A Study to Learn About the Study Medicine (PF-06823859) in Adults With Active CLE or SLE With Skin Symptoms.

Study Overview
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Brief Summary
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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 some symptoms of the skin. have a cutaneous LE disease area and severity index activity (CLASI-A) score 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, participants receiving the active study medicine and non-clinical responders from placebo will receive the active study medicine. The placebo clinical responders 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 and improve the 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 start of treatment period, a 36-week long term extension treatment period, and a 12-week follow-up period.

Official Title
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A PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE CLINICAL EFFECT, PHARMACODYNAMIC, PHARMACOKINETIC AND SAFETY PROFILE OF PF-06823859 IN ADULT PARTICIPANTS WITH ACTIVE CLE OR SLE WITH CUTANEOUS MANIFESTATIONS

Conditions
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Lupus Erythematosus, Systemic, Lupus Erythematosus, Cutaneous

Intervention / Treatment
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* Drug: Placebo
* Drug: PF-06823859


Participation Criteria
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Eligibility Criteria
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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 study procedures including skin punch biopsies procedures. Weight is greater than 40 kg and less than130 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 cutaneous basal cells, squamous cell carcinoma, or carcinoma in situ of uterine cervix. Known history of a major cardiovascular or cerebrovascular event, pulmonary arterial hypertension, pulmonary embolism within 6 months Have any autoimmune or inflammatory disease that would interfere with interpretation of test results or clinical assessments. History of disseminated herpes zoster or disseminated herpes simplex or recurrent localized, dermatomal herpes zoster. Serious infection within 60 days of baseline or an active infection treated with oral anti-biotics 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 without adequately treatment Laboratory abnormalities meet exclusion criteria at the Screening visit. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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 follow up visit will be conducted at Week 60.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>PF-06823859 | Drug: PF-06823859<br>* PF-06823859 (intravenous infusion)<br>|
| Placebo Comparator: Group 2<br>Placebo | Drug: Placebo<br>* Placebo (intravenous infusion)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in type 1 IFN GS score in lesional skin at Week 12 | A 13-gene IFN gene signature score was used to measure IFN activity at both baseline and week 12, the gene signature score is assessed per sample by averaging the log2CPM(Counts Per Million reads) values of these 13 genes through RNAseq profiling. The gene signature score is positively linked to the gene expression activity of those 13 genes that are related to IFN. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in CLASI-A score at Week 12 | The Cutaneous Erythematosus Disease Area and Severity Index (CLASI) is a clinician rated scale composed of 56 items designed to assess the disease activity and damage in CLE in adults. The disease activity (CLASI-A) sub-score ranges from 0 to 70: 0-9 indicating mild disease, 10-20 indicating moderate disease, and 21-70 indicating severe disease. | Week 12 | 
| Percent change from baseline in CLASI-A (over time in addition to Week 12) | Percent Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score to Week 4 and Week 8 | Week 4 and Week 8 | 
| Change from baseline in CLASI-A score at Week 12 | Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score to Week 4, 8 and 12 | Week 4, 8, and 12 | 
| Achieving ≥50%, 4 or 7 points reduction in CLASI-A (over time) | Achieving ≥50%, 4 or 7 points reduction in CLASI-A at Week 4, 8 and 12 | Week 4, 8, 12 | 
| Change from baseline in Physician global assessment (PhGA) (over time) | The PhGA is a visual analog scale (VAS) tool to measure worsening in the participant general health status. Physician will place a mark on the scale between 0 (none), 1 (mild), 2(moderate) and 3 (severe). | Week 4, 8 and 12 | 
| Incidence and severity of laboratory, vital signs, 12-lead ECG abnormalities, AEs, SAEs and withdrawals due to AEs over time |  | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 1 IFN gene signature