A Phase 2b multicenter dose ranging study to evaluate efficacy and safety of PF-06700841 in systemic lupus erythematosus
- Conditions
- Systemic Lupus Erythematosus (SLE)MedDRA version: 21.1Level: PTClassification code 10042945Term: Systemic lupus erythematosusSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2018-004175-12-HU
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 448
• Male or female participants between the ages of 18 (or the minimum country specific age of consent if >18) and 75 years, inclusive, at the time of signing the informed consent document (ICD).
o Refer to Appendix 4 for reproductive and contraceptive criteria for male and female participants.
• Have a clinical diagnosis of SLE according to the 1997 update on the 1982 revised American College of Rheumatology (ACR) Criteria for the Classification of SLE see Appendix 8 OR meet at least 4 of the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria see Appendix 9, including at least 1 clinical criterion and 1 immunologic criterion, at least 6 months prior to dosing of study agent.
• Have serologically positive SLE at the screening visit based on 1 of the following test results from the central laboratory during the screening period:
o ANA titer =1:80, or
o Positive anti dsDNA.
Note: The ANA and/or anti double stranded DNA (anti-dsDNA) measurement may be repeated once at the central laboratory within approximately 2 weeks of the initial value, and the value resulting from repeat testing may be accepted for enrollment eligibility if it meets the eligibility criterion.
• All participants must be currently receiving EITHER a stable dose of an immunosuppressant [methotrexate (MTX), azathioprine(AZA)/6- mercaptopurine (6-MP), leflunomide, mizoribine,
mycophenolate/mycophenolic acid(MMF)] with or without antimalarials and/or corticosteroids, OR anti-malarials (hydroxychloroquine or chloroquine) in combination with corticosteroids. Antimalarial or steroid monontherapy is not permitted. Participants may not be receiving combinations of 2 or more immunosuppressants.
Note: Stable dose is defined as no new therapy or change in standard-of care therapies as above within 12 weeks of Day 1 for immunosuppressives or within 2 weeks of Day 1 for corticosteroids . See Appendix 13 for allowable stable doses. Documented failure must be outlined in the participants medical notes or similar source document.
• Have active disease defined as:
o SLEDAI 2K score of =8 points at screening, and Clinical” SLEDAI 2K score of =6 points at both screening and randomization
NOTE: Clinical SLEDAI 2K score (See Appendix 11) is the SLEDAI 2K score without the inclusion of points attributable to any urine or laboratory results including immunologic measures. For inclusion in the study, the Clinical SLEDAI-2K calculation for entry will exclude points for a) Lupus Headache, b) skin disease involving Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Erythema scores less than 2 and c) arthritis scores must involve a minimum of 3 joints with tenderness, swelling, or effusion (ie rather than 2).
AND
o BILAG Level A disease in =1 organ system (except renal or central nervous system [CNS]) or BILAG B disease in =2 organ systems if no level A disease is present at screening. At least one A or one B level
body system grade must be in the Mucocutaneous or Musculoskeletal systems. A qualifying screening Mucocutaneous B due to BILAG #6, mild skin eruption, must have a CLASI erythema activity score of >=2. A qualifying screening Musculoskeletal B due to #42, moderate arthritis, must show >=3 swollen, tender joints and a qualifying Musculoskeletal A score due to #41, severe arthritis, must show >=6 tender, swollen joints on the screening joint count (see Appendix 12).
Note: Data from the SLICC, SLED
• Have active renal lupus as defined by the following: spot urine protein/creatinine ratio >3.0 mg/mg (proteinuria >3.0 g/24 hours may also be used if available) or have BILAG A renal disease, or have required hemodialysis or active urinary sediment with red blood cell cast(s), or histological evidence (if available) of diffuse proliferative glomerulonephritis within the 12 weeks prior to screening.
o Note: The lab measurements related to lupus nephritis may be repeated once within approximately 2 weeks of the initial values, and the values resulting from repeat testing may be accepted for enrollment eligibility if they meet the eligibility criteria.
• Have severe active central nervous system (CNS) lupus (eg, BILAG A neurological disease and/or active, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia or dementia related to SLE, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis) requiring therapeutic intervention within 60 days of Day 1. Participants with BILAG B level neurologic disease are not excluded as long as they meet all other qualifying criteria for the study.
• Have cancer or a history of cancer (other than adequately resected cutaneous basal cell, squamous cell carcinoma, or carcinoma in situ of the uterine cervix with no evidence of recurrence within the previous 3 years). If a participant is followed for a history of cancer that is consider treated and cured, a note from the oncologist, or specialist following the participant for recurrence should be available in the source document. Additionally, the participant is required to comply with recommended follow up testing with their specialist of record while participating in the
study.
• The following is exclusionary;
- Any history of thrombosis (venous or arterial) or cerebrovascular ischemic event (stroke or transient ischemic attack [TIA]) within the last 6 months.
- A history of a ischemic cerebrovascular event (stroke, TIA) within the past 12 months unless these were caused by known antiphospholipid syndrome and the patients has been adequately anticoagulated (and will continue on anticoagulation per guidelines) according to current guidelines for at least 6 months without a recurrence of any thrombotic event.
- Any history of a pulmonary embolus, unless these were caused by known antiphospholipid syndrome and the patients has been adequately anticoagulated (and will continue on anticoagulation per guidelines) according to current guidelines for at least 6 months without a recurrence of any thrombotic event.
Note. Any participant being treated for antiphospholipid syndrome or anticardiolipin antibodies must be adequately anticoagulated according to current local guidelines. Sites should make every effort to obtain a medical history of at least 3 years duration to document that there have been no thrombotic events or an obstetrical history of repeat fetal losses. In the absence of this medical history information, a hematology consult may be required if antiphospholipid screening tests are positive.
• Active bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, allergic aspergillosis or cavitary lung lesions or granulomatous disease on chest x ray). History of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method