Daratumumab for Glomerulonephritis

Recruiting at 4 trial locations

Overseen By Nicholas Geroux

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Anti-CD38 therapies, MMF, others

Disqualifiers: HIV, Hepatitis B, Multiple myeloma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests daratumumab (also known as Darzalex, Darzalex SC, or Darzalex Faspro) to determine if it can safely and effectively help individuals with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) achieve remission. Remission involves reducing or eliminating the disease's signs and symptoms. Individuals diagnosed with PGNMID through a kidney biopsy and experiencing significant protein loss in their urine might be suitable for the trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop all current medications, but you cannot have taken certain immunosuppressive drugs like MMF, cyclosporine, tacrolimus, or azathioprine in the last 3 months. Low-dose prednisone for unrelated conditions is allowed.

Is there any evidence suggesting that daratumumab is likely to be safe for humans?

Research has shown that daratumumab has been tested for various conditions and is generally considered safe. One study found that patients' kidney function improved significantly without major side effects. However, some patients experienced serious reactions during administration, which can be dangerous and even life-threatening, though these are rare. The FDA has already approved daratumumab for other uses, indicating that its safety is well understood. Prospective participants should discuss any concerns with the trial team to understand how these findings might apply to them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glomerulonephritis?

Daratumumab is unique because it targets CD38, a protein found on certain immune cells, which plays a role in the inflammation and damage seen in membranoproliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Unlike standard treatments like steroids or immunosuppressants that broadly suppress the immune system, daratumumab offers a more targeted approach by depleting these problematic cells. Researchers are excited about daratumumab because it could potentially reduce kidney damage more effectively while minimizing the side effects associated with traditional treatments.

What evidence suggests that daratumumab might be an effective treatment for glomerulonephritis?

Research has shown that daratumumab, which participants in this trial will receive, may help treat certain kidney problems caused by abnormal proteins. In a study on proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID), some patients who took daratumumab experienced either complete or partial remission. Complete remission involves a significant drop in protein levels in the urine and stable kidney function, while partial remission indicates a noticeable decrease in protein levels. These results suggest that daratumumab could be effective for people with PGNMID, offering hope for better kidney health. ^{1 2 3 6 7}

Who Is on the Research Team?

Fernando Fervenza, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for people with a kidney condition called PGNMID, who have significant protein in their urine and adequate kidney function. Participants must be able to consent and follow birth control guidelines. Exclusions include pregnancy, certain infections like HIV or hepatitis B/C, recent use of specific cancer drugs without response, severe lung or heart conditions, prior daratumumab treatment, and other health issues that could interfere.

Inclusion Criteria

Agreement not to donate sperm during the study or for 3 months after the last dose of study treatment

My kidneys are working well enough (creatinine clearance rate is good).

For female subjects of reproductive childbearing potential, commitment to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously during the Treatment Period, dose interruptions, and for 3 months after the last dose of any component of the treatment regimen

Exclusion Criteria

I am unable to give my consent.

I have not received any live vaccines in the last 4 weeks.

I've been taking a low dose of prednisone or similar for a condition not related to PGNMID.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab for the treatment of PGNMID

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Maintenance of remission

Participants are monitored to maintain their remission status

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview Researchers are testing the drug Daratumumab's ability to cause complete or partial remission in patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID), focusing on its safety and effectiveness.

How Is the Trial Designed?

Group I: Daratumumab treatment in PGNMID Experimental Treatment 1 Intervention

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

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a case series of four adults with primary focal segmental glomerulosclerosis (FSGS) resistant to conventional immunosuppressive treatments, all patients responded positively to rituximab, achieving sustained remission.

A literature review identified 29 additional cases of adults with immunosuppressive-resistant FSGS treated with rituximab, resulting in an overall response rate of 58%, indicating that rituximab may be an effective treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for Adults With Multi-Drug Resistant Focal Segmental Glomerulosclerosis: A Case Series and Review of the Literature. Zhong, E., Ghadiri, S., Pai, A., et al.[2022]

In a case series of seven patients with FSGS recurrence after kidney transplantation, four pediatric patients achieved complete urinary remission with minimal proteinuria after treatment with ofatumumab (OFA) and plasmapheresis, indicating its potential efficacy.

OFA may be a valuable treatment option for managing FSGS recurrence post-transplantation, especially in cases where rituximab has not been effective, although the role of plasmapheresis complicates the assessment of OFA's direct benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant. Reynolds, BC., Lamb, A., Jones, CA., et al.[2022]

Rituximab, a chimeric monoclonal antibody targeting CD20 on B cells, shows promise in treating primary and secondary glomerulonephritis by inducing B cell apoptosis and depletion for 6-9 months, which may help reduce immune-mediated inflammation.

The review highlights the need for therapies with lower toxicity compared to traditional immunosuppressive drugs, emphasizing the potential of rituximab in managing glomerulonephritis effectively while minimizing severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of rituximab in primary and secondary glomerulonephritis]. Insalaco, M., Zanoli, L., Fatuzzo, P., et al.[2016]

Alkylating agents like cyclophosphamide and chlorambucil are more effective than conservative treatments for achieving remission in patients with membranous nephropathy, but they carry risks of serious side effects such as myelotoxicity and infections.

Rituximab, an anti-CD20 monoclonal antibody, is a safe and effective treatment for about two-thirds of patients with membranous nephropathy, particularly those with PLA2R-related disease, and its efficacy can be monitored through serological changes in anti-PLA2R antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of membranous nephropathy: time for a paradigm shift. Ruggenenti, P., Fervenza, FC., Remuzzi, G.[2022]

In a case series of six patients with treatment-refractory lupus nephritis, daratumumab treatment led to significant improvements in disease activity and kidney function over 12 months, with mean disease activity scores dropping from 10.8 to 3.6.

Five out of six patients showed marked reductions in proteinuria and serum creatinine levels, alongside favorable changes in immune markers, suggesting that daratumumab could be a promising therapy for refractory lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab monotherapy for refractory lupus nephritis. Roccatello, D., Fenoglio, R., Caniggia, I., et al.[2023]

Sequential rituximab (RTX) therapy in 250 patients with difficult-to-treat nephrotic syndrome significantly reduced relapse rates, postponing relapses by a median of 3 years for steroid-sensitive patients and 2 years for steroid-resistant patients.

While RTX therapy was effective, it was associated with a high incidence of hypogammaglobulinemia (35% of patients) and infusion reactions, highlighting the need for careful monitoring of patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential rituximab therapy sustains remission of nephrotic syndrome but carries high risk of adverse effects. Sinha, A., Mathew, G., Arushi, A., et al.[2023]

Nephrotic syndrome affects 2-7 per 100,000 children annually, with steroids achieving remission in 75-90% of cases, but some patients develop steroid-resistant forms that pose a higher risk for end-stage kidney disease.

Current treatments, including monoclonal antibodies like rituximab, have shown limited effectiveness, leading to a new proposed treatment combining rituximab with daratumumab to target a broader range of B-cell subtypes, including long-lived plasma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment. Angeletti, A., Bruschi, M., Kajana, X., et al.[2023]

Human and humanized anti-CD20 monoclonal antibodies, particularly ofatumumab and obinutuzumab, show promise in treating nephrotic proteinuria conditions that are resistant to traditional therapies like rituximab, with ofatumumab potentially being more effective at higher doses.

Current studies suggest that while standard doses of ofatumumab do not outperform rituximab in children and young adults, higher doses may be beneficial for patients unresponsive to common treatments, and the combination of obinutuzumab with other therapies like daratumumab could represent a new frontier in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New and Old Anti-CD20 Monoclonal Antibodies for Nephrotic Syndrome. Where We Are? Basu, B., Angeletti, A., Islam, B., et al.[2022]

Citations

1. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex-faspro/medical-content/darzalex-darzalex-faspro-use-in-monoclonal-gammopathy-of-renal-significance

Use in Monoclonal Gammopathy of Renal Significance Zand et al (2021) conducted a phase 2 trial to evaluate the safety and efficacy of daratumumab in patients with proliferative glomerulonephritis ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33685975/

Safety and Efficacy of Daratumumab in Patients with ... Secondary outcomes were rate of complete remission (proteinuria <500 mg/d with <15% decline in baseline eGFR) or partial remission (>50% ...

3. aetna.com aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ... FDA approval was based on the efficacy outcomes that was evaluated in an open-label, randomized, active-controlled trial (ANDROMEDA; NCT03201965). The trial ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03095118

Daratumumab in Treatment of PGNMID and C3 GN This study is an open-label phase 2 trial of the safety and efficacy of daratumumab, in the treatment of PGNMID and C3GN associated with monoclonal gammopathy.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8259683/

Safety and Efficacy of Daratumumab in Patients with ... Secondary outcomes were rate of complete remission (proteinuria <500 mg/d with <15% decline in baseline eGFR) or partial remission (>50% reduction in 24-hour ...

6. darzalexhcp.com darzalexhcp.com/

DARZALEX® (daratumumab) & DARZALEX FASPRO ... These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related ...

7. darzalex.com darzalex.com/clinical-results/

Clinical Results 91% (about 9 of 10) of patients responded to treatment with DARZALEX FASPRO ® in combination with lenalidomide and dexamethasone (DRd).