A clinical study to test the efficacy and safety of BMS-986165 in Subjects with Systemic Lupus Erythematosus.
- Conditions
- Systemic Lupus ErythematosusMedDRA version: 21.1Level: LLTClassification code 10042947Term: Systemic lupus erythematosus syndSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2017-001203-79-DE
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 360
1) Signed Written Informed Consent
2) SLE Disease Characteristics
a) Diagnosed = 24 weeks before the screening visit
b) Meets the SLICC classification criteria for SLE.
c) One of the following: elevated antinuclear antibodies = 1:80 or positive anti-dsDNA( positive includes indeterminate results) or positive anti-Smith as determined by the central laboratory.
d) Total SLEDAI-2K score = 6 points and clinical SLEDAI-2K score = 4 points with joint involvement and/or rash
o Lupus headache, alopecia, organic brain syndrome, and mucosal ulcers cannot count toward the points required for screening at entry.
o Clinical SLEDAI-2K excludes laboratory abnormalities such as hematuria, pyuria, urinary casts, proteinuria, positive anti-dsDNA, decreased complement,
thrombocytopenia, and leukopenia.
e) At least 1 of the following BILAG-based protocol-specific manifestations of SLE:
i) BILAG A or B grade in the Mucocutaneous body system. If a BILAG B grade for
Mucocutaneous disease is due to BILAG #6 mild skin eruption, the total score of the erythema and scale components of the CLASI disease activity must be = 3 (excluding mucous membrane ulcerations and nonscarring alopecia).
ii) Modified BILAG A or B score in the Musculoskeletal body system due to active
polyarthritis.
iii) If only 1 B and no A grade is present in the Mucocutaneous body system or in the Musculoskeletal body system due to arthritis, then at least 1 B grade must be present in one of the other body systems, for a total of 2 BILAG B body system grades.
3) Medications for SLE
a) Background therapy is required for = 12 weeks before the screening visit and must be at a stable dose for = 8 weeks before the screening visit and remain stable until randomization and throughout study participation. Details for specific medications are as follows:
? Immunosuppressants (combinations of these are NOT permitted):
o azathioprine (maximum 200 mg/day)
o 6-mercaptopurine (6-MP)
o methotrexate (MTX; maximum 25 mg/week; dose and route of administration
of MTX may not be changed for 8 weeks before the screening visit and throughout study participation)
o leflunomide
o mycophenolate mofetil/ mycophenolic acid (MMF). Note: Subjects who are
receiving MMF may participate in the study only if administered as a
maintenance therapy and up to a maximum of 2 g/day (or equivalent); in subjects of African ancestry, 3 g/day (or equivalent) is acceptable. Treatment may be interrupted due to neutropenia per the product label.
? Antimalarials: chloroquine, hydroxychloroquine, or quinacrine; monotherapy is permitted.
? Required discontinuation periods for other immunomodulatory drugs or biologic drugs (are provided in Appendix 7 of the protocol.
b) CS (prednisone or equivalent) background therapy is permitted but not required. For subjects taking CS, the dose must be stable for = 2 weeks before the screening visit, cannot exceed 30 mg/day at screening, and must remain stable until randomization. CS monotherapy is not permitted. Prednisone equivalents are provided in Appendix 6. Further specifications are as follows:
? Intramuscular, intra-articular, intrabursal, and intravenous (IV) CS use is prohibited within 6 weeks before screening.
? Topical CS use is permitted, but must follow a stable regimen throughout the study and cannot be used on an as-needed basis.
? Inhaled CS for nonlupus conditions is permitted and will not count against the
maximum CS dose.
? Modified-release CS formulat
1) Target Disease Exceptions
a) Drug-induced SLE
b) Other autoimmune diseases are excluded.
c) SLE overlap syndromes such as scleroderma and mixed connective tissue disease are excluded.
d) Subjects with a serious thrombotic event or unexplained pregnancy loss within 1 year before the screening visit. Subjects with a history of catastrophic antiphospholipid syndrome or saddle embolism and history of pregnancy losses.
e) Active or unstable lupus neuropsychiatric manifestations, including but not limited to any condition defined by BILAG A criteria.
f) Active, severe lupus nephritis that requires or may require treatment with cytotoxic agents or high-dose CS.
2) Other Medical Conditions:
a)Women who are pregnant or breastfeeding
b) Any major illness/condition that will increase the risk with participation in the study
c) Any major surgery within the last 30 days before the first dose of study treatment or planned during the study.
d) Cancer or history of cancer or lymphoproliferative disease within 5 years
e) Class III or IV congestive heart failure
f) Acute coronary syndrome and/or any history of significant cerebrovascular disease within 24 weeks of screening
g) Current or recent (within 3 months pre-randomization) gastrointestinal disease, including surgery, that could impact the absorption of study treatment
h) Subjects with non-SLE concomitant illness that is likely to require additional systemic glucocorticosteroid therapy
i) Significant blood loss or blood transfusion within 4 weeks of randomization
j) Inability to take medication orally
k) Inability to undergo venipuncture and/or tolerate venous access
l) Recent (within 6 months of randomization) drug or alcohol abuse.
3) Prior/Concomitant Therapy
a) Inability to comply with restrictions and prohibited treatments or with discontinuation requirements.
b) Taking more than 1 immunosuppressant.
c) Prior exposure to Tyk2 inhibitors
d) Prior exposure to anifrolumab, rontalizumab or ustekinumab or interferon alpha kinoid
e) Other investigational agents must be discontinued at least 12 weeks or 5 half-lives before randomization, whichever is longer.
4) Findings Related to Possible Infection
a) Evidence of active or latent tuberculosis (TB):
? Positive chest x-ray for evidence of active pulmonary TB within 6 months pre-screening (some exceptions allowed)
? b) Hepatitis C, hepatitis B, or HIV infection as demonstrated by a positive blood screen for hepatitis C antibody (anti-HCV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or HIV-1 and -2 antibody.
c) Currently on any therapy for chronic infection
d) History of congenital or acquired immunodeficiency
e) Known active infection, or any major episode of infection requiring hospitalization or treatment with parenteral antimicrobial agents within 30 days of randomization, or completion of oral antimicrobial agents within 2 weeks of randomization
f) Previous history of herpes zoster, herpes simplex, or influenza infection within 12 weeks of randomization or a history of disseminated/complicated herpes zoster infection
g) Administration of a live vaccine within 90 days or an inactivated vaccine within 30 days of randomization. Furthermore, live vaccines should not be used during treatment or within the 2 months following last dose, and any other inactivated vaccines should be used according to local guidelines.
5) Physical and Laboratory Test Findings
a) Clinically signifi
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