A clinical study to test the efficacy and safety of BMS-986165 in Subjects with Systemic Lupus Erythematosus.

• Register: EUCTR
• Last refreshed on: 17 January 2022
• Main ID: EUCTR2017-001203-79-HU
• Date of registration: 04/10/2017
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb international Corporation
• Public title: A clinical study to test the efficacy and safety of BMS-986165 in Subjects with Systemic Lupus Erythematosus.
• Scientific title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BMS-986165 in Subjects with Systemic Lupus Erythematosus
• Date of first enrolment: 04/12/2017
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001203-79
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Bulgaria, Colombia, France, Germany, Hungary, Israel, Japan, Korea, Republic of, Mexico, Peru, Poland, Romania, Russian Federation, Spain, Taiwan, Ukraine, United States

Contacts

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
1) Signed Written Informed Consent
2) SLE Disease Characteristics
a) Diagnosed = 24 weeks before the screening visit
b) Meets the SLICC classification criteria for SLE9.
c) One of the following: elevated antinuclear antibodies = 1:80 or positive
anti-dsDNA 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 score.
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).
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. 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 formulations are prohibited.
c) Requirements for subjects who are receiving chronic therapy with NSA
Exclusion criteria:
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 within 1 year before the screening visit . Subjects with a history of catastrophic antiphospholipid syndrome or saddle embolism.
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 and History:
a) Any major illness/condition that will substantially increase the risk to the subject if he or she participates in the study.
b) Any major surgery within the last 30 days before the first dose of study treatment, or any
surgery planned during the study.
c) Cancer or history of cancer or lymphoproliferative disease within 5 years
d) Class III or IV congestive heart failure
e) Acute coronary syndrome and/or any history of significant cerebrovascular disease within 24 weeks of screening
f) Current or recent (within 3 months before randomization) gastrointestinal disease,
including surgery, that could impact the absorption of study treatment
g) Subjects with non-SLE concomitant illness that is likely
to require additional systemic glucocorticosteroid therapy
h) Significant blood loss (> 500 mL) or blood transfusion within 4 weeks of
randomization
i) Inability to tolerate oral medication
j) Inability to undergo venipuncture and/or tolerate venous access
k) Recent (within 6 months of randomization) drug or alcohol abuse.
3) Prior/Concomitant Therapy
a) Inability to comply with restrictions and prohibited treatments or to
comply with discontinuation requirements.
b) Taking more than 1 immunosuppressant.
c) Prior exposure to Tyk2 inhibitors
d) Prior exposure to anifrolumab or rontalizumab
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 before
screening
? Subjects with negative chest x-ray within 6 months of screening may be
eligible if:
o negative IFN gamma release assay (IGRA)
o positive IGRA and no symptoms of active TB, and have previously (within
5 years) received adequate documented treatment for latent TB
o positive IGRA and no symptoms of active TB, but have NOT previously (within 5 years) received adequate documented treatment; subject must initiate prophylactic treatment per local guidelines and may rescreen after 1 month of treatment
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.
Subjects vaccinated for hepatitis B (hepatitis B surface antibody [anti-HBs].
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 histor

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Immune system processes [G12]

Systemic Lupus Erythematosus
MedDRA version: 20.0 Level: LLT Classification code 10042947 Term: Systemic lupus erythematosus synd System Organ Class: 100000017968

Intervention(s)

Product Name: BMS-986165
Product Code: BMS-986165
Pharmaceutical Form: Capsule
INN or Proposed INN: BMS-986165
CAS Number: 1609392-28-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the effect of BMS-986165 on measures of global and organ-specific
SLE clinical response.

To assess the safety and tolerability of BMS-986165.

To assess the PK of BMS-986165 in subjects with SLE.

To assess the effect of BMS-986165 on PD markers.

Primary end point(s): Proportion of subjects who achieve BICLA response at Week 32 after treatment
with BMS-986165 or placebo administered on stable background therapy

Timepoint(s) of evaluation of this end point: 32 weeks

Main Objective: To assess the effect of BMS-986165 on BICLA response at Week 32 in subjects
with SLE

Secondary Outcome(s)

Secondary end point(s): Efficacy:
- Proportion of subjects who meet response criteria for SLE Responder Index (SRI)(4)
- Proportion of subjects with a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score = 10 at baseline who achieve a CLASI response, defined as a decrease of = 50% from baseline CLASI activity score - Change from baseline in the 40-joint count for tender, swollen, and
tender + swollen joints
Safety:
- Number and proportion of subjects experiencing serious adverse events (SAEs), AEs, and abnormalities in laboratory testing, vital signs, and electrocardiograms (ECGs)
Pharmacokinetics:
Trough concentrations of BMS-986165
Pharmacodynamics:
o Change in mean and median interferon-regulated gene (IRG) expression levels
compared to baseline over time and at Week 32
o Change in mean complement (C3, C4) and anti-double-stranded DNA (dsDNA)
levels compared to baseline over time and at Week 32
o Assess the effect of BMS-986165 on measures of global SLE clinical response in
subjects based on IRG status (ie, high versus low IRG signature) at Week 32

Timepoint(s) of evaluation of this end point: Efficacy - Week 32
Safety - Throughout the study
Pharmacokinetics - at Weeks 2, 4, 8, 12, 24, 32, and 48
Pharmacodynamics - Week 32

Secondary ID(s)

IM011021

Source(s) of Monetary Support

Bristol-Myers Squibb Research and Development

Ethics review

Status: Approved
Approval date: 14/11/2017
Contact: