Assessment of PF-06700841 in participants with moderate to severe active, generalized Systemic Lupus Erythematosus (SLE) that have inadequate response to standard of care.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
350
Percentage of Participants Achieving SLE Responder Index (SRI) Change of 4 (SRI-4) at Week 52
SRI-4 components included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG) 2004 and Physician's Global Assessment (PhGA). Participants were classified as SRI-4 responders, if they met all of the following criteria compared with baseline: 1) greater than or equal to (\>=) 4 point reduction in SLEDAI-2K score; 2) no new BILAG A organ domain score or 2 new BILAG B organ domain scores; 3) no worsening (less than \[\<\] 0.3 point increase) in PhGA score. SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG: assesses disease extent, severity in individual organ system (range: A \[severe\] to E \[no disease\]; higher score = less severity). PhGA: assesses worsening in participant's general health status (range: 0 \[none\] to 3 \[severe\]; higher score = higher severity).
Time frame: Week 52
Percentage of Participants Achieving British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) at Week 52
BICLA included: BILAG-2004, SLEDAI-2K and PhGA. Participants were classified as responders, if they met all the following criteria: BILAG-2004 improvement (all A scores at baseline improved to B/C/D and all B scores improved to C or D); no worsening in disease activity (no new BILAG-2004 A scores or =\<1 new B score); no worsening of total SLEDAI-2K score; no significant deterioration (\<10 percent \[%\] worsening) in analogue PhGA. SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG: assesses disease extent, severity in individual organ system (range: A \[severe\] to E \[no disease\]; higher score = less severity). PhGA: assesses worsening in participant's general health status (range: 0 \[none\] to 3 \[severe\]; higher score = higher severity).
Time frame: Week 52
Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 52
LLDAS was defined as SLE disease activity index (SLEDAI-2k \<=4, with no activity in major organ systems \[renal, central nervous system, cardiopulmonary, vasculitis, fever\]) and no haemolytic anaemia or gastrointestinal activity; no new lupus disease activity compared with the previous assessment; a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI PhGA (scale 0-3; higher scores = higher severity) \<=1; a current prednisolone (or equivalent) dose \<=7.5 milligram per day (mg/daily); and well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.
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PF-06700841 45 mg
UAB Department of Medicine Clinical Research Enterprise
Birmingham, Alabama, United States
The Kirklin Clinic
Birmingham, Alabama, United States
UAB Hospital Department of Pharmacy
Birmingham, Alabama, United States
UAB Hospital-Clinical Research Unit (CRU)
Birmingham, Alabama, United States
The University of Alabama at Birmingham
Birmingham, Alabama, United States
UAB Department of Medicine Clinical Research Enterprise
Birmingham, Alabama, United States
St. Joseph Heritage Healthcare
Fullerton, California, United States
Advanced Medical Research, LLC
La Palma, California, United States
Arthritis and Osteoporosis Medical Center
La Palma, California, United States
Desert Medical Advances
Palm Desert, California, United States
...and 154 more locations
Time frame: Week 52
Percentage of Participants Achieving a Reduction in Prednisone (or Equivalent) Dose to <=7.5 mg/Day and Sustained for 12 Weeks Prior to Week 52 in Participants on Prednisone >7.5 mg/Day (or Equivalent) at Baseline
In this outcome measure data is reported for participants who achieved a reduction in prednisone (or equivalent) dose to \<=7.5 mg/day and sustained for 12 Weeks prior at Week 52 and they also sustained this dose reduction for 12 weeks prior to Week 52 (Week 40 to Week 52).
Time frame: Week 52 for achieving reduction in dose along with Week 40 to Week 52 for sustained dosing
Percentage of Participants Achieving a SRI-4 Response With Prednisone Dose Reduced to <=7.5 mg/Day and Sustained for 12 Weeks at Week 52 in Participants on Prednisone >7.5 mg/Day (or Equivalent) at Baseline
In this outcome measure data is reported for participants who achieved a reduction in SRI-4 response with prednisone dose reduced to \<=7.5 mg/day and sustained for 12 weeks at Week 52.
Time frame: 12 Weeks prior at Week 52 (Week 40 to Week 52)
Percentage of Participants With >= 50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 52 in Participants With Baseline CLASI-A Score >=10
CLASI is an validated measurement instrument for lupus erythematosus developed for use in clinical studies that consists of separate scores for the activity of the disease (CLASI-A). The CLASI activity score is calculated on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI activity score ranges from 0-70, with higher scores indicating more severe skin disease. Severity categories based on the CLASI activity score are as follows: mild (0-9), moderate (10-20), and severe (21-70).
Time frame: Week 52
Change From Baseline in Total Scores of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 52
The FACIT-F Scale is a participant completed questionnaire consisting of 13 items that assess fatigue. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0 = not at all; 1 = a little bit; 2 =somewhat; 3 = quite a bit; 4 = very much). Instrument scoring yielded a range from 0 to 52 (negatively worded items were reversed during analysis), with higher scores representing better participant status (less fatigue).
Time frame: Baseline, Week 52
Change From Baseline in Physical Health Domain Scores of Lupus Quality of Life (LupusQoL) at Week 52
The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others; measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Physical health domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.
Time frame: Baseline, Week 52
Change From Baseline in Emotional Health Domain Scores of LupusQoL at Week 52
The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Emotional health domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.
Time frame: Baseline, Week 52
Change From Baseline in Body Image Domain Scores of LupusQoL at Week 52
The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Body image domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.
Time frame: Baseline, Week 52
Change From Baseline in Pain Domain Scores of LupusQoL at Week 52
The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Pain domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.
Time frame: Baseline, Week 52
Change From Baseline in Planning Domain Scores of LupusQoL at Week 52
The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Planning domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.
Time frame: Baseline, Week 52
Change From Baseline in Fatigue Domain Scores of LupusQoL at Week 52
The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Fatigue domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.
Time frame: Baseline, Week 52
Change From Baseline in Intimate Relationship Domain Scores of LupusQoL at Week 52
The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Intimate relationship domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.
Time frame: Baseline, Week 52
Change From Baseline in Burden to Others Domain Scores of LupusQoL at Week 52
The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Burden to others domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.
Time frame: Baseline, Week 52
Incidence Rate of Severe Flare Event
Incidence rate was defined as the number of new events per 100 person-years.
Time frame: Week 52
Number of Participants With Treatment-Emergent Adverse Events (AE)
An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are events from first dose of study intervention to 4 weeks after last dose of study intervention that were absent before treatment or that worsened relative to pre-treatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and all non-SAEs.
Time frame: Day 1 of dosing up to 4 weeks after last dose of study drug (maximum treatment was up to 52 weeks, follow-up up to 56 weeks)
Number of Participants With Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Day 1 of dosing up to 4 weeks after last dose of study drug (maximum treatment was up to 52 weeks, follow-up up to 56 weeks)
Number of Participants With Adverse Events Leading to Discontinuation From Study
An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. In this outcome measure, participants with adverse events leading to discontinuation from study were reported.
Time frame: Day 1 of dosing up to 4 weeks after last dose of study drug (maximum treatment was up to 52 weeks, follow-up up to 56 weeks)
Number of Participants With Clinically Significant Vital Signs Abnormalities
Vital signs included blood pressure, pulse rate, respiratory rate, and temperature. Clinical significance in vital signs abnormalities was judged by investigator.
Time frame: Day 1 of dosing up to 4 weeks after last dose of study drug (maximum treatment was up to 52 weeks, follow-up up to 56 weeks)
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Clinical significance in ECG abnormalities was judged by investigator.
Time frame: Day 1 of dosing up to 4 weeks after last dose of study drug (maximum treatment was up to 52 weeks, follow-up up to 56 weeks)
Number of Participants With Laboratory Test Abnormalities
Hematology (Hemoglobin\[hgb\], hematocrit, erythrocytes\[ery\]:\<0.8\*lower limit of normal\[LLN\];reticulocytes, reticulocytes/ery:\<0.5\*LLN,\>1.5\*upper LN\[ULN\];ery mean corpuscular volume\[EMC\], EMC hgb:\<0.9\*LLN,\>1.5\*ULN;EMC hgb concentration:\<0.9\* LLN;platelet:\<0.5\*LLN;leukocytes\[leu\]:\<0.6\*LLN,\>1.5\*ULN;lymphocytes, lymphocytes/leu, neutrophils, neutrophils/leu:\<0.8\* LLN,\>1.2\*ULN;basophils, basophils/leu, eosinophils, eosinophils/leu, monocytes, monocytes/leu:\>1.2\*ULN;activated partial thromboplastin time\[PTT\], PTT, prothrombin time:\>1.1\*ULN);Clinical chemistry (Total/direct/indirect bilirubin, glucose-fasting:\>1.5\*ULN; aspartate aminotransferase\[AT\], alanine AT:\>3.0\*ULN; protein, albumin, HDL cholesterol:\<0.8\*LLN;urea nitrogen, creatinine, triglyceride, cholesterol:\>1.3\*ULN;urate, LDL cholesterol:\>1.2\*ULN;potassium:\<0.9\*LLN,\>1.1\*ULN;calcium, bicarbonate:\<0.9\*LLN;creatine kinase:\>2.0\*ULN);Urinalysis (pH\<4.5;glucose, protein, hgb, ketones, nitrite, leu esterase, granular/hyaline/WBCs casts:\>1).
Time frame: Day 1 of dosing up to 4 weeks after last dose of study drug (maximum treatment was up to 52 weeks, follow-up up to 56 weeks)