Lupus Erythematosus, Systemic, Lupus Erythematosus, Cutaneous
Conditions
Keywords
type 1 IFN gene signature, SLE, CLE
Brief summary
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.
Interventions
DRUGPlacebo
Placebo (intravenous infusion)
DRUGPF-06823859
PF-06823859 (intravenous infusion)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
About 48 eligible participants will be randomized in a 2:1 ratio to receive either PF-06823859 or placebo. Following assessments for the primary endpoint at Week 12, participants who are receiving active PF-06823859 or who are placebo non responders (responder is defined by ≥4 point reduction from the baseline in CLASI-A score) will receive PF-06823859 beginning at Week 16, while placebo responders will continue to be in the placebo group. The last dose of study intervention will be administered at Week 40 followed by last full study assessments at Week 48. The final follow up visit will be conducted at Week 60.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Have a histologically confirmed active CLE or SLE with cutaneous manifestations in the form of subacute cutaneous lupus erythematosus or/and discoid/chronic cutaneous lupus erythematosus at least 3 months and CLASI-A at least 8 or higher. * Participant has adequate intravenous infusion access per investigator's judgement * Willing to comply with study procedures including skin punch biopsies procedures. * Weight is greater than 40 kg and less than 130 kg.
Exclusion criteria
* Skin disorders other than CLE or SLE. * Active, severe lupus nephritis requiring treatment with cytotoxic agents or high-dose steroids. * Active severe central nervous system lupus requiring therapeutic intervention within 60 days of baseline. * Cancer or a history of cancer within 5 years of screening except adequately resected basal or squamous cell carcinoma of the skin, or carcinoma in situ of uterine cervix. * Known history of a major cardiovascular or cerebrovascular event within 24 months, pulmonary arterial hypertension, pulmonary embolism within 6 months of screening. * Have any autoimmune or inflammatory disease that would interfere with interpretation of test results or clinical assessments. * History of disseminated herpes zoster/simplex or recurrent herpes zoster. * Serious infection within 60 days of baseline or an active infection treated with oral antibiotics within 14 days of baseline. * Have evidence of active or latent infection of hepatitis B or C, known history of human immunodeficient virus (HIV) infection, or infected with Mycobacterium TB (active or latent TB) * Laboratory abnormalities that meet
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Type 1 Interferon (IFN) Gene Signature (GS) Score in Lesional Skin at Week 12 | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) Score at Week 12 | Baseline, 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. |
| Percent Change From Baseline in CLASI-A Score at Weeks 4, 8, 16, 20, 24, 32, 40, 48 and 60 | Baseline, 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. |
| Change From Baseline in CLASI-A Score at Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60 | Baseline, 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. |
| 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 | 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. |
| Percentage of Participants With >=4 Points Reduction in CLASI-A Score at Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60 | 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. |
| Percentage of Participants With >=7 Points Reduction in CLASI-A Score at Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60 | 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. |
| Change From Baseline in Physician Global Assessment (PhGA) Score at Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 60 | Baseline, 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. |
| 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 | For Q4W arms: Day 1 up to pre-dose of Week 16; for Q8W arms: from dosing of Week 16 to Week 60 | 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. |
| Number of Participants With Clinically Significant Vital Signs Abnormalities | For Q4W arms: Day 1 up to pre-dose of Week 16; for Q8W arms: from dosing of Week 16 to Week 60 | 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. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Results | For Q4W arms: Day 1 up to pre-dose of Week 16; for Q8W arms: from dosing of Week 16 to Week 60 | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Who Discontinued Study Due to TEAEs | For Q4W arms: Day 1 up to pre-dose of Week 16; for Q8W arms: from dosing of Week 16 to Week 60 | 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). |
Countries
Canada, Greece, Spain, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
Initially participants were randomized to receive PF-06823859 or placebo in Period 1. In Period 2, participants in PF-06823859 group continued to receive the same, while participants who received placebo, depending upon the response, either continued receiving placebo (if responded to treatment) or were administered with PF-06823859 (non-responders). No participants continued to receive placebo in Period 2.
Pre-assignment details
As per Sponsor's decision, dose strength of PF-06823859 is not disclosed and is designated as "Dose A" in every section of the record. The study was terminated due to sponsor decision and was not due to safety concerns or clinical effect reasons or request from any regulatory authorities.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 49.83 Years STANDARD_DEVIATION 7.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 4 / 6 | 4 / 6 | 1 / 2 | 1 / 2 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 2 |
Outcome results
None listed