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Daratumumab to Treat Active Lupus Nephritis

Primary Purpose

Lupus Nephritis

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Daratumumab

About this trial

This is an interventional treatment trial for Lupus Nephritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Mayo Clinic in RochesterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Daratumumab

Arm Description

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).

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

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.

Improvement from proteinuria

Change in proteinuria in milligrams (mg) per 24h

Change in hematuria.

Improvement in hematuria from baseline as measured by the urinalysis

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)

Change in ds-DNA

Improvement in ds-DNA in International units per milliliter (IU/mL)

Full Information

NCT ID

NCT04868838

First Posted

April 20, 2021

Last Updated

June 13, 2023

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT04868838

Brief Title

Daratumumab to Treat 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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 20, 2021 (Actual)

Primary Completion Date

May 2024 (Anticipated)

Study Completion Date

September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lupus Nephritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Daratumumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Daratumumab

Intervention Description

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.

Primary Outcome Measure Information:

Title

Efficacy of daratumumab in inducing complete(CR) or partial(PR) renal remission in patients with active class III or IV Lupus Nephritis

Description

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

Time Frame

12 months after first infusion of Daratumumab

Title

Efficacy of daratumumab in inducing complete(CR) or partial(PR)

Description

Time Frame

12 months after first infusion of Daratumumab

Secondary Outcome Measure Information:

Title

Safety of daratumumab in patients with active class III/IV LN.

Description

Incidence of major infections defined in the development of pneumonia, grade 3 urinary tract infection/pyelonephritis, sepsis, meningitis or anemia.

Time Frame

24 months after first infusion of Daratumumab

Title

Improvement from proteinuria

Description

Change in proteinuria in milligrams (mg) per 24h

Time Frame

Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab

Title

Change in hematuria.

Description

Improvement in hematuria from baseline as measured by the urinalysis

Time Frame

Baseline,6, 12, 18 and 24 months after first infusion of Daratumumab

Title

Improvement in eGFR

Description

Time Frame

Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab

Title

Change in ds-DNA

Description

Improvement in ds-DNA in International units per milliliter (IU/mL)

Time Frame

Baseline, 6, 12, 18 and 24 months after first infusion of Daratumumab

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Amber Stanton

Phone

507-293-7259

Stanton.Amber@mayo.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Angela Reinke

Phone

507-266-1047

Reinke.Angela@mayo.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fernando C Fervenza

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amber Stanton

Phone

507-293-7259

Stanton.Amber@mayo.edu

First Name & Middle Initial & Last Name & Degree

Angela Reinke

Phone

507-266-1047

Reinke.Angela@mayo.edu

First Name & Middle Initial & Last Name & Degree

Fernando Fervenza, M.D.

First Name & Middle Initial & Last Name & Degree

Zand Ladan, M.D.

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Plan pending

Links:

URL

https://www.mayo.edu/research/clinical-trials

Description

Mayo Clinic Clinical Trials

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Daratumumab to Treat Active Lupus Nephritis

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