Lupus Nephritis
Conditions
Brief summary
The purpose of this research is to study the safety and efficacy of daratumumab in inducing complete or partial remission in patients with active lupus nephritis.
Interventions
DRUGDaratumumab
1800 mg administered by subcutaneous injection by manual push over approximately 3-5 minutes in the abdominal subcutaneous tissues in the left/right locations, alternating between individual doses.
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years of age. * Diagnosis of SLE according to current American College of Rheumatology (ACR) criteria. * Renal biopsy confirming the diagnosis of active class III/IV (± class V) LN (based on International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003) within 12 months of enrollment. * Proteinuria ≥ 500 mg over 24 hours. * eGFR ≥ 30 ml/min/SA. * Subjects should be able to give informed consent.
Exclusion criteria
* Pregnancy. * Hepatitis B or C, HIV * Anemia with Hgb \< 8.0 g/dL. * Thrombocytopenia with platelet count \< 100'000. * Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complication. * Unable to provide consent. * Patients receiving \> 10 mg of oral prednisone or glucocorticoid equivalent if on corticosteroids for \> 2 weeks (patients would be allowed to be on \> 10 mg of prednisone or its oral equivalent as long as the duration is ≤ 2 weeks). * Patients who had received immunosuppressive therapy including cyclosporine, tacrolimus or azathioprine in the last 3 months. * Patients who have received cyclophosphamide in the last 6 months. * Patients who received rituximab previously with CD20 count of zero at the time of enrollment. * Patient are allowed to be on MMF at time of enrollment but no higher than total of 1500mg/day. * For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of less than (\<) 1 percent (%) per year, during the treatment period and for at least 12 months after the last dose of study drug. * For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for at least 12 months after the last dose of study drug and agreement to refrain from donating sperm during this same period. * Patients with diagnosis of glaucoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of daratumumab in inducing complete(CR) or partial(PR) renal remission in patients with active class III or IV Lupus Nephritis | 12 months after first infusion of Daratumumab | Complete Renal Response:- \< 500 mg proteinuria/24 hours, Inactive urinary sediment (\<10 RBC/HPF and absence of RBC casts), No greater than a 15% reduction in eGFR from enrollment |
| Efficacy of daratumumab in inducing complete(CR) or partial(PR) | 12 months after first infusion of Daratumumab | Partial Renal Response: \> 50% reduction in 24-hour proteinuria and proteinuria \< 1g/24hr if baseline 24hr proteinuria, - ≤3 g/24hr and proteinuria ≤ 3 g/24hr if starting proteinuria \> 3 g/24hrs. , Improved urinary sediment (\>=50% reduction in RBC/HPF and absence of RBC casts), No greater than a 20% reduction in baseline eGFR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of daratumumab in patients with active class III/IV LN. | 24 months after first infusion of Daratumumab | Incidence of major infections defined in the development of pneumonia, grade 3 urinary tract infection/pyelonephritis, sepsis, meningitis or anemia. |
| Improvement from proteinuria | Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab | Change in proteinuria in milligrams (mg) per 24h |
| Change in hematuria. | Baseline,6, 12, 18 and 24 months after first infusion of Daratumumab | Improvement in hematuria from baseline as measured by the urinalysis |
| Improvement in eGFR | Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab | Improvement in eGFR measured using the chronic kidney disease epidemiology collaboration (CKD-EPI) Equation: eGFR (CKD-EPI) = 141 x min(Scr/k, 1)alpha x max(Scr/k,1)-1.209 x 0.993age x 1.018 (if patient is female) x 1.159 (if patient is black) |
| Change in ds-DNA | Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab | Improvement in ds-DNA in International units per milliliter (IU/mL) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFernando Fervenza, MD
Mayo Clinic
Outcome results
None listed