Daratumumab to Treat Active Lupus Nephritis

Lupus Nephritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04868838
• Other study ID #: 20-010520
• Status: Recruiting
• Phase: Phase 2
• Start date: April 20, 2021
• Est. completion date: July 2026

Study information

• Verified date: May 2024
• Source: Mayo Clinic
• Contact: Nicholas Geroux
• Phone: 507-266-0956
• Email: geroux.nicholas[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

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.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Improvement from proteinuria	Change in proteinuria in milligrams (mg) per 24h	Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab
Secondary	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
Secondary	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
Secondary	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