Daratumumab to Treat Active Lupus Nephritis

Study Overview
=================
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.

Official Title
-----------------
A Phase 2 Open-label Trial Evaluating the Efficacy and Safety of Daratumumab in Treatment of Patients With Active Lupus Nephritis

Conditions
-----------------
Lupus Nephritis

Intervention / Treatment
-----------------
* Drug: Daratumumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daratumumab<br>Subjects diagnosed with lupus nephritis will receive Daratumumab once weekly for 8 weeks and then once every 2 weeks for 8 additional does (+/- 4 days). Subjects will be followed for a total of 24 months (18 months after the last daratumumab administration). | Drug: Daratumumab<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of daratumumab in inducing complete(CR) or partial(PR) renal remission in patients with active class III or IV Lupus Nephritis | 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 | 12 months after first infusion of Daratumumab | 
| Efficacy of daratumumab in inducing complete(CR) or partial(PR) | 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 | 12 months after first infusion of Daratumumab | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of daratumumab in patients with active class III/IV LN. | Incidence of major infections defined in the development of pneumonia, grade 3 urinary tract infection/pyelonephritis, sepsis, meningitis or anemia. | 24 months after first infusion of Daratumumab | 
| Improvement from proteinuria | Change in proteinuria in milligrams (mg) per 24h | Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab | 
| Change in hematuria. | Improvement in hematuria from baseline as measured by the urinalysis | Baseline,6, 12, 18 and 24 months after first infusion of Daratumumab | 
| Improvement in eGFR | 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) | Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab | 
| Change in ds-DNA | Improvement in ds-DNA in International units per milliliter (IU/mL) | Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab |