A Phase 2b multicenter dose ranging study to evaluate efficacy and safety of PF-06700841 in systemic lupus erythematosus

Phase 1

• Conditions: Systemic Lupus Erythematosus (SLE); MedDRA version: 21.1Level: PTClassification code 10042945Term: Systemic lupus erythematosusSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2018-004175-12-RO
• Lead Sponsor: Pfizer Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-26
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 448

Inclusion Criteria

• 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 a stable dose of methotrexate (MTX), azathioprine (AZA), leflunomide, mizorbine, mycophenolate/mycophenolic acid (MMF), anti-malarials (hydroxychloroquine or chloroquine) or corticosteroids (if monotherapy, =7.5 mg per day)
Note: Stable dose is defined as no new therapy or change in standard-of-care therapies as above within 12 weeks of Day 1. 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 =6 points at screening, and Clinical” SLEDAI 2K score of =4 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. In addition, 1A and/or 2B BILAG need to be the same clinical disease manifestation(s) at baseline (see Appendix 12).
Note: Data from the SLICC, SLEDAI and BILAG evaluations will be reviewed by the Sponsor and/or the Sponsor-selected independent reviewer(s). For participants to receive their first administration of study agent, approval must be received by the Sponsor and/or Sponsor-selected independent reviewers.

See section 5.1 of the Protocol for a full list of Inclusion Criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 403
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion Criteria

• Have active renal lupus as defined by the following: spot urine protein/creatinine ratio >3.0 mg/g (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. Patients 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).
• Have a history of thrombosis (venous or arterial) or other vascular complications within the last 6 months, or any history of either recurrent thrombosis or a pulmonary embolus.
o Note: Any participant being treated for recurrent antiphospholipid syndrome or anticardiolipin antibodies must be adequately anticoagulated according to current guidelines.
• 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 TB and atypical mycobacterial disease, granulomatous disease on chest x ray) that would substantially increase the risk to the participant if he or she participates in the study.

See section 5.2 of the Protocol for a full list of Exclusion Criteria

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified