Daratumumab to Treat Active Lupus Nephritis

Overview

About this study

The purpose of this study is to assess the effectiveness and safety of daratumumab in inducing complete or partial remission in patients with active class III or IV (± V) lupus nephritis (LN) as measured by change in proteinuria and serum creatinine.

 

 

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age ≥ 18 years of age.
  • Diagnosis of SLE according to 2019 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 ≥ 1000 mg over 24 hours.
  • eGFR ≥ 30 ml/min/SA or creatine clearance ≥ 30ml/min/1.73m^2.
  • Adequate hematology laboratory values (Hb, ANC and platelet count) within 14 days prior to registration/Adequate bone marrow function: Per institutional guidelines.
  • Adequate liver function: Per institutional guidelines.
  • Subjects should be able to give informed consent.
  • 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/ 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.

Exclusion Criteria:

  • Pregnancy.
  • Known history of human immunodeficiency virus (HIV).
  • Abnormal liver function tests > 1.5 times upper limit of normality.
  • Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (i.e., subjects who are HBsAg negative with antibodies to total hepatitis B core antigen [antiHBc] with or without the presence of hepatitis B surface antibody [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
    • EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of HBV vaccination, do not need to be testing for HBV DNA by PCR.
  • Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
  • Clinically significant cardiac disease, including:
    • Myocardial infarction within 6 months before randomization, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV);
    • Uncontrolled cardiac arrhythmia.
  • Anemia with Hgb < 8.0 g/dL.
  • Thrombocytopenia with platelet count < 100’000.
  • Any other disease (e.g., known malignancy within the past 5 years or generally disseminated Zoster / Simplex ever or locally disseminated – skin [ more than 1 dermatome)],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.
  • Prior or current exposure to any of the following:
    • To daratumumab or other anti-CD-38 therapies;
    • Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer;
    • Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.
  • Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is < 50% of predicted normal.
  • Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
  • Unable to provide consent.
  • Patients receiving > 20 mg of oral prednisone or glucocorticoid equivalent if on corticosteroids for > 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.
  • Patients can receive ACEI or ARB while enrolled in the study, but dose adjustment is not allowed unless down titration for safety reasons.
  • Patients are allowed to be on MMF at time of enrollment but no higher than total of 2000mg/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.

Eligibility last updated 8/19/21. Questions regarding updates should be directed to the study team contact.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Fernando Fervenza, M.D., Ph.D.

Open for enrollment

Contact information:

Gabrielle Hills

(507) 266-4616

Hills.Gabrielle@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20511387

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