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-PL
- 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. If receiving antimalarials in combination with corticosteroids, the minimum dose of corticosteroids permitted as part of this combination is 5 mg prednisone daily or an equivalent dose and steroids must have been started at least 8 weeks prior to Day 1. 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, however brief fluctuations in therapy for toxicity are permitted (eg, holding a dose (=7 days) or temporary reduction in corticosteroids of less than 3 mg/day. See Appendix 13 for allowable stable doses.
Have active disease defined as:
SLEDAI-2K score of =8 points at screening and at randomization and Clinical SLEDAI-2K score of =6 points at both screening and at randomization.
NOTE: Clinical SLEDAI-2K score (See Appendix 11) the SLEDAI-2K score without the inclusion of points attributable to any urine or laboratory results including immunologic measures (a For inclusion in the study, the Clinical SLEDAI-2K calculation for entry will exclude points for: 1.Lupus Headache b) Skin disease involving Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Erythema scores <2, c) Arthritis scores must involve a minimum of 3 joints both swollen and tender, d) .Mucosal ulcers which may have occurred within the previous 30 days but are not noted on exam and CLASI at the time of screening. b.On the day of randomization, a minimum of 3 joints that are both swollen and tender is required if SLEDAI Arthritis is marked PRESENT. The site should check the joint exam prior to randomization to ensure there are =3 joints that are both tender and swollen to avoid a protocol deviation. c.For SCREENING and ONSTUDY
• Active, severe lupus nephritis (World Health Organization Class III, IV) that requires or may require treatment with cytotoxic agents or high-dose CS are excluded. Participants with prior, controlled, renal disease that has been treated with an ACE or ARB inhibitor and immunosuppressive therapy (cyclophosphamide or mycophenolate mofetil) with serum creatinine = 2× upper limit of normal (ULN) and either residual proteinuria up to =3 g/day or a urine protein/creatinine ratio (UPCR) of =3 mg/mg or339 mg/mmol are allowed if prior treatment has been demonstrated. Control of renal disease must be documented with at least 2 measurements of proteinuria or UPCR over the past 6 months. Participants with pure Type V membranous nephropathy must be biopsy confirmed if immunosuppressive therapy was not administered. Pfizer clinical and adjudicators will make the final decision regarding this exclusion criteria. If at all possible, biopsy results confirming the diagnosis should be available in the participant chart.
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, active 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 within 5 years of screening (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 considered to be treated and cured, a note from the oncologist, or specialist following the participant for recurrence noting they are aware of and agree with potential participation should be available in the source document. Potential participants who have an unacceptably high risk of tumor recurrence may be rejected by the Sponsor or their delegate. 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 an 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 participant 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 part
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