Daratumumab to Treat Active Lupus Nephritis

Sponsor
Mayo Clinic (Other)
Overall Status
Recruiting
CT.gov ID
NCT04868838
Collaborator
(none)
12
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Open-label Trial Evaluating the Efficacy and Safety of Daratumumab in Treatment of Patients With Active Lupus Nephritis
Actual Study Start Date :
Apr 20, 2021
Anticipated Primary Completion Date :
May 1, 2023
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. 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

  2. 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 Outcome Measures

  1. 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.

  2. Improvement from proteinuria [Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab]

    Change in proteinuria in milligrams (mg) per 24h

  3. 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

  4. 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)

  5. 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)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Mayo Clinic in Rochester Rochester Minnesota United States 55905

Sponsors and Collaborators

  • Mayo Clinic

Investigators

  • Principal Investigator: Fernando C Fervenza, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Fernando Fervenza, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT04868838
Other Study ID Numbers:
  • 20-010520
First Posted:
May 3, 2021
Last Update Posted:
May 25, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 25, 2022