i

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of BIIB059 in Adult Participants With Active Systemic Lupus Erythematosus Receiving Background Nonbiologic Lupus Standard of Care

PHRR211102-004038

230LE303

2021-CT0631

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of BIIB059 in Adult Participants With Active Systemic Lupus Erythematosus Receiving Background Nonbiologic Lupus Standard of Care

This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study designed to evaluate the efficacy and safety of BIIB059 in participants ≥ 18 years of age with active SLE, including joint and/or skin manifestations, who are receiving background nonbiologic lupus SOC therapy. The study will be conducted at approximately 135 sites globally. Approximately 540 participants will be randomized 1:1:1 to receive BIIB059 450 mg, BIIB059 225 mg, or placebo SC Q4W, with an additional dose at Week 2, as add-on to background nonbiologic lupus SOC therapy.

The study includes a screening period of up to 4 weeks; a double-blind, placebo-controlled treatment period of 52 weeks; and an SFU period (off-treatment) of 24 weeks

Regime Classification Priority
2017 - 2022 Research to enhance and extend healthy lives Access to essential medical products, vaccines and technologies
Start Date Duration in Months Target Completion Date Actual Completion Date
2021-11-15 20 2023-07-15 0000-00-00

Pending

CT Agreement not yet available

Institution Classification Region LTO #
IQVIA RDS Philippines, Inc. Private Business NCR LTO-3000005977146
Institution Classification Region LTO #
Biogen Idec Research Limited Private Business United Kingdom NA
Institution Region
Biogen Idec Research Limited United Kingdom
Name E-Mail Institution and Institution Address
Marissa Laureta marissa.laureta@iqvia.com IQVIA RDS Philippines Inc., Unit A, 7th Flr. 8 Rockwell Bldg., Hidalgo Drive, Rockwell Center, Makati City 1210
Name E-Mail Institution and Institution Address
Biogen Idec Research Limited NA Biogen Idec Research Limited, Innovaive House 70 Norden Road Maidenhead, Berkshire SL64 AY United Kingdom
Name Expertise Affiliation
Allan E. Lanzon, MD Rheumatologist Philippine General Hospital
Caroline G. Arroyo, MD Rheumatologist Iloilo Doctor's Hospital
Edgar Ramiterre, MD Rheumatologist Southern Philippines Medical Center
Harold Michael P. Gomez, MD Rhheumatologist Angeles University Foundation Medical Center
Juan Javier T. Lichauco, MD Rheumatologist St. Luke's Medcal Center Quezon City
Llewellyn T. Hao, MD Rheumatologist Davao Doctors Hospital
Michael L. Tee, MD Rheumatologist ManilaMed - Medical Center Manila
Noriezel V. Arcigal-Trinidad, MD Rheumatologist The Medical City
Rosario P. Baes, MD Rheumatologist Far Eastern University-Nicanor Reyes Medical Foundation
Sorrah Fiel R. Briones, MD Rheumatologist University of Santo Tomas Hospital
Project Location Institutional Ethics Review Board
Philippine General Hospital Philippine General Hospital Research Implementation and Development Office
Iloilo Doctor's Hospital Ethics Review Committee Iloilo Doctor's Hospital
Southern Philippines Medical Center Southern Philippines Medical Center
Angeles University Foundation Medical Center Angeles University Foundation Medical Center Institutional Ethics Review Committee
St. Luke's Medcal Center Quezon City St. Luke's Medical Center Institutional Ethics Review Board
Davao Doctors Hospital Davao Doctors Hospital Ethics Review Committee
ManilaMed - Medical Center Manila Medical Center Manila Ethics Review Board
The Medical City The Medical City - Institutional Review Board
Far Eastern University-Nicanor Reyes Medical Foundation Far Eastern University - Nicanor Reyes Memorial Foundation Hospital Ethics Review Committee
University of Santo Tomas Hospital University of Santo Tomas Hospital Institutional Review Board

Adult Participants With Active Systemic Lupus Erythematosus

 Proportion of participants who achieved an SRI-4 response at Week 52.

The composite endpoint SRI-4 is defined by the following criteria: i. A reduction from Baseline of ≥ 4 points in SLEDAI-2K score; and ii. No new organ system affected, as defined by no new organ system with BILAG-2004 grade A and no more than 1 new organ system with BILAG-2004 grade B compared with Baseline; and iii. No worsening from Baseline in lupus disease activity as defined by < 0.3-point increase on 3-point PGA-VAS; and iv. No changes to protocol-specified medication rules.

Proportion of participants who achieved an SRI-4 response at Week 24.

Proportion of participants with at least 4 joints (both swollen and tender) at Baseline who achieved a Joint-501,2 response at Week 52.

Proportion of participants with OCS ≥ 10 mg/day at Baseline who have OCS reduction to ≤ 7.5 mg/day at Week 40, which is sustained through Week 52 with no disease worsening4 from Week 40 to Week 52.

Proportion of participants with a CLASI-A score ≥ 10 at Baseline who achieved a CLASI-505 response at Week 16. Annualized flare rate6 through Week 52.

Pending

Clinical Trial

230LE303

20210729104407

2021-10-11

2021-10-11

50

Unspecified

Unspecified

0000-00-00

Inclusion Criteria 1. Ability of the participant to understand the purpose and risks of the study, to provide informed consent, and to authorize the use of confidential health information in accordance with national and local privacy regulations. 2. Participant must be ≥ 18 years of age at the time of signing the ICF. 3. All women of childbearing potential must practice effective contraception during the study treatment period and for 90 days after their last dose of study treatment. In addition, participants should not donate eggs during the study treatment period and for at least 90 days after their last dose of study treatment. Where applicable, postmenopausal status must be confirmed as follows: for women ≤ 55 years of age, 52 continuous weeks of natural (spontaneous) amenorrhea without an alternative medical cause and a serum FSH level ≥ 40 mIU/mL; for women > 55 years of age, 52 continuous weeks of natural (spontaneous) amenorrhea without an alternative medical cause and a serum FSH level ≥ 40 mIU/mL, or at least 5 continuous years of natural (spontaneous) amenorrhea without an alternative medical cause. 4. Participant must be diagnosed with SLE at least 24 weeks prior to Screening and must meet the 2019 EULAR/ACR classification criteria for SLE (see Appendix C), at Screening by a qualified physician [Aringer 2019]. 5. Participant has a modified SLEDAI-2K score ≥ 6 (excluding alopecia, fever, lupus-related headache, and organic brain syndrome) at Screening (adjudicated) and randomization, as follows:  If 4 points of the required SLEDAI-2K entry points are for arthritis, there must also be at least 4 joints that are both swollen and tender (with at least 4 occurring in the PIP, MCP, or wrist joints), based on the 28-joint count assessment described in Appendix A.  If 2 points of the required SLEDAI-2K entry points are due to rash, the rash must be attributable to ACLE, SCLE, and/or CCLE (e.g., DLE) skin manifestation. 6. Participant has a modified clinical SLEDAI-2K score ≥ 4 (excluding anti-dsDNA, low complement C3 and/or C4, alopecia, fever, lupus-related headache, and organic brain syndrome) at Screening (adjudicated) and randomization. 7. Participant has BILAG-2004 grade A in ≥ 1 organ system or BILAG-2004 grade B in ≥ 2 organ systems at Screening (adjudicated) and randomization. 8. Participant must be treated with one of the following background nonbiologic lupus SOC therapies, initiated ≥ 12 weeks prior to Screening and at stable dose ≥ 4 weeks prior to randomization (see Section 7.7.1):  Antimalarials as stand-alone treatment  Antimalarial treatment in combination with OCS and/or immunosuppressants  Treatment with OCS and/or immunosuppressants 9. Participant has one of the following results, per the central laboratory at Screening:  ANA ≥ 1:80 by immunofluorescent assay  Anti-dsDNA above normal levels  Anti-Smith antibody above normal levels

Exclusion Criteria Medical History and Current Health Status 1. History of or positive test result for HIV. 2. Current hepatitis C infection (defined as positive HCV antibody and detectable HCV RNA). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study (United States Centers for Disease Control and Prevention). Note: Eligible participants with risk for HCV exposure can be tested every 6 months during the study at the discretion of the Investigator. 3. Current hepatitis B infection (defined as positive for HBsAg and/or total anti-HBc). Participants with the following immune profiles according to United States Centers for Disease Control and Prevention are eligible to participate in the study:  Immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-HBs); or  Previous vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs). 4. History of chronic, recurrent (3 or more of the same type of infection in a 52-week period), or recent serious infection (e.g., pneumonia, septicemia), including viral infections, as determined by the Investigator, or requiring anti-infective treatment within the 12 weeks prior to Screening. 5. History of severe herpes infection, such as herpetic encephalitis, ophthalmic herpes, or disseminated herpes. 6. Signs of herpes or varicella zoster viral infection (specifically chicken pox, shingles, or herpes zoster) within 12 weeks prior to Screening. 7. Exclusion related to SARS-CoV-2-specific criteria is described in Appendix B. Testing must be done by PCR where available and may be conducted by the central laboratory selected by the Sponsor or locally as follows: At Screening:  Previous positive test (within 14 days prior to Screening). At randomization:  Positive test (within 14 days prior to randomization); or  Evidence of SARS-CoV-2 infection. Symptoms suggestive of SARS-CoV-2 infection may include, but are not limited to, any of the following:  Fever (temperature > 37.5°C), chills, cough, shortness of breath, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea. The Investigator should assess the participant’s condition holistically when determining evidence of SARS-CoV-2 infection; or  Close contact with an individual with SARS-CoV-2 infection within 14 days prior to randomization. Close contact is defined as follows or according to local guidance:  Being within 6 feet (1.8 meters) of an infected individual (as confirmed by laboratory assessment) for a cumulative total of 15 minutes or more over a 24-hour period within 2 days of symptom onset; or  Being within 6 feet (1.8 meters) of an asymptomatic infected individual (as confirmed by laboratory assessment) for a cumulative total of 15 minutes or more over a 24-hour period within 2 days of that asymptomatic individual undergoing specimen collection for SARS-CoV-2 testing; or  Being in direct physical contact with, or providing direct care for, an individual with probable or confirmed SARS-CoV-2 infection without using proper personal protective equipment; or  Other situations as indicated by local risk assessments. 8. History of or current diagnosis of active TB or untreated LTBI, as determined by a positive QuantiFERON® TB Gold Plus test result, or positive T-SPOT® test result performed by the central laboratory or locally either at Screening or documented with results within 12 weeks of Screening. Participants with documented history of Bacille Calmette-Guerin vaccination must undergo a QuantiFERON TB Gold Plus or a T-SPOT test at Screening. Participants who have previously completed appropriate and documented LTBI treatment will not be required to be tested.  Participants must have received complete LTBI treatment prior to Screening without evidence of re-exposure prior to entering the study, at the Investigator’s discretion.  Participants with current household contacts with active TB will be excluded, unless the participant is being treated and there is evidence that household contacts are being treated.  Indeterminate QuantiFERON TB Gold Plus or borderline or invalid T-SPOT tests may be repeated once, and participants will be excluded if the retest result exhibits a positive or indeterminate QuantiFERON TB Gold Plus or a positive or borderline T-SPOT test.  In case of retest, QuantiFERON TB Gold Plus or T-SPOT can be used interchangeably. If the T-SPOT test results are invalid both times or if the T-SPOT retest result is invalid, the Investigator can exclude the participant or test the participant one more time using QuantiFERON TB Gold Plus.  Where mandated by local regulation, a chest X-ray will be obtained locally during the screening period, unless a previous chest X-ray or the documented results from a chest X-ray obtained within 12 weeks prior to Screening are available. The chest X-ray or X-ray results will be reviewed by the Investigator (or designee) to exclude participants with active TB infection from entering the study. 9. Presence of uncontrolled or New York Heart Association class III or IV congestive heart failure. 10. History of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease beyond lupus that would preclude administration of BIIB059 as determined by the Investigator. 11. History of, or ongoing, malignant disease, including solid tumors and hematologic malignancies with the exception of basal cell carcinomas of the skin, squamous cell carcinomas of the skin, and carcinoma in situ of the cervix that have been completely excised and considered cured for > 2 years prior to Screening. For cervical neoplasia, based on the classification used locally, participants with cervical intraepithelial neoplasia (CIN) grades 2 or 3; or low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion according to the Bethesda system; as well as participants with a medical history of positive results for high-risk types of human papilloma virus will be excluded. 12. Active severe lupus nephritis where, in the opinion of the Investigator, protocol-specified SOC is insufficient and use of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high-dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated; or urine protein-creatinine ratio > 2.0 or severe chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m2 ) calculated using the abbreviated Modification of Diet in Renal Disease equation. 13. Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE and systemic sclerosis, as noted below:  An overlap syndrome of SLE with myositis at Screening is permitted, provided the participant also meets the criteria for the classification as SLE; or  A past history of mixed connective tissue disease that over time has developed into a diagnosis of SLE is permitted, provided diagnosis of SLE has been present for at least 1 year. 14. Any active skin conditions other than CLE that may interfere with the study assessment of CLE such as but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE skin lupus manifestation (e.g., cutaneous vascular disease, periungual telangiectasia, sclerodactyly, rheumatoid nodules, erythema multiform, leg ulcers), or drug-induced lupus. 15. History or current diagnosis of a clinically significant non-SLE-related vasculitis syndrome (see Appendix D). 16. Active neuropsychiatric SLE including, but not limited to, the following: seizure, new or worsening impaired level of consciousness, psychosis, delirium or confusional state, aseptic meningitis, ascending or transverse myelitis, chorea, cerebellar ataxia, mononeuritis multiplex, or demyelinating syndromes that would make the participant unable to fully understand the ICF; or where in the opinion of the Investigator, protocol-specified background nonbiologic lupus SOC therapy is insufficient and use of a more aggressive therapeutic approach such as adding IV cyclophosphamide and/or high-dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol is indicated. 17. History of suicide attempt or suicidal ideation within 1 year prior to Screening. 18. History of substance abuse within 6 months prior to Screening or a positive urine drug test at Screening. Medical marijuana may be used per discretion of the Investigator (see Section 7.7.1.1.2). 19. History of known hypersensitivity to BIIB059 or any components of the formulated BIIB059 or matching placebo 20. Antimalarial agents that were initiated less than 12 weeks prior to Screening, have not been at an allowed stable dose for at least 4 weeks prior to randomization, or have been taken during the 12 weeks prior to Screening at doses above the prescribed maximum listed here: hydroxychloroquine 400 mg/day, chloroquine 250 mg/day, or quinacrine 100 mg/day. 21. Immunosuppressive or disease-modifying treatments for SLE that were initiated less than 12 weeks prior to Screening, have not been at an allowed stable dose for at least 4 weeks prior to randomization, or have been taken during the last 12 weeks prior to Screening at doses above the prescribed maximum listed here: azathioprine 200 mg/day, mycophenolate either as MMF 3000 mg/day or MPS 2160 mg/day, 6-mercaptopurine 100 mg/day, dapsone 150 mg/day, or methotrexate 25 mg/week. 22. Use of oral prednisone (or equivalent) above 20 mg/day. 23. Use of high-potency topical corticosteroid and/or topical agents (immunosuppressive) for skin lesions within 1 week prior to Screening and during the study. 24. Use of high-potency intralesional corticosteroid within 1 week prior to Screening and during the study. 25. Use of IV or IM corticosteroids or intra-articular corticosteroids within 12 weeks prior to Screening and during the study. 26. Use of cyclosporine or voclosporin within 4 weeks prior to Screening and during the study. 27. Use of leflunomide within 24 weeks prior to Screening and during the study. 28. Use of tacrolimus, pimecrolimus, or sirolimus within 4 weeks prior to Screening and during the study. 29. Use of IV cyclophosphamide or mizoribine within 24 weeks or 5 half-lives, whichever is longer, prior to Screening and during the study. 30. Use of IV or SC immunoglobulin or plasmapheresis within 12 weeks prior to Screening and during the study. 31. Use of rituximab, ofatumumab, obinutuzumab, ocrelizumab, veltuzumab, or other B cell-directed biologic therapies within 24 weeks prior to Screening and during the study. Participants with prior B cell-directed therapies within 12 months of Screening will be excluded if total CD19 B cell level is < 25 cells/µL as measured at a central laboratory at Screening. 32. Use of abatacept (CTLA4-Ig), tocilizumab, belimumab, or TNF inhibitors within 12 weeks or 5 half-lives, whichever is longer, prior to Screening and during the study. 33. Use of ustekinumab, atacicept, or telitacicept within 24 weeks prior to Screening and during the study. 34. Use of thalidomide or lenalidomide within 8 weeks prior to Screening and during the study. 35. Use of minocycline within 4 weeks prior to Screening and during the study. 36. Medical Monitor must be contacted prior to Screening in case of use of other investigational drug or off-label drug used to treat SLE, cutaneous lupus, or lupus nephritis that is not mentioned in the preceding criteria. 37. Use of any investigational therapy not mentioned in the preceding criteria within 24 weeks or 5 half-lives, whichever is longer, prior to Screening and during the study. 38. Previous treatment with investigational or approved agents that inhibit the IFN-α pathway. 39. Immunizations with live or live-attenuated vaccines within 4 weeks prior to Screening and throughout the study and for 24 weeks after the last dose of study treatment. Other 40. Blood donation of ≥ 500 mL within the 4 weeks prior to Screening or plans to donate blood during the course of study. 41. Aspartate aminotransferase or alanine aminotransferase > 2.0 times the upper limit of normal. 42. Hemoglobin < 5.5 mmol/L (9 g/dL), neutrophils < 1.5 × 109 /L, or platelets < 75 × 109 /L. 43. Any abnormal laboratory test result that is considered clinically significant, as determined by the Investigator, and would preclude the participant from participating in the study. An out-of-range laboratory value that is not clinically significant would not be considered exclusionary. 44. Plans to undergo elective procedures or surgeries from the initial Screening Visit until the last SFU Visit. 45. Female participants who are pregnant, currently breastfeeding, or planning to become pregnant during the study treatment period and for 90 days after their last dose of study treatment. 46. Previous enrollment in this study or previous participation in studies with BIIB059, with the exception of those who received placebo. 47. Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 5 half-lives of the agent prior to Screening (participation in observational registries is allowed). 48. Inability to comply with study requirements. 49. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the participant unsuitable for enrollment.

Interventional

BIIB059

BIIB059 (anti-blood dendritic cell antigen 2 [anti-BDCA2]) is a fully humanized, Fc (fragment crystallizable) effector functioncompetent immunoglobulin G1 (IgG1) monoclonal antibody (mAb) with a molecular weight of approximately 149 kDa. BIIB059 is supplied as a sterile liquid formulation for intravenous (IV) and subcutaneous (SC) administration. Two strengths and 3 formulations of the investigational product are provided:  50 mg/mL BIIB059, sodium citrate, L-arginine hydrochloride, polysorbate 80, and pH 6.0 (formulation used in Phase 1)  150 mg/mL BIIB059, histidine, L-arginine hydrochloride, sucrose, polysorbate 80, and pH 5.5 (formulation used in Phase 2)  150 mg/mL BIIB059, histidine, L-arginine hydrochloride, sucrose, glutathione, polysorbate 80, and pH 5.7 (formulation to be used in the future studies)

Date Amendment Classification Reason
2021-12-21 Amendments related to the protocol Informed consent

Randomized

Double Blind

The study includes a screening period of up to 4 weeks; a double-blind, placebo-controlled treatment period of 52 weeks; and an SFU period (off-treatment) of 24 weeks. Details of these different study periods are given below.

Parallel

To demonstrate efficacy of BIIB059 compared with placebo in participants with active SLE, who are receiving background lupus SOC therapy in reducing disease activity

Phase III

Utilization Utilization Info
Publication
Oral Presentation
Drug Literature
Posters
Others
©2022 HERDIN PLUS. All rights reserved. | Contact Us | Keep up to date