A clinical study with placebo to evaluate the safety and efficacy of BMS-986165 when used with background medication in patients with Lupus Nephritis

Phase 1

• Conditions: upus Nephritis; MedDRA version: 21.1Level: PTClassification code 10025140Term: Lupus nephritisSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2018-004142-42-BE
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-12
• Last Update Posted: 29 November 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 113

Inclusion Criteria

Signed Written Informed Consent
a. Willing to participate in the study and have the ability to give informed consent
b. Willing and able to complete all study-specific procedures and visits

SLE Disease Characteristics
a. Meets the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria for SLE
b. Renal biopsy confirming a histologic diagnosis of active LN ISN/RPS Classes III (A or A/C), IV-S (A or A/C), or IV-G (A or A/C); or Class V (in combination with Class III or IV)
c. UPCR = 1.5 mg/mg assessed with a 24-hour urine specimen

Medications for SLE/Concomitant Medications
a. Prospective subjects may have been taking MMF for up to 12 weeks (but not more than 12 weeks) at the time of screening, with a suggested target dose of 1.5 to 2.0 g/day (maximum 3.0 g/day) unless limited by toxicity or intolerance; eligible subjects not taking MMF at screening will begin treatment with MMF in Part A
b. If subjects are taking an angiotensin converting enzyme inhibitor, angiotensin receptor blocker, or antimalarial drug, the dose must be stable for at least 4 weeks before randomization into part B with no anticipated changes in dosage in Part B
c. Required discontinuation periods for other immunomodulatory drugs or biologic drugs must be met as outlined in APPENDIX 7. If a specific drug is not listed, consult the PRA medical monitor for guidance; usual discontinuation periods are 4 weeks or 5 half-lives, whichever is longer

Age and Reproductive Status
a. Men and women aged 18 to 75 years inclusive at the time of screening
b. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin) at screening, within 24 hours before the first dose of MMF in Part A, and before the first dose of blinded study treatment in Part B.
c. Women must not be breastfeeding
d. The contraception requirements for MMF are stricter than those for BMS-986165; therefore the requirements for MMF (see APPENDIX 4) must be followed throughout study participation and for a period of time after the final dose of MMF or blinded study treatment
1. WOCBP:
a. Per the MMF prescribing information, subjects taking MMF must use acceptable contraception throughout the study and continue for at least 6 weeks after the final dose of MMF
b. Subjects must be counseled that MMF may reduce the effectiveness of oral contraceptives, and use of additional barrier contraceptive methods is required
2. Men who are sexually active with WOCBP:
a. Subjects must inform any and all partners of their participation in the study and the need to use contraception during the man’s study participation and for at least 90 days after his last dose of MMF
b. Per the MMF prescribing information, male subjects taking MMF must continue to use effective contraception and should not donate sperm for at least 90 days after the final dose of MMF
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 113
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23

Exclusion Criteria

Target Disease
a. Pure ISN/RPS Class V membranous LN
b. Screening estimated glomerular filtration rate (eGFR; calculated using the MDRD equation) = 30 mL/minute/1.73 m2
c. Dialysis within 12 months before screening or plans for dialysis within 6 months after enrollment
d. History of kidney transplantation or planned transplantation during the study
e. End-stage renal disease
f. Autoimmune diseases other than SLE, with the exception of secondary Sjögren’s syndrome, celiac disease, and stable Hashimoto’s thyroiditis
g. SLE overlap syndromes such as mixed connective tissue disease or coexisting scleroderma or rheumatoid arthritis
h. Antiphospholipid Syndrome (APS):
i. Active or unstable lupus neuropsychiatric manifestations, including but not limited to any condition defined by British Isles Lupus Assessment Group (BILAG) A criteria, with the exception of subjects with mononeuritis multiplex and polyneuropathy, which are allowed with the approval of CRS.

Other Medical Conditions and History
a. Women who are pregnant or breastfeeding
b. Screening systolic blood pressure > 150 and/or diastolic blood pressure > 90 mmHg
c. BMI = 40 kg/m2 at screening
d. Any major illness/condition, evidence of an unstable clinical condition, or symptoms of a severe, progressive, or uncontrolled condition or local active infection/infectious illness that might place the subject at unacceptable risk for participation in this study
e. Any major surgery within 30 days before the first dose of study treatment or any surgery planned during the course of the study
f. Cancer or history of cancer or lymphoproliferative disease within 5 years before screening
g. New York Heart Association (NYHA) Class III or IV congestive heart failure or any recent onset of heart failure resulting in NYHA Class III/IV symptoms
h. Acute coronary syndrome and/or any history of significant cerebrovascular disease within 24 weeks before screening
i. Serious thrombotic event(s) within 1 year before the screening visit
j. Current or recent gastrointestinal disease, including gastrointestinal surgery, that could impact the absorption of oral study treatment
k. Non-SLE concomitant illness that is likely to require additional systemic glucocorticosteroid therapy during the study
l. Severe, progressive, or uncontrolled kidney, liver, blood, stomach, lung, heart, or brain disease not due to active SLE
m. Comorbid conditions requiring systemic corticosteroid use in the 52 weeks before screening
n. Poorly controlled or advanced diabetes mellitus, as evidenced by a hemoglobin A1c of = 8.0% at screening, or by active diabetic complications such as diabetic nephropathy
o. Evidence of a degree of tubulointerstitial changes that suggest a significant and irreversible decrease in renal function
p. Renal disease unrelated to SLE including persistent, non-SLE-related pyuria or hematuria
q. Significant blood loss (> 500 mL) or blood transfusion within 4 weeks before randomization
r. Inability to tolerate oral medication
s. Inability to tolerate venipuncture and/or inadequate venous access
t. Recent substance dependence or abus
u. Any disease or medical condition that would make the subject unsuitable for this study, would interfere with the interpretation of subject safety or study results, or considered unsuitable by the investigator for any other reason

Findings Related to Possible Infection
a. Evidence of active or latent tuberculosis (TB)
b. Any of the following hepatitis B (HBV), hepatitis C virus

Study & Design

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