Daratumumab for Treatment of Proliferative Glomerulonephritis With Monoclonal Immune Deposits

NCT05654506 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-002587
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this research is to study the safety and efficacy of daratumumab in inducing complete or partial remission in people with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID).

Conditions

Proliferative Glomerulonephritis With Monoclonal IgG Deposits

Outcome Measures

Primary Outcomes (1)

• Change in proteinuria

  Change in protein in the urine from baseline to 12 months of follow-up

  Baseline, 12 months

Secondary Outcomes (11)

• Number of Treatment-Emergent Adverse Events

  12 months

• Proteinuria at 6 Months

  6 months

• Serum Albumin at 6 months

  6 months

• Serum Albumin at 12 months

  12 months

• Serum Creatinine at 6 Months

  6 months

Study Arms (1)

Daratumumab treatment in PGNMID

EXPERIMENTAL

Subjects with native kidney biopsy consistent with membranoproliferative glomerulonephritis with monoclonal immunoglobulin deposits will receive daratumumab.

Drug: Daratumumab

Interventions

Daratumumab DRUG

1800 mg subcutaneous (SC) injection (total amount 15 mL) into the right/left abdominal area once weekly for 8 doses followed by once every 2 weeks for an additional 8 doses

Daratumumab treatment in PGNMID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Renal biopsy read at Mayo Clinic confirming the diagnosis of PGNMID
• Proteinuria ≥ 1000 mg over 24 hours
• Creatinine clearance ≥ 20 mL/min/SA
• Subjects able and willing to give informed consent
• For female subjects of reproductive childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously during the Treatment Period, during any dose interruptions, and for 3 months after the last dose of any component of the treatment regimen. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. This birth control method must include one highly effective form of contraception (tubal ligation, intrauterine device, hormonal \[birth control pills, injections, hormonal patches, vaginal rings, or implants\] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy
• A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to dosing.
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 3 months after receiving the last dose of any component of the treatment regimen.
• For male subjects of reproductive potential who are sexually active with females of
• reproductive potential must always use a latex or synthetic condom during the study and for 3 months after discontinuing study treatment (even after a successful vasectomy).
• Male subjects of reproductive potential must not donate sperm during the study or for 3 months after the last dose of study treatment.
• Must sign an informed consent form (ICF) or their legally acceptable representative must sign indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.

You may not qualify if:

• Pregnant or planning to become pregnant
• Seropositive for human immunodeficiency virus (HIV)
• 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).
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) will also be excluded. Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR and can be included.
• Multiple myeloma defined as \>10% plasma cells on bone marrow biopsy and M-spike \> 3 g/dL and presence of myeloma defining event (hypercalcemia, cast nephropathy, bone disease, or anemia), or plasma cells \>60% or FLC ratio of involved to uninvolved \> 100
• Abnormal clinical labs defined as: anemia with Hgb \< 8.0 g/dL, thrombocytopenia with platelet count \< 75,000, leukopenia with WBC \< 3.5, or neutropenia with ANC \< 1000, AST/ALT \> 2.5 X ULN, bilirubin \> 2 X ULN
• 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 withing the past 2 years or uncontrolled asthma of any classification. Note the participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
• Clinically significant cardiac disease including:
• Myocardial infarction within 6 months before randomization, or unstable or uncontrolled disease/condition related to cardiac dysfunction (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV)
• Uncontrolled arrythmia
• Prior or current exposure to any of the following:
• To daratumumab or other anti-CD-38 therapies (unless a re-treatment study)
• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (4)

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

University North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

NOT YET RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

daratumumab

Study Officials

• Fernando Fervenza, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Corbyn Bendtsen

CONTACT

507-284-0366; bendtsen.corbyn@mayo.edu

Nicholas Geroux

CONTACT

507-266-0956; geroux.nicholas@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 8, 2022
• First Posted: December 16, 2022
• Study Start: August 17, 2023
• Primary Completion: August 1, 2026
• Study Completion: August 1, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)