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
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Pfizer
- Enrollment
- 8
- Locations
- 31
- Primary Endpoint
- Change From Baseline in Type 1 Interferon (IFN) Gene Signature (GS) Score in Lesional Skin at Week 12
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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 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.
Arms & Interventions
Group 2
Placebo
Intervention: Placebo (Drug)
Group 1
PF-06823859
Intervention: PF-06823859 (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Type 1 Interferon (IFN) Gene Signature (GS) Score in Lesional Skin at Week 12
Time Frame: 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 Outcomes
- Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) Score at Week 12(Baseline, Week 12)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)