphatase increased, anemia, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase (CPK) increased, cholesterol high, creatinine increased, hemoglobin increased, hypercalcemia, hyperkalemia, hypernatremia, hypertriglyceridemia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, international normalized ratio (INR) increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased. Laboratory test abnormalities were graded according to CTCAE v5.0; grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Participants with any laboratory abnormalities of CTCAE v5.0 grade 3 or more were reported in this outcome measure.
Time frame: For Q4W arms: Day 1 up to pre-dose of Week 16; for Q8W arms: from dosing of Week 16 to Week 60
Number of Participants With Clinically Significant Vital Signs Abnormalities
Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR). Clinically significant vital signs abnormalities were based on investigator's decision.
Time frame: For Q4W arms: Day 1 up to pre-dose of Week 16; for Q8W arms: from dosing of Week 16 to Week 60
Number of Participants With Clinically Significant Electrocardiogram (ECG) Results
ECG parameters included PR interval, QRS duration and QT interval using Fridericia's formula (QTcF) interval. Clinically significant abnormalities in ECG parameters were based on investigator's decision.
Time frame: For Q4W arms: Day 1 up to pre-dose of Week 16; for Q8W arms: from dosing of Week 16 to Week 60
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Who Discontinued Study Due to TEAEs
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were the AEs with onset dates on or after the start of the study intervention up to after last dose of study intervention. An serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or any other pre-specified criteria in protocol of the study or other important medical events. AEs included SAEs (if occurred) and all other AEs (including non-SAEs).
Time frame: For Q4W arms: Day 1 up to pre-dose of Week 16; for Q8W arms: from dosing of Week 16 to Week 60
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