Daratumumab to Treat Active Lupus Nephritis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Daratumumab

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amber Stanton; Phone Number: 507-293-7259; Email: Stanton.Amber@mayo.edu
• Study Contact Backup: Name: Angela Reinke; Phone Number: 507-266-1047; Email: Reinke.Angela@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Amber Stanton; Phone Number: 507-293-7259; Email: Stanton.Amber@mayo.edu
      • Principal Investigator: Fernando Fervenza, M.D.
      • Sub-Investigator: Zand Ladan, M.D.
      • Contact: Angela Reinke; Phone Number: 507-266-1047; Email: Reinke.Angela@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daratumumab; 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; 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.

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Fernando C Fervenza, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis; Lupus Nephritis; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: 20-010520

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Plan pending

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No